Dynamic porous organic polymers with tuneable crosslinking degree and porosity

Porous organic polymers (POPs) show enormous potential for applications in separation, organic electronics, and biomedicine due to the combination of high porosity, high stability, and ease of functionalisation. However, POPs are usually insoluble and amorphous materials making it very challenging to obtain structural information. Additionally, important parameters such as the exact molecular structure or the crosslinking degree are largely unknown, despite their importance for the final properties of the system. In this work, we introduced the reversible multi-fold nitroxide exchange reaction to the synthesis of POPs to tune and at the same time follow the crosslinking degree in porous polymer materials. We synthesised three different POPs based on the combination of linear, trigonal, and tetrahedral alkoxyamines with a tetrahedral nitroxide. We could show that modulating the equilibrium in the nitroxide exchange reaction, by adding or removing one nitroxide species, leads to changes in the crosslinking degree. Being able to modulate the crosslinking degree in POPs allowed us to investigate both the influence of the crosslinking degree and the structure of the molecular components on the porosity. The crosslinking degree of the frameworks was characterised using EPR spectroscopy and the porosity was determined using argon gas adsorption measurements. To guide the design of POPs for desired applications, our study reveals that multiple factors need to be considered such as the structure of the molecular building blocks, the synthetic conditions, and the crosslinking degree.

We synthesised three different POPs via a nitroxide exchange reaction and modulated their crosslinking degree. That allowed us to investigate the influence of the crosslinking degree and the structure of the molecular components on the porosity.

Various approaches to synthesise porous organic polymers (POPs)^1–3 and conjugated microporous polymers (CMPs)^4,5 have been developed to form extremely stable but at the same time highly porous solids based on simple organic building blocks.^6,7 The organic nature allows for functionalisation of the materials using organic chemistry, while the high porosity makes the active components accessible throughout the entire material.⁸ The combination of high porosity, high stability, and ease of functionalisation results in the enormous potential of POPs for applications in separation, organic electronics, and biomedicine.^2,9–14 However, unlike the related covalent organic frameworks (COFs),^15–20 metal–organic frameworks (MOFs)^21,22 or porous coordination polymers (PCPs),²³ the synthesis of POPs and CMPs is based on irreversible reactions, which leads to insoluble and amorphous materials and makes it very challenging to obtain structural information. Additionally, important parameters such as the exact molecular structure or the crosslinking degree are largely unknown, despite their unarguably large influence on the final properties of the system.^24,25To investigate the molecular structure of the organic linkers between the centres of two similar CMP materials, the group of Bunz and co-workers introduced molecular building blocks that were modified with digestible groups or cores, by substituting carbon with tin as the central atom.²⁴ This tin centre can be digested, resulting in molecular fragments of the frameworks, which were analysed using nuclear magnetic resonance (NMR) spectroscopy. The obtained fragments show a surprisingly varied chemical composition of these networks.²⁴ In a previous study, we could show that the introduction of digestible germanium nodes in one of the building blocks of POPs can also be used for partial disruption of the framework and therefore causing a decrease or allow tuning of the porosity.²⁵ In another approach, we introduced a poly(disulfide) hyper-crosslinked polymer, which can be surface modified using unreacted thiol functions on the surface of the material.²⁶ Digestion of the samples helped to quantify the functionalisation. Employing digestible crosslinker or nodes is an attractive approach to gain insight into the structure or functionalisation of the frameworks. However, it requires the destruction of the sample and does not allow to modulate or tune the crosslinking degree reversibly in one particular system.In order to tune and at the same time follow the crosslinking degree in porous polymer materials, we introduce the reversible multi-fold nitroxide exchange reaction to the synthesis of POPs. The nitroxide exchange reaction has been used in material science for self-assembly of polymer materials²⁷ or micron-sized crystals,²⁸ for surface functionalisation,²⁹ or introducing self-healing properties to materials.³⁰ In addition, the combination of light-sensitive alkoxyamines was employed in surface coating³¹ or the creation of systems out of their equilibrium.³² The radical nature of the involved nitroxide species allows to follow the progress of the reaction and to directly determine the crosslinking degree of the final material using fluorescence spectroscopy^33,34 and electron paramagnetic resonance (EPR) spectroscopy.^35,36 The dynamic nature of the nitroxide exchange reaction allowed us to tune the crosslinking degree of the materials by varying the ratio of the two nitroxide species involved in the reaction and thereby modulating the equilibrium conditions (see Fig. 1).Open in a separate windowFig. 1Dynamic equilibrium in the nitroxide exchange reaction using two different nitroxide species, TEMPO (red) and isoindoline (green). The free nitroxide radical species are electron paramagnetic resonance (EPR) active, while the bound species are EPR silent.Next to the crosslinking degree, also the structure, rigidity, and the intrinsic free volume of the molecular components of POPs or CMPs play an important role to obtain porosity in the final material.⁶ Cooper and co-workers showed the importance of monomer design for the pore size and surface area of CMPs by systematically varying the strut length in a series of molecular building blocks.³⁷In order to study the influence of both the molecular structure and the crosslinking degree on the porosity of the final material, we produced three different POPs based on the combination of linear, trigonal, and tetrahedral alkoxyamines with tetrahedral nitroxides. We characterised the frameworks using EPR spectroscopy and argon gas adsorption measurements to determine the crosslinking degree and porosity. Furthermore, we could show that modulating the equilibrium in the nitroxide exchange reaction, by adding or removing one nitroxide species, leads to changes in the crosslinking degree and investigated this influence on the porosity of the frameworks.     

Use of Private Sector Workforce Respiratory Disease Short-Term Disability Claims to Assess SARS-CoV-2, Mexico, 2020

We examined respiratory disease short-term disability claims submitted to the Mexican Social Security Institute during 2020. A total of 1,631,587 claims were submitted by 19.1 million insured workers. Cumulative incidence (8.5%) was 3.6 times higher than that for January 2015‒December-2019. Workers in healthcare, social assistance, self-service, and retail stores were disproportionately affected.     

Ramadan Nutritional Strategy: Professional Soccer Player Case Study

The period of Ramadan induces changes in the usual eating patterns of individuals. During this period, Muslims must abstain from drinking and eating from dawn to dusk. Therefore, some research conducted on professional soccer players has observed that during and/or after Ramadan, performance, running speed, agility, dribbling speed, and endurance and/or skill performance in athletic events may be negatively affected by Ramadan intermittent fasting (RIF). The objective of this study was to analyze the influence of a dietary plan during RIF on performance and body composition in a professional soccer player. A 20-year-old elite player (86.0 kg, 188.5 cm) followed a dietary-nutritional plan with an isocaloric diet and was supplemented with glycerol. The athlete’s strength and power in the lower limbs was assessed by performing a countermovement jump (CMJ) and Abalakov vertical jump (ABK) before and after Ramadan. After nutritional planning, the patient’s body composition improved in terms of fat loss (6.61 to 5.70%) and muscle mass gain (50.26 to 51.50%). In addition, this translated into improvements in performance tests, both in the CMJ (36.72 to 40.00 cm) and ABK (39.16 to 49.34 cm). In conclusion, during a period of fasting, personalised nutritional planning and an appropriate supplementation and rest protocol can improve the body composition and performance of soccer players.     

Colonic Microbiota Profile Characterization of the Responsiveness to Dietary Fibre Treatment in Hypercholesterolemia

This study aimed to determine how the microbiota profile might be predisposed to a better response in blood lipid profiles due to dietary fibre supplementation. A three-arm intervention study that included three different fibre types (mainly insoluble, soluble, and antioxidant fibre) supplemented (19.2 g/day) during 2 months in individuals with hypercholesterolemia was developed. Changes in faecal microbiota and blood lipid profile after fibre supplementation were determined. In all volunteers, regardless of fibre type, an increase in the abundance of Bifidobacterium was observed, and similarly, an inverse relationship between faecal propionic acid and blood LDL-cholesterol, LDL particle size, and LDL/HDL particle ratio (p-values 0.0067, 0.0002, and 0.0067, respectively) was observed. However, not all volunteers presented an improvement in lipid profile. The non-responders to fibre treatment showed a decrease in microbiota diversity (Shannon and Simpson diversity index p-values of 0.0110 and 0.0255, respectively) after the intervention; where the reduction in short-chain fatty acids (SCFAs) producing bacterial genera such as Clostridium XIVa and Ruminococcus after dietary fibre treatment was the main difference. It was concluded that the non-responsiveness to dietary fibre treatment might be mediated by the lack of ability to maintain a stable SCFA producing bacteria diversity and composition after extra fibre intake.     

Role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in Peyronie's disease:a new diagnostic approach to predict the stage of the disease?

Neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)have been associated with multiple entities and several types of cancers.They can be ass...     

Protective and Risk Factors for Humerus Head Necrosis After Proximal Humerus Fracture Treated with Internal Locking Plate

BackgroundProximal humerus fractures (PHF) are common and lead to post-traumatic humerus head necrosis (HHN) in 3–35% after ORIF with an internal locking plate. Few studies focus on this condition and risk factors remain a discussion topic. Hertel’s criteria for initial head ischemia right after fracture (fracture complexity, medial hinge displacement and short metaphyseal head extension) have recently been correlated to HHN, but there is still a clear lack of evidence on the topic. Due to its anatomical similarities to the proximal femur, some authors argue that PHF may as well benefit from early surgery to avoid head necrosis.MethodsIn this 10-year retrospective study, we assessed 305 patients from a single center. All cases were treated with a PHILOS plate through a deltopectoral approach. The mean follow-up time was 467 days. The primary endpoint was HHN.ResultsHHN was diagnosed in 12 patients (4%), 10 of which were diagnosed within the first year and one case 4 years after surgery. A positive correlation (p < 0.04) was found between HHN and fracture type (both in AO and Neer’s classification), initial neck-shaft-angle (NSA) and metaphyseal head extension (MHE). Medial hinge displacement (MHD) occurred in all HHN cases. Achieving perfect reduction (< 2 mm dislocation) was relevant to avoiding HHN (p = 0.035). Although HHN developed in 32% of the high risk cases (four-part fractures with a short MHE), it was completely avoided (0%) when perfect reduction was achieved. Time until surgery after admission was neither a protective nor a risk factor for HHN.ConclusionWe conclude that fracture complexity (four-part and C-fractures) as well as disruption of the medial hinge with a metaphyseal head extension smaller than 8 mm are relevant risk factors for humerus head necrosis. A combination of these criteria generated an high risk pattern with a 32% rate of HHN. Though often difficult to achieve, perfect reduction was a clear protective factor and reduced HHN to 0%. Perfect reduction may be key to inosculation and, therefore, salvage of the humerus head, especially in high risk cases. Surgery timing did not correlate with HHN.Level of EvidenceLevel 3, retrospective cohort study.     

Social Cognition in Chiari Malformation Type I: a Preliminary Characterization

Chiari malformation type I (CM-I) is a neurological disorder in which cerebellar tonsils are herniated through the foramen magnum into the spinal canal. A     

Combined use of cytology,p16 immunostaining and genotyping for triage of women positive for high-risk human papillomavirus at primary screening

Human papillomavirus (HPV) testing is very sensitive for primary cervical screening but has low specificity. Triage tests that improve specificity but maintain high sensitivity are needed. Women enrolled in the experimental arm of Phase 2 of the New Technologies for Cervical Cancer randomized controlled cervical screening trial were tested for high-risk HPV (hrHPV) and referred to colposcopy if positive. hrHPV-positive women also had HPV genotyping (by polymerase chain reaction with GP5+/GP6+ primers and reverse line blotting), immunostaining for p16 overexpression and cytology. We computed sensitivity, specificity and positive predictive value (PPV) for different combinations of tests and determined potential hierarchical ordering of triage tests. A number of 1,091 HPV-positive women had valid tests for cytology, p16 and genotyping. Ninety-two of them had cervical intraepithelial neoplasia grade 2+ (CIN2+) histology and 40 of them had CIN grade 3+ (CIN3+) histology. The PPV for CIN2+ was >10% in hrHPV-positive women with positive high-grade squamous intraepithelial lesion (61.3%), positive low-grade squamous intraepithelial lesion (LSIL+) (18.3%) and positive atypical squamous cells of undetermined significance (14.8%) cytology, p16 positive (16.7%) and, hierarchically, for infections by HPV33, 16, 35, 59, 31 and 52 (in decreasing order). Referral of women positive for either p16 or LSIL+ cytology had 97.8% sensitivity for CIN2+ and women negative for both of these had a 3-year CIN3+ risk of 0.2%. Similar results were seen for women being either p16 or HPV16/33 positive. hrHPV-positive women who were negative for p16 and cytology (LSIL threshold) had a very low CIN3+ rate in the following 3 years. Recalling them after that interval and referring those positive for either test to immediate colposcopy seem to be an efficient triage strategy. The same applies to p16 and HPV16.