Correction: Homo-condensation of acetophenones toward imidazothiones

Correction for ‘Homo-condensation of acetophenones toward imidazothiones’ by Phuc Hoang Pham et al., RSC Adv., 2020, 10, 40225–40228, DOI: 10.1039/D0RA03047C.

The authors regret the omission of two references, shown below as ref. 1(a) and (b), which should have appeared as ref. 7(a) and (b).On page 40227, at the end of the paragraph which starts “With the results in hand, we proposed a possible mechanism for the annulation (Scheme 5)…” the following sentence should have been added:“It should be noted that Asinger and co-workers reported a similar transformation using ammonia, instead of ammonium acetate, that occurred in methanol solvent.¹ For that reason, an alternative mechanism should not be excluded.”The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

ASSOCIATION BETWEEN PRE-STROKE PHYSICAL ACTIVITY AND MOBILITY AND WALKING ABILITY IN THE EARLY SUBACUTE PHASE: A REGISTRY-BASED STUDY

ObjectiveTo investigate associations between prestroke physical activity and mobility, walking ability, and self-perceived upper extremity function during stroke unit care.DesignA longitudinal, registry-based study with a consecutively collected cohort.Subjects/patientsA total of 1,092 adults with stroke admitted to 3 Swedish stroke units between 2017 and 2018.MethodsLogistic mixed effects regression models were performed to investigate associations (adjusted for age and sex). Pre-stroke physical activity was assessed with Saltin-Grimby Physical Activity Level Scale on admission. Mobility, walking ability, and self-perceived upper extremity function were assessed at admission and discharge from the stroke units and compared between pre-stroke physically active (45%) and inactive (55%) groups.ResultsAll groups of patients showed improvements in mobility (p < 0.001), walking ability (p < 0.001), and upper extremity function (p < 0.001). The changes over time tended to differ between the physically inactive and active groups for mobility (p < 0.062) and walking ability (p < 0.056), but the differences were not significant.ConclusionPre-stroke physically active people showed a tendency to be more independent in physical functioning early after stroke. Regardless of prestroke physical activity, all patients showed improvements in mobility, walking ability, and self-perceived upper extremity function during inpatient care.LAY ABSTRACTTo be physically active prior to a stroke may improve the post-stroke recovery process. Therefore, we hypothesized that pre-stroke physical activity might reduce the consequences of a stroke. This study investigated associations between pre-stroke physical activity and post-stroke recovery of mobility, walking ability, and arm and hand function. A total of 1,092 patients were examined; 44% were women, 89% had ischaemic stroke, and 55% were physically inactive before the stroke. All patients showed improvements during care at the stroke units, regardless of their previous physical activity level. At hospital discharge, 71% of patients showed independent mobility, 68% could walk independently, and 55% reported self-perceived arm and hand impairments. Patients with higher pre-stroke physical activity levels had a tendency of being more independent in mobility and walking compared with inactive patients. However, the frequencies of self-perceived arm and hand impairments were similar between the physically active and physically inactive groups. To be physically active prior to a stroke may improve the post-stroke recovery process.Key words: prestroke, stroke, exercise, physical activity, mobility, transfers, walking, upper extremity

The number of people living with the consequences of a stroke has increased over time (1), which has substantially increased the global burden of adult disability (2). The overall goal of stroke rehabilitation is to regain independence (2), but it has been shown that 43% have remaining disability one month after stroke, and 39% after 5 years (3). Recovery can be defined as an improvement over time, evaluated as the return to pre-stroke functions and activities, or alternatively, evaluated in terms of the underlying mechanisms (4). Agreed definitions of phases in stroke recovery are acute (1–7 days), early (7 days to 3 months), and late (3–6 months) subacute, and chronic (more than 6 months) (4). Improvements mainly occur in the early subacute phase after a stroke (4), and care at a stroke unit is important for positive outcomes (5). Stroke-unit care and rehabilitation increases the probability that patients will survive, return to their own homes, and regain independence (5) at one year post-stroke (6). In stroke rehabilitation research, stroke-related impairments (sensorimotor deficiencies, quality of life, and global disability) should be evaluated with measures capturing mobility, walking, and motor function (7). According to the International Classification of Functioning, Disability, and Health (ICF) (8), mobility and walking ability are categorized as “activities and participation”, and upper extremity (UE) function is included in the category of “body structures”.Pre-stroke physical activity may promote neuroprotective mechanisms, such as angiogenesis, and neuroplasticity, in both human and animal subjects (9). This could contribute to better motor function, and motor recovery (9). Previous studies have shown that physical activity could reduce the risk of stroke by 25–30% (10). Physical activity is defined as any bodily movement produced by skeletal muscles that requires energy expenditure (11). Different types of physical activity can be categorized as occupational, sports, conditioning, household, or other activities (11). Exercise, which is a subcategory of physical activity, is planned, structured, and repetitive, and its purpose is to improve or maintain physical fitness (11). Pre-stroke physical activity was previously related to a reduction in the size of a cerebral infarction (12), less severe acute stroke symptoms (12–15), less post-stroke disability (12, 15, 16), and improved performance in activities of daily living (ADL) (15, 17, 18). Previous studies on disability after stroke often included a mobility assessment, but, typically, mobility was not measured separately from other abilities. Moreover, few studies have focused on associations between pre-stroke physical activity and post-stroke physical functioning (19) (i.e. mobility, walking ability, and UE function). However, 3 small studies showed that pre-stroke physical activity was positively related to post-stroke improvements in balance, walking speed (17), independent gait (20), and walking frequency (21). No studies have investigated the association between pre-stroke physical activity and UE function. Overall, little evidence is available on associations between pre-stroke physical activity and different post-stroke consequences, and the published results are conflicting (19, 22). The current study aimed to investigate associations between pre-stroke physical activity and post-stroke mobility, walking ability, and self-perceived UE function during inpatient stroke unit care.     

Synthesis of novel 1,2,4-thiadiazinane 1,1-dioxides via three component SuFEx type reaction

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors. The β-aminoethane sulfonamides were obtained through sequential Michael addition of amines to α,β-unsaturated ethenesulfonyl fluorides followed by further DBU mediated sulfur(vi) fluoride exchange (SuFEx) reaction with amines at the S–F bond.

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors.

The 1,2,4-thiadiazinane 1,1-dioxide motif can be found in many biologically active compounds for vastly different medical conditions. For example, verubecestat (1) has been in phase III clinical trials as a β-amyloid precursor protein cleaving enzyme (BACE 1) inhibitor to treat moderate and prodromal Alzheimer''s disease.¹ Ribizzi et al. have shown that taurolidine (2) displays cytotoxic activity against certain human tumour cells,² but primarily it is used as an antibacterial agent.³ In addition, benzothiadiazines (3) are patented as ATP-sensitive potassium channel modulators for the treatment of respiratory, central nervous, and endocrine system disorders.⁴ 1,2,4-Thiadiazinane 1,1-dioxides of this type may be formed by various methods;^5–13 most closely related to the present work is the [2 + 2 + 2] sulfa Staudinger cycloaddition of sulfonylchlorides and imines, in which case β-sultams may also be formed through the corresponding [2 + 2] cycloaddition.^14,15 α,β-Unsaturated sulfonyl fluorides 4 are so far rarely encountered as starting materials for organic synthesis.^16–18 The literature on this reagent describe it as a connector molecule,¹⁹ and a warhead in chemical biology.^20–22 There are only four publications that, so far, have reported the use of α,β-unsaturated sulfonyl fluoride based compounds as starting materials in organic synthesis.^23–26 Based on our earlier experience with the reactivity of aryl α,β-unsaturated sulfonyl fluoride towards various amine nucleophiles¹⁷ (Scheme 1), we hypothesized that an α,β-unsaturated sulfonyl fluoride of type 4 can possibly be explored for the synthesis of thiadiazinanes. This hypothesis was based on observation of low amounts of the six-membered product was formed along with the major β-sultam product 5 when p-nitrophenylethenesulfonyl fluoride was subjected to excess methyl amine in methylene chloride as a solvent and triethylamine as additional base at room temperature (Scheme 1).Open in a separate windowScheme 1Formation of 1,2,4-thiadiazinane 1,1-dioxides, along with β-sultams, when aryl ethenesulfonyl fluorides are subjected to large excess of primary amines in DCM as solvent and DBU as catalyst.The reactivity of dichloromethane (DCM) as a methylene donor was unfamiliar to us at the time, but a literature survey quickly revealed that organic solvents (DMF,²⁷ DMSO,^28–30 CHCl₃ (ref. 31 and 32) and CH₂Cl₂ (ref. 33 and 34)) have proved to be more than solvents. DCM has indeed been reported to act as a bis-electrophilic methylene donor in the presence of strong bases and nucleophiles³³ (e.g. carboxylic acids,³⁵ thiols,³⁶ amines, etc.). DCM may also form hydrochloride salts,³⁷ aminals,³⁸ and quaternary salts³⁹ when reacted with tertiary and secondary amines. These reactions were reviewed by Mills et al.⁴⁰ and the kinetics of the reaction of DCM with pyridine was documented by Rudine et al.⁴¹ Liu and co-workers reported formation of methylene-bridged 3,3′-bis-(oxazolidin-2-one) through reaction of oxazolidin-2-ones with DCM and sodium hydride.⁴² Cui et al. reported the synthesis of bispidine with the utilisation of DCM as a C1 unit.⁴³ Dipyrrolidylmethane CH₂(pyr)₂ and dipiperidylmethane, CH₂(pip)₂ were synthesized via the condensation of the secondary amine precursors and DCM at room temperature in the absence of light.⁴⁴ Another reaction of amines with methylene chloride yielded aminals rapidly.⁴⁵ Matsumoto et al. reported the reaction of DCM with ketones or esters in the presence of secondary amines at high pressure whereby DCM was used as methylene bridge in forming both C–C and C–N bonds.⁴⁶ Zhang and co-workers also published the formation of simultaneous carbon–carbon bond and carbon-nitrogen bonds whereby DCM acted as a synthon in the presence of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and a copper catalyst.⁴⁷     

EARLY BRAIN IMAGING PREDICTORS OF POST-STROKE SPASTICITY

BackgroundPost-stroke spasticity is a major factor disturbing rehabilitation and functional recovery in stroke survivors. Clinical predictors of post-stroke spasticity have often been discussed, but brain image predictors for spasticity have been insufficiently researched. The aim of this study was to use magnetic resonance imaging data to identify early brain imaging predictors for potential development of spasticity after stroke.MethodsConsecutive patients admitted to a stroke unit were screened prospectively over 22 months. Patients with first-ever supratentorial ischaemic stroke were included in the study. Standardized clinical assessments for post-stroke spasticity were prospectively performed within 7 days and at 3 months. Brain imaging data (3 Tesla magnetic resonance imaging (3T MRI)) were collected at the baseline and evaluated.ResultsBrain imaging data from 103 stroke patients were collected in the hyperacute phase (< 7 days after stroke onset). A total of 23 patients developed post-stroke spasticity. The volumes of brain lesions involving motor network areas were significantly larger in patients with post-stroke spasticity compared with those without post-stroke spasticity (p < 0.01). Supratentorial lesion of < 0.5 cm³ were not associated with risk of post-stroke spasticity, except when the internal capsule and striatum was affected.ConclusionLesions involving motor network areas are considered to be a precondition of post-stroke spasticity. There is, however, a low risk of developing post-stroke spasticity with < 0.5 cm³ volumes of supratentorial brain lesions involving motor network areas. Larger volume brain lesions involving motor network areas, e.g. > 3 cm³, were significantly more common in patients with post-stroke spasticity. Pure cortical lesions has no risk of post-stroke spasticity in stroke survivors.LAY ABSTRACTPost-stroke spasticity is a major factor disturbing rehabilitation and functional recovery in stroke survivors. However, few studies have examined brain imaging predictors of post-stroke spasticity. Among patients with first-ever supratentorial ischaemic stroke, association between developing post-stroke spasticity, lesion site and lesion size were analysed in this prospective study. Every patient was clinically evaluated at baseline (7 days) and at 3 months. In magnetic resonance imaging (MRI) of the brain, small brain lesion volumes (< 0.5 cm³) were found to be associated with a low risk of developing post-stroke spasticity in patients with stroke. Larger lesion sizes (> 3 cm³) were significantly more common in patients with post-stroke spasticity and can be a positive predictor of post-stroke spasticity.Key words: spasticity, stroke, predictor

The earlier the complications of stroke are identified, the greater is the likelihood that patients will avoid secondary and tertiary complications, and the better their prognosis. Therefore the earlier the risk of development of post-stroke spasticity (PSS) is predicted or detected after a stroke, as one of the “plus symptom” following stroke, the more responsive patient management can be to avoid complications and improve prognosis (1, 2). If severe PSS is not managed early it will impair functional activity in affected patients, through complications, e.g. muscle shortening, contractures, pressure sores, additional to the PSS itself (1–5).Likewise, complications of PSS can lead to severe changes within a short period of time, even within a few weeks or months. If during this period PSS is not appropriately managed or treated, this, together with its complications, may detrimentally impact on patients’ physical posture, and positioning of affected joints, and thus their active freedom of movement (1, 6, 7). At a later stage, restriction in passive range of motion (ROM), hardening, or even contractures of the joint capsule may occur, which often prove irreversible in their final stage, so that surgical interventions have to be considered (8).The definition of spasticity, by Lance in 1980 (9), as a velocity-dependent increase in muscle tone, represents only one “positive” component of the upper motor neuron syndrome (UMNS), but more recent definitions include all positive symptoms (increased tendon reflexes, Babinski group reflexes, clonus, spasm, spastic dystonia and velocity-dependent increase in muscle tone) as spasticity (10), while excluding the “negative” components of the UMNS (e.g. paresis) and the complications of the UMNS (e.g. contractures, loss of muscle fibres).The pathogenesis of PSS is incompletely understood, thus only symptomatic therapies have been studied and suggested. Therefore the difficulty of management of PSS comes from detecting it at an early stage. It frequently develops gradually, building up with time, and fully manifests itself after weeks and months (11–14).Therefore, it is essential to find predictors, or their “red flags”, which indicate the potential development of spasticity with a high probability at early stages following stroke. Using such predictors, patients could be identified early following stroke and managed or treated with an appropriate approach (1, 2, 8, 11).To date, a number of studies have discussed clinical predictors for subsequent stroke-associated spasticity. Those studies include clinical predictors, such as poor functional status in the acute phase (low Barthel Index, higher modified Rankin scale, severe affected functions of the limbs), severe paresis, sensitivity loss to sensory stimuli, and young patient age (3, 12, 13, 15–17). These clinical predictors, which are associated with severe paresis and functional disorders, imply that certain locations and the size of brain lesions may be good predictors of developing PSS.Clinical predictors are considered to be an important and effective approach for the prediction of PSS (11– 13); however, the performance of clinical assessments, which are needed in order to predict more accurately, can often be limited in the hyperacute or acute phases following stroke, due to individual and clinical limitation. Therefore, analysis of brain imaging, which is a routine procedure in stroke evaluation, will be a good additional option for predicting early risk of development of PSS.There are a few studies that have investigated early brain imaging predictors of spasticity following stroke, and have suggested large volume and multiple lesion locations as possible brain imaging predictors of PSS in stroke survivors (18–23). However, these studies have suggested larger or extensive lesions as possible predictors with no mention of cut-off values for lesion size, and have suggested various possible lesion sites in the brain.The current study analysed 3 Tesla magnetic resonance imaging (3T MRI) data in order to identify early brain imaging predictors for potential development of spasticity after stroke, such as the sites and “red flags” values (sizes) of brain lesions. Patients admitted to a stroke unit were prospectively clinically examined in the acute stage (within 7 days of stroke onset) and at 3 months, for the occurrence of PSS, and MRI findings were analysed to correlate with clinical data.     

EFFECTS OF VIRTUAL REALITY-BASED NECK-SPECIFIC SENSORIMOTORTRAINING IN PATIENTS WITH CHRONIC NECK PAIN: A RANDOMIZED CONTROLLED PILOT TRIAL

ObjectiveTo evaluate the effects of neck-specific sensorimotor training using a virtual reality device compared with 2 standard rehabilitation programmes: with, and without general sensorimotor training, in patients with non-traumatic chronic neck pain.DesignPilot randomized control study.Patients and methodsA total of 51 participants were randomly assigned to 1 of 3 groups: 1: control group; 2: sensorimotor group; 3: virtual reality group. All 3 groups received the clinic’s standard rehabilitation programme. Group 2 also received “general sensorimotor training” in the form of group therapy, for a total of 120 min. Group 3 received additional virtual reality-based “neck-specific sensorimotor training” for a total of 120 min. Participants’ neck pain, headaches, active cervical range of motion, and Neck Disability Index were determined before and after 3 weeks of intervention.ResultsCompared with the control group, the virtual reality group showed significant (p < 0.05) advantages in relief of headaches, and active cervical range of motion in flexion and extension. Compared with the sensorimotor group, the virtual reality group showed significant improvements in cervical extension.ConclusionVirtual reality-based sensorimotor training may increase the effects of a standard rehabilitation programme for patients with non-traumatic chronic neck pain, especially active cervical range of motion in extension.LAY ABSTRACTThe aim of this study was to evaluate the effectiveness of neck-specific coordination training using a virtual reality device, in comparison with general coordination training and a standard exercise programme as part of inpatient rehabilitation for patients with chronic neck pain. Pain, disability and mobility of the neck were determined before and after 3 weeks of training intervention in 51 patients. The virtual reality training group exhibited greater effects in relief of headaches, and bending the neck forwards and backwards compared with the standard exercise group, and an increased ability to bend the neck backwards compared with the coordination training group. The results suggest that neck-specific coordination training using a virtual reality device increases the benefits of standard inpatient rehabilitation in patients with chronic neck pain, particularly in bending the neck backwards.Key words: neck pain, rehabilitation, virtual reality, kinematics

Neck pain is a widespread problem; 60–80% of individuals develop neck pain during their life-time, with 30–50% of the general population reporting neck pain annually (1–3). Many patients experience neck pain as a complex biopsychosocial disorder, with problematic physical and psychological symptoms (3), such as reduced cervical range of motion, headaches, lack of concentration, emotional and cognitive disorders (4, 5). Aside from the decreased quality of life, these complaints are a major cause of inability to work (6, 7) and lead to considerable economic damage (8). Hence, the demand for an effective treatment is indisputable.According to a recently published review (9), the strongest treatment effects for neck pain are those associated with exercise. However, the evidence for this claim is only of moderate quality. Since there is no data available at present to show that any one form of exercise is evidentially more effective than another, multimodal care is concordantly recommended by leading experts (3, 9).Sensorimotor training methods are a current trend in exercise therapy, and for the first time they take into account the special function of the neck, by including connections between the perceptions of sensory organs located in the head and neck muscles (10–14). Alterations of sensorimotor control have been identified in many patients with neck pain, and are thought to play an important role in the aetiology and maintenance of associated disorders (14, 15).To date, there are only a few sensorimotor training concepts that have been specially developed for the neck region. Initial studies found that patients undergoing these training methods experienced reduced neck pain, as well as improvements in cervical range of motion, self-reported disability, and general health (11, 13, 14, 16). However, a systematic review from 2014 (17) revealed very little evidence for eye-neck coordination and proprioceptive exercises. Furthermore, a randomized controlled trial (RCT) found that neck coordination exercises did not produce a larger effect than strength training and massages (18).Application of a virtual reality (VR) device is a novel and promising option for training cervical kinematics (10, 12, 19). In theory, this technique provides several advantages: distracting attention and therefore reducing pain and kinesiophobia (20, 21), engaging and motivating physical activities, and improving the effectiveness of exercise (22, 23).To date, only one RCT has compared the effects of VR-based training with conventional kinematic training using laser beams in patients with chronic neck pain (12). The VR group exhibited significant improvements in motion velocity, pain intensity, health status, and accuracy of neck motion.Due to the conflicting evidence and lack of research, there is a need for more studies that consider the effectiveness of VR-based sensorimotor training concepts, especially in combination with other effective therapeutic exercises or as part of individually tailored programmes (12).The aim of this study was therefore to evaluate the effects of neck-specific sensorimotor training using a VR device, in comparison with standard rehabilitation programmes, both with and without general sensorimotor training, in patients with non-traumatic chronic neck pain.     

Preparation of Ni-microsphere and Cu-MOF using aspartic acid as coordinating ligand and study of their catalytic properties in Stille and sulfoxidation reactions

In this study, the thermal and catalytic behavior of Ni-microsphere and Cu-MOF were investigated with aspartic acid as the coordinating ligand with different morphologies. The Ni-microsphere and Cu-MOF with aspartic acid, as the coordinating ligand, were prepared via a solvothermal method. The morphology and porosity of the obtained Ni microsphere and Cu-MOF were characterized by XRD, FTIR, TGA, DSC, BET and SEM techniques. The catalytic activity of the Ni-microsphere and Cu-MOF was examined in Stille and sulfoxidation reactions. The Ni microsphere and Cu-MOF were easily isolated from the reaction mixtures by simple filtration and then recycled four times without any reduction of catalytic efficiency.

In this study, the thermal and catalytic behavior of Ni-microsphere and Cu-MOF were investigated with aspartic acid as the coordinating ligand with different morphologies.

Cross-coupling reaction is one of the most significant methods to create carbon–carbon bonds in organic synthesis. There are many approaches, including, Suzuki, Stille, and Sonogashira cross-coupling reactions, which are well recognized and highly applicable in organic synthesis. Among them, the Stille reaction, which is an increasingly versatile tool for the formation of carbon–carbon bonds, involves the coupling of aryl halides with organotin reagents.¹ However, these reactions generally require expensive transition metal catalysts such as Pd.² Therefore, it is necessary to develop a new economic, green, and efficient methodology to reduce the environmental impact of the reaction. They are also important intermediates in organic chemistry and have been widely used as ligands in catalysis. The direct oxidation of sulfides is an important method in organic chemistry. Besides, they are also valuable synthetic intermediates for the construction of chemically and biologically important molecules, which usually synthesized by transition metal complexes.³ In this regard, different transition metal complexes of mercury(ii) oxide/iodine,⁴ oxo(salen) chromium(v),⁵ rhenium(v) oxo,⁶ H₅IO₆/FeCl₃,⁷ Na₂WO₄/C₆H₅PO₃H₂,⁸ chlorites and bromites,⁹ NBS¹⁰etc. have been introduced as catalysts. However, these catalysts have several drawbacks; including, separation problems from the reaction medium, harsh reaction conditions, and generating a lot of waste. In order to solve these drawbacks, of separation and isolation of expensive homogeneous catalysts is the heterogenization of homogeneous catalysts and generation of a new heterogeneous catalytic system. Metal–organic frameworks (MOFs) are a class of porous crystalline materials, which show great advantages, i.e. their enormous structural and chemical diversity in terms of high surface area,^11,12 pore volumes,¹³ high thermal,¹⁴ and chemical stabilities,¹⁵ various pore dimensions/topologies, and capabilities to be designed and modified after preparation.¹⁶ In this sense, it is worth mentioning that these features would result in viewing these solids as suitable heterogeneous catalysts for organic transformations.^17–22 MOFs materials are prepared using metal ions (or clusters) and organic ligands in solutions (i.e. solvothermal or hydrothermal synthesis). MOF structures are affected by metal and organic ligands, leading to have more than 20 000 different MOFs with the largest pore aperture (98 Å) and lowest density (0.13 g cm⁻³).²³ Generally, surface area and pore properties of MOFs seem quite dependent on their metal and ligand type as well as synthesis conditions and the applied post-synthesis modifications. The largest surface area was measured in Al-MOF (1323.67 m² g⁻¹)^24,25 followed by ZIF-8-MOF (1039.09 m² g⁻¹),²⁶ while the lowest value was with Zn-MOF (0.86 m² g⁻¹),²⁷ followed by γ-CD-MOF (1.18 m² g⁻¹)²⁸ and Fe₃O(BDC)₃ (7.6 m² g⁻¹).²⁹ Microspheres are either microcapsule or monolithic particles, with diameters in the range (typically from 1 μm to 1000 μm),²⁹ depending on the encapsulation of active drug moieties. In this regard, there are two types of microspheres: microcapsules, defined, as spherical particles in the size range of about 50 nm to 2 mm and micro matrices.³⁰ Microsphere structures have recently attracted much attention due to their unique properties, such as large surface area,³¹ which make them suitable for tissue regenerative medicine,³²i.e. as cell culture scaffolds,³³ drug-controlled release carriers³⁴ and heterogeneous catalysis.³⁵ Many chemical synthetic methods has been developed for their synthesis, including seed swelling,³⁶ hydrothermal or solvothermal methods,³⁶ polymerization,³⁷ spray drying³⁸ and phase separation.³⁹ Among these methods, the solvothermal synthesis has been used as the most suitable methodology to prepare a variety of nanostructural materials, such as wire, rod,⁴⁰ fiber,⁴¹ mof⁴² and microsphere.⁴³ In this sense, the synthesis process involves the use of a solvent under unusual conditions of high pressure and high temperature.⁴⁴ The properties of microspheres are highly dependent on the number of pores, pore diameter and structure of pore.⁴⁵ The degree of porosity depends on various factors such as temperature, pH, stirring speed, type, and concentration of porogen, polymer, and its concentration.⁴⁶ There have been numerous studies to investigate the coordination behavior of a ligand with different metals under the same conditions.^47–49 Herein, we aim at comparing the catalytic behavior of Ni-microsphere and Cu-MOF with aspartic acid as the coordinating ligand in Stille and sulfoxidation reactions (Scheme 1).Open in a separate windowScheme 1(a) Schematic synthesis of Ni microsphere and Cu-MOF and their application as catalyst (b) topological structure of Cu-MOF (c) topological of Ni microsphere.     

TEMPORAL EVOLUTION AND PREDICTORS OF SUBJECTIVE COGNITIVE COMPLAINTS UP TO 4 YEARS AFTER STROKE

ObjectiveTo examine the temporal evolution of subjective cognitive complaints in the long-term after stroke, and to identify predictors of long-term subjective cognitive complaints.MethodsProspective cohort study including 395 stroke patients. Subjective cognitive complaints were assessed at 2 months, 6 months and 4 years post-stroke, using the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24). The temporal evolution of subjective cognitive complaints was described using multilevel growth modelling. Associations between CLCE-24 cognition score at 4 years post-stroke and baseline characteristics, depression, anxiety, cognitive test performance, and adaptive and maladaptive psychological factors were examined. Significant predictors were entered in a multivariate multilevel model.ResultsA significant increase in subjective cognitive complaints from 2 months up to 4 years (mean 3.7 years, standard deviation (SD) 0.6 years) post-stroke was observed (p≤0.001). Two months post-stroke, 76% of patients reported at least one cognitive complaint, 72% at 6 months, and 89% at 4 years post-stroke. A higher level of subjective cognitive complaints at 2 months and lower scores on adaptive and maladaptive psychological factors were significant independent predictors of a higher level of subjective cognitive complaints at 4 years post-stroke.ConclusionPost-stroke subjective cognitive complaints increase over time and can be predicted by the extent of subjective cognitive complaints and the presence of adaptive and maladaptive psychological factors in the early phases after stroke.LAY ABSTRACTMany people suffer a stroke in the brain leading to consequences in different areas of functioning. Complaints in the domain of thinking (memory, attention, planning and organization) are frequent post-stroke. This study investigated the occurrence and type of complaints experienced in the first years after a stroke. The study found that these complaints increase over time. Longterm complaints are found in those people who already have problems early after stroke.Key words: stroke, rehabilitation, cognition, cognitive complaints

Subjective cognitive complaints (SCC) are common after stroke, with prevalence rates varying between 28.6% (1) and 90.2%, (2), depending on stroke characteristics, time since stroke, SCC definitions and the instruments used. The most commonly reported complaints are mental slowness (in 46–80% of patients) and difficulties in concentration and memory (in 38–68% and 38–94% of patients, respectively) (3). Previous cross-sectional studies showed that SCC are present in both the early stages after stroke (1–6 months after stroke) (4–6), and in the long-term (> 1 year after stroke) (1, 7, 8). To date only a few studies have examined the temporal evolution of SCC. Tinson & Lincoln observed an increase in SCC between 1 and 7 months post-stroke (n = 95) (9). The authors used the Everyday Memory Questionnaire (10), focusing on memory-related complaints. Wilz & Barskova also found an increase in SCC over time after stroke (3 vs 15 months post-stroke, n = 81) (11). SCC were measured with the Patient Competency Rating Scale cognition subscale (12). Van Rijsbergen et al., who used the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24) (13), recently found that SCC remained stable between 3 and 12 months after stroke (n = 155) (14). Long-term results on the course of post-stroke SCC are lacking. Since SCC were found to be independently related to lower quality of life in patients with mild cognitive impairment (15), and patients with subarachnoid haemorrhage (16), it is important to assess SCC after stroke. Furthermore, earlier research showed that SCC were most strongly associated with participation after stroke, compared with cognitive tests in a neuropsychological test battery, and the Montreal Cognitive Assessment (MoCA) (17, 18). Hence, in order to improve participation and integration in society after stroke, it is important to take the patients’ perspective into account, rather than only determining objective cognitive measures.The presence and severity of SCC is expected to be a direct reflection of the presence and severity of cognitive deficits. However, previous studies investigating the relationship between SCC and cognitive performance in stroke patients have shown conflicting results (1–4, 7, 8, 13, 19, 20). Other factors have shown to be related to SCC, in particular psychological factors, such as depressive symptoms (2, 4, 6, 7, 21), anxiety (21, 22), perceived stress (14), personality traits (7, 22), and coping style (23). To date, only one study on SCC used a longitudinal design (14), which prevents conclusions on the temporal evolution of SCC in stroke patients in the long term. Since more stroke patients survive, recover well and are discharged home nowadays, it is important to address predictors of SCC in the early phases after stroke, in order to identify patients who need more intensive monitoring at follow-up. Once identified, it is possible to investigate whether the patients will benefit from more focused rehabilitation programmes.The aim of this longitudinal study was to examine the temporal evolution of SCC, from 2 months until 4 years post-stroke. Furthermore, the study assessed which factors are predictive of SCC at 4 years post-stroke, taking into account demographic and stroke-related characteristics at baseline, and cognitive deficits and psychological factors measured at 2 months post-stroke.     

Synthesis of novel benzopyran-connected pyrimidine and pyrazole derivatives via a green method using Cu(ii)-tyrosinase enzyme catalyst as potential larvicidal,antifeedant activities

A series of benzopyran-connected pyrimidine (1a–g) and benzopyran-connected pyrazole (2a–i) derivatives were synthesized via Biginelli reaction using a green chemistry approach. Cu(ii)-tyrosinase was used as a catalyst in the synthesis of compounds 1a–g and 2a–ivia the Biginelli reaction. The as-synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopy, and elemental analysis. The as-synthesized compounds were screened for larvicidal and antifeedant activities. The larvicidal activity was evaluated using the mosquito species Culex quinquefasciatus, and the antifeedant activity was evaluated using the fishes of Oreochromis mossambicus. The compounds 2a–i demonstrated lethal effects, killing 50% of second instar mosquito larvae when their LD₅₀ values were 44.17, 34.96, 45.29, 45.28, 75.96, and 28.99 μg mL⁻¹, respectively. Molecular docking studies were used for analysis based on the binding ability of an odorant binding protein (OBP) of Culex quinquefasciatus with compound 2h (binding energy = −6.12 kcal mol⁻¹) and compound 1g (binding energy = −5.79 kcal mol⁻¹). Therefore, the proposed target compounds were synthesized via a green method using Cu(ii)-enzyme as a catalyst to give high yield (94%). In biological screening, benzopyran-connected pyrazole (2h) was highly active compared with benzopyran-connected pyrimidine (1a–g) series in terms of larivicidal activity.

Cu(ii)-tyrosinase catalytic help with the synthesis of benzopyran-connected pyrimidine and pyrazole derivatives and their larvicidal activity.

Benzopyrans (coumarins) are an important group of naturally occurring compounds widely distributed in the plant kingdom and have been produced synthetically for many years for commercial uses.¹ In addition, these core compounds are used as fragrant additives in food and cosmetics.² The commercial applications of coumarins include dispersed fluorescent brightening agents and as dyes for tuning lasers.³ Some important biologically active natural benzopyran (coumarin) derivatives are shown in Fig. 1. Mosquitoes are the vectors for a large number of human pathogens compared to other groups of arthropods.⁴ Their uncontrollable breeding poses a serious threat to the modern humanity. Every year, more than 500 million people are severely affected by malaria. The mosquito larvicide is an insecticide that is specially targeted against the larval life stage of a mosquito. Particularly, the compound bergapten (Fig. 1), which shows the standard of larivicidal activity,⁵ is commercially available, and it was used as a control in this study for larvicidal screening. Moreover, the antifeedant screening defense mechanism makes it a potential candidate for the development of eco-friendly ichthyocides. Coumarin derivatives exhibit a remarkably broad spectrum of biological activities, including antibacterial,^6,7 antifungal,^8–10 anticoagulant,¹¹ anti-inflammatory,¹² antitumor,^13,14 and anti-HIV.¹⁵Open in a separate windowFig. 1Biologically active natural benzopyran compound.Coumarin and its derivatives can be synthesized by various methods, which include the Perkin,¹⁶ Knoevenagel,¹⁷ Wittig,¹⁸ Pechmann,¹⁹ and Reformatsky reactions.Among these reactions, the Pechmann reaction is the most widely used method for the preparation of substituted coumarins since it proceeds from very simple starting materials and gives good yields of variously substituted coumarins. For example, coumarins can be prepared by using various reagents, such as H₂SO₄, POCl₃,²⁰ AlCl₃,²¹ cation exchange resins, trifluoroacetic acid,²² montmorillonite clay,²³ solid acid catalysts,²⁴ W/ZrO₂ solid acid catalyst,²⁵ chloroaluminate ionic liquid,²⁶ and Nafion-H catalyst.²⁷Keeping the above literature observations, coumarin derivatives 1a–g and 2a–i are usually prepared with the conventional method involving CuCl₂·2H₂O catalysis with using HCl additive. This reduces the yield and also increases the reaction time. To overcome this drawback, we used mushroom tyrosinase as a catalyst without any additive, a reaction condition not reported previously. The as-synthesized compounds were used for the biological screening of larvicidal and antifeedant activities (marine fish). In addition, in this study, we considered the molecular docking studies study based on previous studies for performing the binding ability of hydroxy-2-methyl-4H-pyran-4-one (the root extract of Senecio laetus Edgew) with the odorant binding protein (OBP) of Culex quinquefasciatus.²⁸     

C–P bond formation of cyclophanyl-, and aryl halides via a UV-induced photo Arbuzov reaction: a versatile portal to phosphonate-grafted scaffolds

A new versatile method for the C–P bond formation of (hetero)aryl halides with trimethyl phosphite via a UV-induced photo-Arbuzov reaction, accessing diverse phosphonate-grafted arenes, heteroarenes and co-facially stacked cyclophanes under mild reaction conditions without the need for catalyst, additives, or base is developed. The UV-induced photo-Arbuzov protocol has a wide synthetic scope with large functional group compatibility exemplified by over 30 derivatives. Besides mono-phosphonates, di- and tri-phosphonates are accessible in good to excellent yields. Mild and transition metal-free reaction conditions consolidate this method''s potential for synthesizing pharmaceutically relevant compounds and precursors of supramolecular nanostructured materials.

UV-induced C–P bond formation of aryl halides via photo Arbuzov reaction: a versatile portal to phosphonate-grafted scaffolds.

Aryl phosphonates and phosphonic acids, as an important class of organophosphorus products, have elicited enormous interest in pharmaceutical science for their biological application,^1–5 in catalysis as precursors of privileged phosphine ligands,^6–8 and in materials science as supramolecular tectons.^9–11 For the synthesis of aryl phosphonates, besides conventional Grignard or organolithium protocols, the development of the palladium-catalyzed Hirao cross-coupling of H-phosphonates with aryl halides is a convenient method,¹² and several modified protocols have been reported in recent years.^13,14Development of new and generally useful C–P bond formation methods with controlled selectivity that are widely applicable, cheap, and operationally simple have been an outstanding objective since phosphonylated products have a broad spectrum of applications. For instance, phosphono-fluoresceins due to the influence of the phosphoryl moiety insertion, show an almost 70-fold increase in intracellular brightness, compared to the analogous sulfono-, and carboxy-fluorescein, as recently reported by Miller and co-workers.² Recent trends to realize C–P bond formation are focused on visible-light-driven reactions, where Toste and co-workers first developed a dual catalytic strategy by combining gold and ruthenium photoredox catalysis for the oxidative P-arylation of H-phosphonates.¹⁵ Similarly, König and co-workers reported the ruthenium-catalyzed phosphonylation of electron-rich arenes mediated by C^Ar–H activation employing trialkyl phosphites.¹⁶ Metal-free variants using either organic dyes,^17–20 hypervalent iodine reagents,²¹ or strong base²² are additionally emerged as a useful tool to promote C–P bond formation (Fig. 1).Open in a separate windowFig. 1Selected methods previously reported for light-induced C–P bond formation.Strategies that employ trialkyl phosphites have the drawback of expensive reagents, transition metal catalysts, or large catalyst loadings. The UV-induced photo-Arbuzov reaction has mostly been neglected, even though it is more than 50 years old.^23–25 The original publication by Griffin and coworkers describes the reaction of aryl iodides with trialkyl phosphites at low temperatures (−8 to 0 °C).²⁴ The phosphonylation of aryl triflates with trialkyl phosphites via photo-induced Arbuzov-type reaction, using UV light in combination with a base as additive has recently been realized.²⁶ The need for aryl iodides and poor substrate scope foreclosed this reaction to become broadly applicable. Advancing the UV-induced photo-Arbuzov reaction for the preparation of aryl phosphonates, in this work, we report a new and more effective method for C–P bond formation under mild conditions without the need for catalysts, additives, or a base employing a wide array of functionalized aryl-, heteroaryl and thiacyclophanyl halides. The P-arylation proceeds with excellent functional group tolerance regardless of the steric hindrance and represents an important step forward in enabling C–P bond formation. Multiple and domino approach was investigated under the optimized conditions form the application perspective of the phosphonates as molecular tectons in nanostructured materials.     

Yield stress fluids and fundamental particle statistics

Yield stress in complex fluids is described by resorting to fundamental statistical mechanics for clusters with different particle occupancy numbers. Probability distribution functions are determined for canonical ensembles of volumes displaced at the incipient motion in three representative states (single, double, and multiple occupancies). The statistical average points out an effective solid fraction by which the yield stress behavior is satisfactorily described in a number of aqueous (Si₃N₄, Ca₃(PO₄)₂, ZrO₂, and TiO₂) and non-aqueous (Al₂O₃/decalin and MWCNT/PC) disperse systems. Interestingly, the only two model coefficients (maximum packing fraction and stiffness parameter) turn out to be correlated with the relevant suspension quantities. The latter relates linearly with (Young’s and bulk) mechanical moduli, whereas the former, once represented versus the Hamaker constant of two particles in a medium, returns a good linear extrapolation of the packing fraction for the simple cubic cell, here recovered within a relative error ≈ 1.3%.

Yield stress in complex fluids is described by resorting to fundamental statistical mechanics for clusters with different particle occupancy numbers.

Yield stress fluids form a particular state of matter,¹ displaying non-linear and novel visco-plasto-elastic flow dynamics upon different boundary conditions. As their name says, they don’t flow until a certain load, the so-called yield stress (or point, τ₀), is applied. This value may be generally interpreted as a shear stress threshold for the breakage of interparticle connectivity.² Furthermore, as it initiates motion in the system, it is connected to mechanical inertia³ and particle settling, i.e. it is a terse summary of buoyancy, dynamic pressure, weight, viscous and yield stress resistances.⁴ For prototype systems such as colloids dispersed in a liquid, yield points sensibly depend on the mechanism by which the solid phase tends to interact or aggregate.^5–8 The macroscopic constitutive equations they obey, such as the Herschel–Bulkley model, were shown to correspond, over a four-decade range of shear rates, to the local rheological response.⁹From the side of an experimenter, however, unambiguously defining a yield stress may not always be straightforward. It can be affected by the experimental procedure adopted, always considering a measurement or some extrapolation technique with the limit of zero shear. Conversely, unyielded domains may be defined by areas where the shear stress second invariant falls below the yield value, plus some small semi-heuristic constant.¹⁰ In addition, theoretically, the meaning of notions like τ₀ and rheological yielding were questioned to be only qualitative or even to stand for an apparent quantity.¹¹ The dependence they generally show on timescales characteristic of the applied (mechanical) disturbance, also suggested an intimate relationship¹² between yield stress and dispersion thixotropy.¹³ On the other hand, assigning a hydrodynamic or mechanical state below the yield point to a material that is not flowing seems not to be scientifically sound. Experimental values are normally obtained by extrapolation of limited data, whereas careful measurements below the yield point would actually imply that flow takes place.¹⁴At any rate, the analysis of properly defined τ₀ concepts forms the subject of interesting investigations and is still a powerful tool in many applications, including macromolecular suspensions,¹⁵ gels, colloidal gels and organogels,^16–18 foams, emulsions and soft glassy materials.¹⁹ It allows for effective comparisons between the resistances which fluids initially oppose to the shear perturbation, somehow specifying a measure of the particle aggregation states taking place in a given dispersant. Electrorheological materials, for instance, exhibit a transition from liquid-like to solid-like behaviors, which is often examined by a yield stress investigation upon a given fluid model (e.g. the Bingham model or the Casson model).^20,21 The combination of yield stress measurements with AFM techniques can be used to well-characterize the nature of weak particle attractions and surface forces at nN scales.⁸ Further issues of a more geometrical nature, which naturally connect to τ₀, are rheological percolation²² and its differences from other connectivity phenomena, such as the onset of electric²³ or elastic percolation.^24,25 In granular fluids, it relates with the theory of jammed states,²⁶ originally pioneered by Edwards.²⁷In nanoscience as well, the stability control and characterization in single and mixed dispersions or melts is an important and complex step.^28,29 Carbon nanotube suspensions,³⁰ for example, can be prepared in association with other molecular systems, like surfactants and polymers^31–33 or by (either covalent or non-covalent) functionalization of their walls with reactive groups, which increases the chemical affinity with dispersing agents.³⁴ As a consequence of large molecular aspect ratios and significant van der Waals’s attractions, the nanotube aggregation is highly enhanced, giving rise to strongly anisotropic systems of crystalline ropes and entangled network bundles, which are difficult to exfoliate, suspend or even characterize.³⁵ Stable CNT dispersions of controlled molecular mass may also exhibit polymeric behavior, and be quantitatively studied by equations taken from the well-established science of macromolecules.^36,37This paper puts forward a basic approach, mostly focused on equilibrium arguments, to devise a yield stress law connected with particle statistics. By conjecturing an ensemble of effective volumes ‘displaced’ at the incipient state of motion, a statistical mechanics picture of τ₀ is proposed. This affords a phenomenological hypothesis that can be developed with reasonable simplicity. The derived relations are applied to typical disperse systems in colloid science and soft matter, such as aqueous and nonaqueous suspensions of ceramic/metal oxides and nanoparticles.     

PREVALENCE OF DISCOMPLETE SENSORIMOTOR SPINAL CORD INJURY AS EVIDENCED BY NEUROPHYSIOLOGICAL METHODS: A CROSS-SECTIONAL STUDY

ObjectivesTo assess the prevalence of residual trans-lesion connectivity in persons with chronic clinically complete spinal cord injury (discompleteness) by neurophysiological methods.ParticipantsA total of 23 adults with chronic sensorimotor complete spinal cord injury, identified through regional registries the regional spinal cord registry of Östergötland, Sweden.MethodsDiagnosis of clinically complete spinal cord injury was verified by standardized neurological examination. Then, a neurophysiological examination was performed, comprising electroneurography, electromyography, sympathetic skin response and evoked potentials (sensory, laser and motor). Based on this assessment, a composite outcome measure, indicating either strong, possible or no evidence of discomplete spinal cord injury, was formed.ResultsStrong neurophysiological evidence of discomplete spinal cord injury was found in 17% (4/23) of participants. If also accepting “possible evidence”, the discomplete group comprised 39% (9/23). The remaining 61% showed no neurophysiological evidence of discompleteness. However, if also counting reports of subjective sensation elicited during neurophysiological testing in the absence of objective findings, 52% (12/23) showed indication of discomplete spinal cord injury.CONCLUSIONEvidence of discomplete spinal cord injury can be demonstrated using standard neurophysiological techniques in a substantial subset of individuals with clinically complete spinal cord injury. This study adds to the evidence base indicating the potential of various modes of cross-lesional sensorimotor functional restoration in some cases of chronic clinically complete spinal cord injury.LAY ABSTRACTSpinal cord injuries are usually classed as complete or incomplete. A complete injury implies that no residual function exists below the neurological level of injury. This status is determined by standardized neurological examination and is thought to correlate with spinal cord function in each individual with spinal cord injuries. However, studies have indicated that, in some people with complete spinal cord injury, there may be residual function that is not detected by such testing. The aim of the current study was to examine whether residual function, which is not detected by such testing, exists, and, if so, how common it is among people with complete spinal cord injuries (based on clinical testing) in a chronic stage (>2 years since injury). A battery of neurophysiological tests was used. Signs of “subclinical” residual function were found in 17–39% of 23 participants. This finding may lead to improvements in rehabilitative outcomes for people with complete spinal cord injury.Key words: somatosensory evoked potentials, motor evoked potentials, electromyography, sympathetic skin response, laser evoked potentials, spinal cord injury, complete, discomplete

Spinal cord injury (SCI) causes sensorimotor deficits at and below the neurological level of injury (NLI), including paralysis and altered or lost sensory function. Autonomic functions are usually also impaired to some extent, affecting respiratory, circulatory, bladder, bowel and sexual functions (1). In addition, complications such as excessive spasticity and neuropathic pain are common (2, 3) and associated with decreased quality of life (4). There is no known unambiguous correlation between the degree of neurological deficits and the presence of such complications.Currently, no methods are available in clinical routine practice for repairing SCI. However, as the concept of neuroplasticity has gained acceptance (5, 6), interest in exploring therapeutic neuro-modulation has increased.SCI is classified as complete or incomplete, using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) (7), which is based entirely on clinical sensorimotor examination. Based on the clinical assessment, SCI is sub-classified into 5 levels of varying residual infra-lesion neurological function; American Spinal Injury Association Impairment Scale (AIS) A–E (where A is complete functional transection, and E is complete restitution of infra-lesional sensory and voluntary motor function). In some individuals with SCI of grade AIS A, there exists a “zone of partial preservation” (ZPP), defined as the most caudal segment with some sensory function, determined by pin-prick and light touch testing below NLI, without sacral preservation of sensory and voluntary motor function (7, 8).A high prevalence (30–78%) of residual anatomical continuity was noted in post-mortem studies on clinically complete traumatic SCI (9, 10). It is likely that such anatomical continuity corresponds to a functional but subclinical neurological connectivity across the injury site in some cases. However, other pathways for such connectivity have also been proposed, e.g. the sympathetic trunk and/or the vagus nerve (11–14).For residual subclinical trans-lesion connectivity, the term discomplete spinal cord injury (dSCI) was proposed (15). Various methods for detection of this phenomenon have since been used, and both motor and sensory discompleteness have been proposed.For assessment of motor dSCI, electromyography (EMG) was the first method used (16). EMG recordings below the NLI can also be combined with transcranial magnetic stimulation (TMS) of the brain motor cortex (17, 18) to find signs of subclinical trans-lesion motor conduction.Sensory dSCI has been studied using somatosensoryevoked potentials (SEP, 17–19), consisting of somatosensory peripheral stimulation (typically electrical nerve stimulation) under simultaneous registration of activity in the somatosensory cortex, using scalp electrodes. Functional magnetic resonance imaging (fMRI) appears to have a higher sensitivity for detecting remaining sensory connectivity in patients with clinically complete SCI (25–54% (19–21)), compared with SEP (13–25% (22, 23)):In one study (23), 8/12 (67%) people with SCI and neuropathic pain perceived a change in perception below the NLI using adjuvant-enhanced thermal stimulation, compared with 0/12 (0%) for the group without neuropathic pain. Thus, a correlation was postulated between sensory dSCI and neuropathic pain after SCI.In summary, evidence for the concept of dSCI has accumulated. However, most of these studies have been small, and methods and quality of control conditions have varied. The current study aimed to determine the prevalence of motor and/or sensory dSCI among persons with chronic clinically complete SCI, by strict application of current clinical diagnostic criteria, and use of multiple, standardized neurophysiological methods.     

Correction: Direct electrodeposition of cationic pillar[6]arene-modified graphene oxide composite films and their host–guest inclusions for enhanced electrochemical performance

Correction for ‘Direct electrodeposition of cationic pillar[6]arene-modified graphene oxide composite films and their host–guest inclusions for enhanced electrochemical performance’ by Qunpeng Duan et al., RSC Adv., 2020, 10, 21954–21962, DOI: 10.1039/D0RA03138K.

The authors regret omitting a citation of their related paper published in Frontiers in Chemistry: ‘Facile one-step electrodeposition preparation of cationic pillar[6]arene-modified graphene films on glassy carbon electrodes for enhanced electrochemical performance’ (DOI: 10.3389/fchem.2020.00430) shown as ref. 1 here. The citation should appear as ref. 58 in the original article.¹The authors regret that it was not clear in the original article that the ErGO-CP6/GCE film had been previously reported by them in their related Frontiers in Chemistry paper¹ and therefore the sentence at the start of paragraph 3 on page 2 ‘In this work, we report for the first time preparation of CP6 functionalized graphene films on glassy carbon electrode (GCE) directly from GO-CP6 dispersions by facile one-step pulsed electrodeposition technique (Scheme 1).’ should be ‘In this work, we report the preparation of CP6 functionalized graphene films on glassy carbon electrode (GCE) directly from GO-CP6 dispersions by facile one-step pulsed electrodeposition technique (Scheme 1), which was previously reported by us.⁵⁸’.The authors also wish to clarify the differences between this RSC Advances paper and the Frontiers in Chemistry paper.¹ The papers use different guests molecules and different optimum pulse electrodeposition parameters and the RSC Advances paper reports an improvement in electrochemical performance with additional characterisation, stability studies and the analysis of real samples which are not reported in the Frontiers in Chemistry paper.¹The appropriate figure captions have been updated to reflect the data reproduced from the Frontiers in Chemistry paper.¹Scheme 1 Schematic illustration for the pulsed electrodeposition preparation of ErGO and ErGO-CP6 films on the surface of GCE and sensing the guest molecules by an electrochemical strategy. Reproduced with permission from ref. 1. Copyright 2020 Frontiers.Fig. 1 Characterization of materials. FTIR spectra (A), UV-vis absorption spectra (B), TGA curves of CP6, GO-CP6, and GO (C), and XPS survey spectra of GO and GO-CP6 (D). The data in (a, c and d) have been reproduced with permission from ref. 1. Copyright 2020 Frontiers.Fig. 4 (A) Raman spectra of GO and ErGO. (B) Raman spectra of GOCP6 and ErGO-CP6. Reproduced with permission from ref. 1. Copyright 2020 Frontiers.     

REHABILITATION IN PATIENTS WITH LYMPHOMA: AN OVERVIEW OF SYSTEMATIC REVIEWS

ObjectiveTo evaluate existing evidence from published systematic reviews for the effectiveness of rehabilitation interventions in patients with lymphoma.Data sourcesA comprehensive literature search was conducted using medical/health science databases up to 1 October 2020. Bibliographies of pertinent articles, journals and grey literature were searched.Data extraction and synthesisTwo reviewers independently selected and reviewed potential reviews for methodological quality and graded the quality of evidence for outcomes using validated tools. Any discrepancies were resolved by final group consensus.ResultsTwelve systematic reviews (n = 101 studies, 87,132 patients with lymphoma) evaluated 3 broad categories of rehabilitation interventions (physical modalities, nutrition and complementary medicine). Most reviews were of moderate-to-low methodological quality. The findings suggest: moderate-quality evidence for exercise programmes for improved fatigue and sleep disturbance; low-quality evidence for exercise therapy alone and qigong/tai chi for improved symptoms and overall quality of life, and an inverse association between sunlight/ultraviolet radiation exposure and incidence of non-Hodgkin’s lymphoma; and very low-quality evidence for beneficial effects of yoga for sleep disturbances. Association between physical activity and lymphoma risk is indistinct.ConclusionDespite a range of rehabilitation modalities used for patients with lymphoma, high-quality evidence for many is sparse. Beneficial effects of exercise programmes were noted for fatigue, psychological symptoms and quality of life. More research with robust study design is required to determine the effective rehabilitation approaches.LAY ABSTRACTLymphoma and its treatment cause significant disability and morbidity, often requiring comprehensive rehabilitation. Currently, a range of rehabilitation interventions are applied in patients with lymphoma. This review systematically evaluated evidence from published systematic reviews of clinical trials to determine the effectiveness of rehabilitation interventions in patients with lymphoma. The findings suggest that there is moderate-quality evidence for exercise programmes in improving fatigue and sleep disturbance. There was low-quality evidence for exercise therapy alone and qigong/tai chi for improved symptoms and overall quality of life, and very low-quality evidence for beneficial effects of yoga for sleep disturbances. The evidence for association of vitamin D or physical activity and lymphoma risk is limited.Key words: lymphoma, rehabilitation, systematic review, critical appraisal

Lymphomas are a heterogeneous group of malignant neoplasms of the haematopoietic system, characterized by the aberrant proliferation of mature lymphoid cells or their precursors (1). Traditionally lymphoma is classified broadly into 2 major groups: non-Hodgkin’s lymphoma (NHL, 90%) and Hodgkin’s lymphoma (HL) (1); however, lymphomas can also be stratified by cell of origin, as in the World Health Organization (WHO) classification (B-cell, T-cell/natural killer-cell (T/NK) and HL), or clinical behaviour (aggressive or indolent) (2, 3). An estimated 590,000 new cases of lymphoma (3.2% of all cancers) were diagnosed worldwide in 2018, the majority being NHLs (509,590 cases, 2.8% of all cancers) (4). NHL is a leading cause of death amongst the haematological malignancies globally, estimated to cause over 248,000 deaths (2.6% of all cancers) in 2018 (4). The incidence of lymphoma is increasing, with total worldwide incidence projected to reach approximately 919,000 by 2040 (5).The total global economic burden of lymphoma is unknown; however, treatments and supportive care requirements are resource-intensive and associated with significant financial costs for patients/families and healthcare systems. Productivity losses arise from disease and treatment-associated morbidity and premature mortality (6). In 2018, the mean monthly healthcare and utilization costs per patient for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the USA were approximately US$11,890 and $10,460, respectively (6). In Spain, in 2017 lymphoma represented 45.4% of productivity losses due to haematological malignancies, resulting in €121 million in losses due to premature mortality (7).Current therapeutic advances and cancer detection/diagnosis have improved survival rates for patients with lymphoma (PwL). The age-standardized 5-year net survival of lymphoid malignancies in adults ranges from 40% to 70% globally in 2010–14, with a 5–10% increase in trend for the period 2000–04 (8). The 5-year survival rate in the US in 2010–16 was estimated to be 72.7% for NHL and 87.4% for HL (9). As the incidence of NHL is strongly associated with increasing age, improved supportive care and availability of reduced intensity chemotherapy regimens (such as prednisone, etoposide, procarbazine, and cyclophosphamide – ‘PEP-C’; rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone – ‘R-miniCHOP’, rituximab, cyclophosphamide, vincristine, prednisolone – ‘R-CVP’) are critical to facilitate deliverable therapy to older patients. Despite these factors, certain lymphomas and their treatment are associated with short- and medium-term residual neurological deficits, leading to physical, cognitive, psychosocial and behavioural impairments, limiting activities of daily living (ADL) and participation (10–13). Treatment procedures can be extensive (e.g., radiotherapy, chemotherapy and/or surgery), and associated with a range of side-effects/complications, such as neuropathy, cardiotoxicity, cachexia, fatigue, deconditioning, myopathy, etc. (14–16). Furthermore, in the transitional period, various adjustment issues are reported, such as increased care needs, inability to drive and return to work, financial constraints, relationship stress, and limitation in societal participation (11, 14, 17, 18). Distressing symptoms, such as fatigue, is a major complaint, reported in 60–100% of patients during or after cancer treatment, which persists for several years after treatment (19–21). Therefore, patients require routine surveillance to monitor complications and relapse and integrated longer-term management, including rehabilitation (22–24).Rehabilitation is an integral part of any cancer management, and there is evidence suggesting the beneficial effect of comprehensive rehabilitation (25–31). Furthermore, a major limitation of delivery of chemotherapy and predictor of inferior outcome is poor performance status (32). As the incidence of older patients treated for lymphoma requiring rehabilitation before or after anti-lymphoma therapy increases, effective evidence-based rehabilitation strategies are expected to play critical and expanding roles in best practice. Currently, a range of rehabilitation interventions are trialled in the management of lymphoma pre-treatment, during adjuvant therapies, and late phases of care, and, for the longer-term, care continuum in the community. The aim is to maximize patient function, promote independence and participation, and improve psychological well-being and quality of life (QoL) (28, 29). Reports suggest that patients with haematological malignancies, including lymphomas, can make functional gains in inpatient rehabilitation settings (31). Maximal exercise capacity seems to decrease before treatment in PwL, especially in patients with advanced disease, and tends to return to close to normal during and/or after treatment (33). Furthermore, comprehensive exercise programmes were found to be effective in reducing disability and symptoms (depression, anxiety, fatigue, pain, etc.), improving functional capacity, muscular strength and QoL (19, 31, 34, 35). One systematic review reported that NHL survivors who met public health exercise guidelines defined by the American College of Sports Medicine (i.e. engaging in >30 min/day of at least moderate physical activity (PA) on ≥ 5 days/week, or > 150 min a week) reported a clinically important better health-related quality of life (HRQoL) than their counterparts who did not meet exercise guidelines (11). Aerobic exercise training interventions were associated with positive effects on cardiorespiratory fitness, fatigue and self-reported physical functioning, and were feasible and safe in PwL (33). Other complementary and alternative therapies, such as mindfulness-based cognitive therapy, meditation, yoga, and tai chi, have shown improvement in cognitive function and QoL (36–38). Another recent systematic review reported that a combination of PA together with mental exercise may be more beneficial to PwL (39). There remains, however, an unmet need in the cancer population, and only a limited number of survivors receive the appropriate rehabilitation intervention that they need (40, 41). Furthermore, despite acknowledging rehabilitation as an integral component of the management of cancer patients, rehabilitation-specific guidelines for many cancer groups are limited, and many general cancer guidelines do not incorporate recommendations for specific rehabilitation interventions (42–44).As mentioned above, various systematic reviews have evaluated the current evidence regarding the effectiveness and safety of different rehabilitation interventions in PwL. However, these published reviews vary in scope, methodology and quality, with diverse, and occasionally discordant, conclusions. The heterogeneity of the lymphoma rehabilitation literature warrants a comprehensive review, with a focus on the evidence for efficacy and potential harm of various rehabilitative strategies. A systematic review of systematic reviews is a new approach to synthesize current evidence across the same or similar interventions, to summarize treatment effect in a much broader concept (45). This approach allows comparison of results from multiple reviews, thereby providing a comprehensive evidence-based summary (45, 46). To our knowledge, systematic reviews of rehabilitation strategies for PwL have not been thoroughly and qualitatively appraised to date. Therefore, this review aimed to systematically evaluate existing evidence from published systematic reviews for the effectiveness of rehabilitation strategies for improved function, impairments and participation in PwL. Specific questions addressed include: Are rehabilitation interventions effective in minimizing impairment, activity limitation, participation restriction and treatment-related complications in PwL?, and: What specific types of rehabilitation interventions are effective in PwL, and in which setting?     

CLINICAL SPASTICITY ASSESSMENT USING THE MODIFIED TARDIEU SCALE DOES NOT REFLECT JOINT ANGULAR VELOCITY OR RANGE OF MOTION DURING WALKING: ASSESSMENT TOOL IMPLICATIONS

ObjectiveSpasticity assessment is often used to guide treatment decision-making. Assessment tool limitations may influence the conflicting evidence surrounding the relationship between spasticity and walking. This study investigated whether testing speeds and joint angles during a Modified Tardieu assessment matched lower-limb angular velocity and range of motion during walking.DesignObservational study.SubjectsThirty-five adults with a neurological condition and 34 assessors.MethodsThe Modified Tardieu Scale was completed. Joint angles and peak testing speed during V3 (fast) trials were compared with the same variables during walking in healthy people, at 0.40–0.59, 0.60–0.79 and 1.40–1.60 m/s. The proportion of trials in which the testing speed, start angle, and angle of muscle reaction matched the relevant joint angles and angular velocity during walking were analysed.ResultsThe Modified Tardieu Scale was completed faster than the angular velocities seen during walking in 88.7% (0.40–0.59 m/s), 78.9% (0.60– 0.79 m/s) and 56.2% (1.40–1.60 m/s) of trials. When compared with the normative dataset, 4.2%, 9.5% and 13.7% of the trials met all criteria for each respective walking speed.ConclusionWhen applied according to the standardized procedure and compared with joint angular velocity during walking, clinicians performed the Modified Tardieu Scale too quickly.LAY ABSTRACTSpasticity is an abnormal increase in muscle tightness, which is common following neurological injury. Spasticity has been shown to have a profound impact on an individual’s independence and quality of life. The main goal reported by patients in this population is to return to independent, normal walking. Yet, despite this there is a lack of consensus regarding the relationship between spasticity and walking outcomes. This may be due to a disconnect between clinical, bed-based assessment methods and how spasticity manifests during walking. This study aimed to establish how well a routine clinical assessment (the Modified Tardieu Scale) matched the speed and range of joint movement during walking. The findings suggest that, currently, clinicians performed the assessment too fast, which may lead to “false-positive” assessment findings. This may result in the identification and treatment of spasticity that is not impacting walking, leading to sub-optimal patient outcomes and significant healthcare wastage.Key words: muscle spasticity, patient outcome assessment, rehabilitation, brain injuries, gait, walking

Spasticity is a common impairment following neurological injury (1–5). The effective assessment and management of spasticity receives significant attention due to the detrimental effects it has on patient outcomes, carer burden, and quality of life (6, 7). Current spasticity guidelines recommend that only spasticity impacting function should receive intervention (8). As such, the role of a clinical assessment is to identify the presence of spasticity and decipher whether the spasticity warrants intervention, such as botulinum toxin-A (BoNT-A).Walking limitations are the most significant selfperceived, functional problem reported by individuals following neurological injury (9). A primary rehabilitation goal is often to improve walking independence, quality, speed, and endurance (10–12). In relation to spasticity, the clinician’s role is to identify whether spasticity is present, and subsequently determine if a patient’s walking may benefit from spasticity-related interventions.A definition of spasticity published by Pandyan et al. (13); “disordered sensori-motor control, resulting from an upper motor neurone lesion, presenting as intermittent or sustained involuntary activation of muscles’’, encompasses all the positive features of upper motor neurone syndrome (UMNS) under an umbrella term of spasticity. This terminology defines spasticity as a broader sensori-motor phenomenon (13), when compared with the more constrained, velocity-dependent definition published by Lance (14);”a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflexes, as one component of the UMNS” (14). For the purpose of this study, Lance’s definition has been used to define spasticity, since, with this definition, spasticity can be assessed as an individual construct. The Modified Tardieu Scale (MTS) is an often-recommended spasticity assessment, aligning with Lance’s (14) definition of spasticity (15–17). The MTS classifies the response of a relaxed muscle to a fast, passive stretch (V3). The assessment protocol involves a clinician moving the joint “as fast as possible” through its full range of motion (ROM) without specifying or measuring the speed of completion. The MTS is applied according to this standardized protocol regardless of the functional status or goals of the patient. For example, a household ambulator walking at ≤ 0.30 m/s is assessed at the same speed as a community ambulator walking at ≥ 0.80 m/s, whose muscles and joints are moving much faster when walking (18). This “one-size-fits” all approach does not take into account the variability in joint ROM and angular velocity (or speed of lowerlimb movement) with changes in walking speed (19). As such, the MTS may not sensitively discriminate individuals who have spasticity impacting their walking.While it is well established that interventions, such as BoNT-A, reduce spasticity at an impairment-based level, current treatment modalities for spasticity do not necessarily lead to improved walking outcomes (20–22). This may be because standardized protocols for scales such as the MTS do not reflect joint movement during walking (23–25). For example, if clinicians test at a speed that is slower than the joint angular velocity seen during walking, they may fail to identify spasticity that is affecting walking (i.e. false-negative). Conversely, if clinicians test at a speed that exceeds the joint angular velocity seen during walking, they may identify spasticity that is not impacting walking (i.e. false-positive).Matching the joint angles and testing speed of the MTS to the ROM and angular velocity seen during walking may assist in identifying patients who have spasticity impacting functional performance, leading to treatment decisions that optimize patient outcomes and healthcare resources. This study aimed to compare the joint start angle, angle of muscle reaction, and testing speed during a standardized MTS assessment of 4 major muscle groups of the lower-limb, collected in people with neurological conditions, with joint ROM and angular velocity in a healthy population walking at a range of speeds.     

INCREASED SATELLITE CELL APOPTOSIS IN VASTUS LATERALIS MUSCLE AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION

ObjectiveRecovery of the quadriceps femoris muscle after anterior ligament reconstruction is impaired. The aim of this study was to investigate satellite cell content and function of the vastus lateralis muscle after anterior ligament reconstruction.MethodsBiopsies were obtained from the vastus lateralis muscle of 16 recreational athletes immediately before and again 12 weeks after anterior ligament reconstruction. Total satellite cell number (Pax7⁺), activated (Pax7⁺/MyoD⁺), differentiating (Pax7^–/MyoD⁺), and apoptotic (Pax7⁺/TUNEL⁺) satellite cells, myofibers expressing myosin heavy chain (MHC) I and II, and neonatal MHC (MHCneo) were determined immunohistochemically.ResultsAfter anterior ligament reconstruction, the number of apoptotic satellite cells was significantly (p = 0.019) increased, concomitant with a significant (p < 0.001) decrease in total satellite cell number, with no change in activated and differentiating satellite cell number. MHCneo⁺ myofibers tended towards an increase.CONCLUSIONSatellite cell apoptosis and the reduction in the satellite cell pool might provide an explanation for prolonged quadriceps muscle atrophy after anterior ligament reconstruction.LAY ABSTRACTProtracted muscle atrophy is common after anterior ligament reconstruction, even if athletes adhere to a structured rehabilitation programme. Satellite cells, the stem cells of skeletal muscle, play an important role in recovery of an atrophied muscle. Exercise can activate satellite cells, induce their proliferation, and probably also differentiation of these stem cells. The current study evaluated satellite cell content and function in biopsies from the vastus lateralis muscle of 16 recreational athletes immediately before and 12 weeks after anterior ligament reconstruction. After anterior ligament reconstruction, an increased number of satellite cells showed signs of apoptosis (cell death). Furthermore, total satellite cell number was decreased, with no change in the numbers of activated and differentiating satellite cells. The number of regenerating myofibers expressing neonatal myosin tended to increase. In conclusion, satellite cell apoptosis and the reduced satellite cell number might provide an explanation for the impaired muscle recovery after anterior ligament reconstruction.Key words: satellite cells, apoptosis, muscle regeneration, developmental myosin heavy chain, muscular atrophy, quadriceps muscle

Protracted atrophy and weakness of the quadriceps muscle are common after anterior cruciate ligament (ACL) injury and/or anterior cruciate ligament reconstruction (ACL-R), even if the patients undergo guided rehabilitation programmes (1–4). Muscle recovery is compromised due to negative changes in the knee extensor muscles, most likely due to impaired neuromuscular function (5), post-surgery inflammation (6) and immobilization (7). After ACL injury, fibrogenic alterations were observed in biopsies obtained from the vastus lateralis muscle of the injured leg (8, 9). Satellite cell (SC) abundance was also reduced compared with biopsies taken from the vastus lateralis muscle of the uninjured leg (8, 10). Furthermore, there was a surprising lack of increase in SC number after regular rehabilitation training (10), as well as after 12 weeks of supervised quadriceps strength training during rehabilitation after ACL-R (3).SCs play an important role in skeletal muscle growth and regeneration (11, 12). Increases in SC number occur after 11–12 weeks of quadriceps strength training in healthy subjects (13–15). The role of SCs in atrophy of human skeletal muscle, however, has scarcely been investigated. In the very few studies on the role of SCs in atrophy of human skeletal muscle (8, 10, 16), loss of SCs with atrophy is not a consistent finding. However, there is some evidence that a particularly severe atrophic environment, as is found, for example, after severe burn injury, has a negative impact on SC number and SC function and can induce SC apoptosis (17). With regard to findings in animal studies, it has been hypothesized that muscle wasting in old age (sarcopaenia) could at least partly be explained by SC dysfunction with increased SC apoptosis due to chronic low-grade systemic inflammation (18). The significantly reduced SC number in biopsies from the vastus lateralis muscle after ACL injury (8, 10) and the lack of increase in SC number after resumption of muscular training after ACL-R (3, 10) suggest that ACL injury and/or ACL-R with quadriceps tendon or semitendinosus tendon autografts, respectively, might generate a severe atrophic environment with negative effects on SC number and function.The primary aim of this study was to further investigate the effects of ACL-R on SCs and to determine whether the previously described reduction in SC number might be due to SC apoptosis. The study analysed muscle biopsies from the vastus lateralis muscle of recreational athletes immediately before ACL surgery and again after 12 weeks of early rehabilitation.     

Synthesis of 3-selanylbenzo[b]furans promoted by SelectFluor®

A simple and practical protocol for the synthesis of 3-selanyl-benzo[b]furans mediated by the SelectFluor® reagent was developed. This novel methodology provided a greener alternative to generate 3-substituted-benzo[b]furans via a metal-free procedure under mild conditions. The intramolecular cyclization reaction was carried out employing an electrophilic selenium species generated in situ through the reaction between SelectFluor® and organic diselenides. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy, and its reactivity was explored.

This novel methodology provided a greener alternative to generate 3-substituted-benzo[b]furans mediate by Selectfluor® reagent. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy.

The benzo[b]furan scaffold is an important structural motif that is present in natural products and in synthetic compounds with therapeutic proprieties.¹ Substituted benzo[b]furans have shown a broad range of biological activities,² being found in a variety of pharmaceutical targets, such as Viibryd® and Ancoron® (Fig. 1).³ These drugs are used for treatment of depression and for cardiac arrhythmias, respectively. An efficient method to obtain substituted benzo[b]furans is the intramolecular cyclization reaction between 2-alkynylphenol or 2-alkynylanisole derivatives with different electrophilic species to generate a wide variety of 3-substituted-benzo[b]furans. This strategy is especially useful because of the atom-economic synthesis under mild conditions.⁴Open in a separate windowFig. 1Substituted benzo[b]furans in commercial drugs.Organoselenium compounds have attracted great interest due the large number of biological applications and their versatile reactivity.⁵ From a synthetic point of view, the ease cleavage of the Se–Se bond in diselenide compounds can generate species with different reactivity, as radical, electrophile, and nucleophile. This ample usefulness becomes the diselenides in key synthetic intermediates to introduce selenium moiety in organic compounds or to catalyse organic transformations.^5,6Despite the recent advances in the synthesis of 3-selanyl-benzo[b]furans, new electrophiles and reactional conditions were explored (Scheme 1).^{7–9,11–15} Initially, the establishing work by Larock and co-workers toward the synthesis of 3-selanyl-benzo[b]furans through the intramolecular cyclization of 2-(phenylethynyl)anisole with PhSeCl in CH₂Cl₂ at room temperature.⁷ In 2009, Zeni and co-workers demonstrated the synthesis of 3-selanyl-benzo[b]furans employing PhSeBr as an active electrophile.⁸ A pioneering protocol was reported by Zeni and co-workers, which employed FeCl₃ (1.0 equiv.) and diorganyl diselenides in CH₂Cl₂ at 45 °C.⁹ Additionally, Lewis acids have been used as effective catalysts in Se–Se bonding cleavage to access functionalized selenium compounds.¹⁰ Afterward, alternative methods were developed, such as the synthesis of 3-selanyl-benzo[b]furans mediated by PdCl₂/I₂, I₂/water, and CuI (1.5 equiv.).^11–14 More recently, Liu and co-workers reported a radical cyclization reaction using selenium powder as selenium source and AgNO₃ as catalyst in DMSO at 100 °C.¹⁵Open in a separate windowScheme 1Methodologies to prepare 3-selanyl-benzo[b]furans.Although, there are different methodologies to prepare 3-selanyl-benzo[b]furans and other functionalized selenium compounds through the reaction between diselenides compounds with oxidant reagents or Lewis acids, alternative electrophilic selenium species should be employed to avoid metals and/or toxic reagents.^9–15 Furthermore, RSeCl and RSeBr,^7,8 obtained from the reaction of diselenides with SO₂Cl₂ (or Cl₂) and Br₂ respectively, are commercially available and largely used as selenylating agent. However, these species present a low stability under moisture, and the high nucleophilicity of chloride and bromide leaving groups can lead to undesirable side reactions.On the other hand, SelectFluor® is a versatile reagent used for different applications, such as fluorination reactions,¹⁶ C–H functionalization¹⁷ and organic function transfer.¹⁸ In addition, SelectFluor® has been used as an efficient method for intramolecular annulation reactions, due its higher reactivity.¹⁹ This ample application together with the desirable characteristics of the SelectFluor®, such as the higher stability, non-hydroscopic solid and hazard-free source of fluorine,²⁰ promoted new possibilities to investigate fluorine chemistry. In 2004, Poleschner and Seppelt prepared PhSeF derivatives by the reaction between diorganyl diselenides and XeF₂ in CH₂Cl₂ as a solvent at −40 °C.²¹ The products were characterized by low-temperature ¹⁹F and ⁷⁷Se NMR, and it was the first confirmation of this type of electrophilic selenium compound. Although electrophilic selenium catalysis (ESC) with electrophilic fluoride reagents as oxidants has been demonstrated in the functionalization of alkenes,²² fewer knowledge about the reactivity of this selenium electrophilic species is available in the literature.²³Based on the development of new electrophilic selenium reagents,^9–14,24 herein, we describe a metal-free synthesis of 3-selanyl-benzo[b]furans under mild conditions using this very reactive electrophilic selenium species (RSe-F), generated in situ at room temperature by the reaction of diorganyl diselenides with SelectFluor® reagent (Scheme 1). Moreover, the higher reactivity of RSe-F species could be explored for the insertion of selenium moiety in other building blocks because the environmentally friendly reactional condition, and the replacing chlorine and bromine by the non-nucleophilic fluorine counter ion, can partially circumvented some side reactions.     

Organocatalytic sulfa-Michael/aldol cascade: constructing functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter

A practical sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylates has been developed, which allows efficient access to functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter in moderate to good yields with high enantioselectivities.

A sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylate has been developed, which allows access to 2,5-dihydrothiophenes bearing a quaternary carbon center in moderate to good yields with high enantioselectivities.

Among the various classes of heterocycles, members of the thiophene family have received particular attention from the chemical community because of their widespread occurrence as ubiquitous motifs in natural products, pharmaceuticals, agrochemicals as well as materials.¹ In this context, the 2,5-dihydrothiophene ring is a common structural feature of many bioactive compounds and a potential intermediate for various synthetic applications.² Over the decades, only a few examples of the assembly of optically active 2,5-dihydrothiophenes have been documented.³ For instance, the Spino^3b group successfully prepared non-racemic dihydrothiophenes using an efficient chiral auxiliary. The first gold-catalyzed cycloisomerization of α-hydroxyallenes to 2,5-dihydrothiophenes was reported by Krause^3c and co-workers. Then in 2010, the Xu^3e group developed a highly stereoselective domino thia-Michael/aldol reaction between 1,4-dithiane-2,5-diol and α,β-unsaturated aldehyde catalyzed by a chiral diphenylprolino TMS ether, which provided a new avenue for the synthesis of functionalized 2,5-dihydrothiophenes.Quaternary carbon stereocenters are often contained in natural products and pharmaceuticals.⁴ Compared with the chiral pool synthesis,⁵ the procedure of chiral materials or catalysts to construct such sterically congested stereogenic centers is more challenging because of the difficulty of orbital overlap.⁶ To date, a lot of progresses have been made in the construction of chiral quaternary carbon centers in cyclic compounds,⁷ which are greatly accelerated by the advancement of transition metal catalysis,⁸ and organocatalysis,⁹ including methods beyond radical initiation.¹⁰ However, only few examples are about the construction of a quaternary carbon in 2,5-dihydrothiophene ring.¹¹ Inspired by the previous work of the Xu group,^3e we describe herein an elegant organocatalytic asymmetric cascade sulfa-Michael/aldol reaction, providing a convenient way for the synthesis of 2,5-dihydrothiophenes bearing a chiral quaternary cabon center.     

Water wettability of graphene: interplay between the interfacial water structure and the electronic structure

Wetting phenomena are ubiquitous and impact a wide range of applications. Simulations so far have largely relied on classical potentials. Here, we report the development of an approach that combines density-functional theory (DFT)-based calculations with classical wetting theory that allows practical but sufficiently accurate determination of the water contact angle (WCA). As a benchmark, we apply the approach to the graphene and graphite surfaces that recently received considerable attention. The results agree with and elucidate the experimental data. For metal-supported graphene where electronic interactions play a major role, we demonstrate that doping of graphene by the metal substrate significantly alters the wettability. In addition to theory, we report new experimental measurements of the WCA and the force of adhesion that corroborate the theoretical results. We demonstrate a correlation between the force of adhesion and WCA, and the use of the atomic force microscope (AFM) technique as an alternative measure for wettability at the nanoscale. The present work not only provides a detailed understanding of the wettability of graphene, including the role of electrons, but also sets the stage for studying the wettability alteration mechanism when sufficiently accurate force fields may not be available.

Wettability of graphene is characterized from first principles.

Wetting phenomena are ubiquitous in a variety of practical issues, including adhesion,¹ friction,² interfacial thermal conductance (Kapitza conductance),^3,4 to name just a few. Graphene has emerged as an important material for applications where water wettability plays a major role, e.g., as a lubricant,⁵ small-molecule gas sensor,^6,7 desalination membrane,^8,9 protective coating from electrochemical degradation,¹⁰ promotive coating for dropwise condensation,¹¹etc. Among these applications, to wet or not to wet is the key problem.^12,13 More recently, doping-induced tunable wettability was reported for graphene.^14,15Interactions between the wetting liquid and the solid it rests on are responsible for the wetting properties of a surface. The binding energy of individual molecules on the solid surface, obtained by quantum-mechanical calculations, has at times been used as an indicator of wettability.^14,16 A better indicator, however, is the water contact angle (WCA), an experimentally easily accessible parameter that characterizes macroscopically a surface''s wettability by water.^17,18 Large WCA, >90°, signifies hydrophobic behavior, whereas small WCA, <90°, signifies hydrophilic behavior. The past few years have witnessed increasing efforts to understand the wetting mechanism of graphitic carbon surfaces. Theoretical calculations of WCAs of graphitic carbon surfaces have so far been done primarily using classical potentials, by constructing an analytical interaction potential between water and the solid surface based on interatomic Lennard-Jones potentials^19–21 or classical molecular dynamics (CMD) simulations.^19,22–29 In those pioneering studies with the work-of-adhesion approach, one first computes the work of adhesion of a water slab on a surface and then employs the Young-Dupré equation that relates the work of adhesion to the WCA.^19,25–28 Alternatively, CMD can be sued to measures the shape of a water droplet on a surface and extract the WCA.^22–24Though these approaches have provided significant insights into wetting behavior,^19,22–28 they depend on the availability of reliable classical potentials. The construction of such potentials becomes a difficult task when many atomic species are present. For example, the interplay between ions such as Ca²⁺, Mg²⁺, SO₄²⁻, Na⁺ and Cl⁻ in saline water and calcite (CaCO₃) surfaces is responsible for the wettability alteration for oil recovery.^30,31 There are also cases, e.g., monolayers on metallic substrates, where explicit electron doping effects may play a major role, requiring electronic-structure calculations. While density functional theory (DFT) is the method of choice for predictive, atomic-scale calculations of interactions at the solid–water interface, the major difficulty lies in the limited time and length scales achievable by quantum MD (QMD) simulations.³² So far there exists only one report of QMD simulations of water nanodroplets, on graphene and hexagonal boron nitride monolayers.³³In this paper, we adopt the method based on the work of adhesion and the Young-Dupré equation, and employ an approximation that allows practical but sufficiently accurate DFT-based determination of the WCA. Benchmark calculations confirm that graphitic carbon surfaces are nonpolar and intrinsically hydrophilic, with their wettability determined by the dispersive interaction. The WCA gradually decreases with increasing number of graphene layers N, while a monolayer of adsorbed hydrocarbons is sufficient to render graphene hydrophobic, complementing similar results obtained using classical potentials.^20,21,25,34 In the presence of a metal substrate, electronic structure comes into play and electron doping of the graphene sheet by the metal substrate alters the wettability of graphene. We report new WCA and AFM (atomic force microscopy) measurements for Cu-supported monolayer and multilayer graphene that further corroborate the theoretical results. Finally, we demonstrate a correlation between the force of adhesion and WCA, and the use of the AFM technique as an alternative measure for wettability at the nanoscopic scale.