Mesoporous PbO nanoparticle-catalyzed synthesis of arylbenzodioxy xanthenedione scaffolds under solvent-free conditions in a ball mill

A protocol for the efficient synthesis of arylbenzodioxy xanthenedione scaffolds was developed via a one-pot multi-component reaction of aromatic aldehydes, 2-hydroxy-1,4-naphthoquinone, and 3,4-methylenedioxy phenol using mesoporous PbO nanoparticles (NPs) as a catalyst under ball milling conditions. The synthesis protocol offers outstanding advantages, including short reaction time (60 min), excellent yields of the products (92–97%), solvent-free conditions, use of mild and reusable PbO NPs as a catalyst, simple purification of the products by recrystallization, and finally, the use of a green process of dry ball milling.

An efficient one-pot multicomponent protocol was developed for the synthesis of arylbenzodioxy xanthenedione scaffolds using mesoporous PbO nanoparticles as reusable catalyst under solvent-free ball milling conditions.

Recently, the ball milling technique has received great attention as an environmentally benign strategy in the context of green organic synthesis.^1a The process of “ball milling” has been developed by adding mechanical grinding to the mixer or shaker mills. The ball milling generates a mechanochemical energy, which promotes the rupture and formation of the chemical bonds in organic transformations.^1b Subsequently, detailed literature^1c and books on this novel matter have been published.^2a,b Several typical examples include carbon–carbon and carbon–heteroatom bond formation,^2c organocatalytic reactions,^2d oxidation by using solid oxidants,^2e dehydrogenative coupling, asymmetric, and peptide or polymeric material synthesis, which have been reported under ball milling conditions.^2e Hence, the organic reactions using ball milling activation carried out under neat reaction environments, exhibit major advantages,^2f including short reaction time, lower energy consumption, quantitatively high yields and superior safety with the prospective for more improvement than the additional solvent-free conditions and clear-cut work-up.^3–5On the other hand, the organic transformations using metal and metal oxide nanoparticles⁶ are attracting enormous interest due to the unique and interesting properties of the NPs.^7,8,9a Particularly, PbO NPs^9b provide higher selectivity in some organic reactions^9c and find applications in various organic reactions, like Paal–Knorr reaction,¹⁰ synthesis of diethyl carbonate,¹¹ phthalazinediones,¹² disproportionation of methyl phenyl carbonate to synthesize diphenyl carbonate,¹³ the capping agent in organic synthesis, and selective conversion of methanol to propylene.¹⁴ In addition, the PbO NPs are also used in many industrial materials.^15,16However, till date, PbO NPs have not been explored in MCRs leading to biologically important scaffolds. Among others, the xanthene scaffolds¹⁷ are one of the important heterocyclic compounds¹⁸ and are extensively used as dyes, fluorescent ingredients for visual imaging of the bio-molecules, and in optical device technology because of their valuable chemical properties.¹⁹ The xanthene molecules have conjointly been expressed for their antibacterial activity,²⁰ photodynamic medical care, anti-inflammatory drug impact, and antiviral activity. Because of their various applications, the synthesis of these compounds has received a great deal of attention.²¹ Similarly, vitamin K nucleus^22,23 shows a broad spectrum of biological properties, like anti-inflammatory, antiviral, antiproliferative, antifungal, antibiotic, and antipyretic.^24a As a consequence, a variety of strategies^24b have been demonstrated in the literature for the synthesis of xanthenes and their keto derivatives, like rhodomyrtosone-B,^25a rhodomyrtosone-I,^25b and BF-6 ^25c as well as their connected bioactive moieties. Few biologically active xanthene scaffolds are shown in (Fig. 1).Open in a separate windowFig. 1Some biologically important xanthenes and their keto derivatives.Due to the significance of these compounds, the synthesis of xanthenes and their keto derivatives using green protocols is highly desirable. Reported studies reveal that these scaffolds are synthesized by three-component condensations using p-TSA²⁶ and scolecite²⁷ as catalysts. However, these methods suffer from the use of toxic acidic catalysts like p-TSA, long reaction times (3 h), harsh refluxing²⁶ or microwave reaction conditions,²⁷ and tedious work-up procedures. The previously reported methods for the synthesis of xanthenediones are shown in Scheme 1.Open in a separate windowScheme 1Previous protocol for the synthesis of xanthenedione derivatives.Herein, we report an economical and facile multicomponent protocol, using ball milling, for the synthesis of 7-aryl-6H-benzo[H][1,3]dioxolo[4,5-b]xanthene-5,6(7H)-dione using PbO NPs as a heterogeneous catalyst (Scheme 2). The PbO NPs are non-corrosive, inexpensive, and easily accessible.Open in a separate windowScheme 2General reaction scheme of PbO NP-catalyzed synthesis of the xanthenedione scaffolds under ball milling conditions.In our protocol,²⁸ the PbO NPs were initially prepared by mixing sodium dodecyl sulphate (2.5 mmol) and sodium hydroxide (10 mL, 0.1 N) with an aqueous methanolic solution of lead nitrate (2 mmol) under magnetic stirring at 30 °C by continuing the reaction for 2 h. Then, the obtained white polycrystalline product was filtered, washed with H₂O, and dried at 120 °C, followed by calcination at 650 °C for 2 h. During this step, the white PbO NPs turned pale yellow in colour. Eventually, the synthesized PbO was then characterized by spectroscopic and analytical techniques.The powder X-ray diffraction (XRD) pattern revealed the crystalline nature of the PbO NPs as the diffraction peaks corresponding to (131), (311), (222), (022), (210), (200), (002), and (111) crystal planes were identified (Fig. 2). The XRD outline of the synthesized PbO NPs was further established for the formation of space group Pca2₁ ²⁹ with a single orthorhombic structure (JCPDS card number 76-1796). The sharp diffraction peaks indicated good crystallinity, and the average particle size of the PbO NPs was estimated to be 69 nm, as calculated using the Debye–Scherer equation.Open in a separate windowFig. 2The powder XRD pattern of PbO NPs.The surface morphology of the PbO NPs was analyzed by scanning electron microscopy (SEM), and the SEM image revealed the discrete and spongy appearance of the PbO NPs (Fig. 3).Open in a separate windowFig. 3The SEM image of PbO NPs.Moreover, the elemental composition obtained from energy dispersive X-ray (EDX) analysis confirmed that the material contains Pb and O elements, and no other impurity was present (Fig. 4).Open in a separate windowFig. 4The EDAX spectrum of crystalline PbO NPs.The transmission electron microscopy (TEM) image shown in Fig. 5 indicated the formation of orthorhombic crystallites of PbO with several hexagon-shaped particles. The dark spot in the TEM micrograph further confirmed the synthesis of PbO NPs, as the selected area diffraction pattern associated with such spots reveals the occurrence of the PbO NPs in total agreement with the X-ray diffraction data (Fig. 6). The average size of the PbO nanocrystals by TEM was approximated to be around 20 nm.Open in a separate windowFig. 5The TEM image of nanocrystalline PbO NPs.Open in a separate windowFig. 6The SAED image of nanocrystalline PbO NPs.The Fourier transform infrared (FT-IR) spectrum (ESI, S6^†) of the PbO NPs displayed peaks at 575, 641, and 848 cm⁻¹, which corresponds to the Pb–O vibrations. Furthermore, the absorption band at ∼3315 cm⁻¹ was due to the presence of the hydroxyl group (–OH) in the NPs.The N₂ adsorption–desorption isotherms of the PbO nanoparticles shown in Fig. 7 was consistent with type IV adsorption–desorption isotherms with H1 hysteresis corresponding to the cylindrical mesoporous structure. Moreover, the surface area, pore-volume, and BJH pore diameter were found to be 32.0 m² g⁻¹, 0.023 cm³ g⁻¹, and 30.9 Å, respectively.Open in a separate windowFig. 7BET surface area and pore size of nanocrystalline PbO catalyst.The catalytic activity of the synthesized PbO NPs was tested in a one-pot multicomponent synthesis of arylbenzodioxoloyl xanthenedione derivative under ball milling condition according to the reaction scheme 2a, with 3,4-dimethoxybenzaldehyde (166.2 mg, 1.0 mmol), 3,4-methylenedioxyphenol (138.0 mg, 1.0 mmol), and 2-hydroxy-1,4-naphthoquinone (174.0 mg, 1.0 mmol) as reactants. The reaction conditions, the ball milling parameters (speed, time, and ball to solids ratio), and the PbO nanocatalyst amount were first optimized to produce the highest yield using experimental design as shown in

Self-assembled pearl-necklace patterned upconverting nanocrystals with highly efficient blue and ultraviolet emission: femtosecond laser based upconversion properties

This work reports new findings on the formation of a pearl-necklace pattern in self-assembled upconverting nanocrystals (UCN-PNs) which exhibit strong upconversion emission under an NIR excitation source of a femtosecond laser (Fs-laser). Each nano-necklace consists of several upconversion nanoparticles (UCNPs) having a size ca. 10 ± 1 nm. UCN-PNs are arranged in a self-organized manner to form necklace type chains with an average length of 140 nm of a single row of nanoparticles. Furthermore, UCN-PNs are comprised of UCNPs with an average interparticle separation of ca. 4 nm in each of the nanonecklace chains. Interestingly, these UCN-PNs exhibit high energy upconversion especially in the UV region on interaction with a 140 Fs-laser pulse duration at 80 MHz repetition rate and intense blue emission at 450 nm on interaction with a 900 nm excitation source is obtained. The preparation of self-assembled UCNPs is easy and they are very stable for a longer period of time. The emission (fluorescence/luminescence) intensity is very high which can make them unique in innumerable industrial and bio-applications such as for disease diagnosis and therapeutic applications by targeting the infected cells with enhanced efficiency.

Self-assembled pearl necklace patterned-upconverting nanoparticles and their femtosecond laser based upconversion properties.     

Cross-match-compatible platelets improve corrected count increments in patients who are refractory to randomly selected platelets

Background

Cross-match-compatible platelets are used for the management of thrombocytopenic patients who are refractory to transfusions of randomly selected platelets. Data supporting the effectiveness of platelets that are compatible according to cross-matching with a modified antigen capture enzyme-linked immunosorbent assay (MAC-ELISA or MACE) are limited. This study aimed to determine the effectiveness of cross-match-compatible platelets in an unselected group of refractory patients.

Materials and methods

One hundred ABO compatible single donor platelet transfusions given to 31 refractory patients were studied. Patients were defined to be refractory if their 24-hour corrected count increment (CCI) was <5×10⁹/L following two consecutive platelet transfusions. Platelets were cross-matched by MACE and the CCI was determined to monitor the effectiveness of platelet transfusions.

Results

The clinical sensitivity, specificity, positive predictive value and negative predictive value of the MACE-cross-matched platelets for post-transfusion CCI were 88%, 54.6%, 39.3% and 93.2%, respectively. The difference between adequate and inadequate post-transfusion 24-hour CCI for MACE cross-matched-compatible vs incompatible single donor platelet transfusions was statistically significant (p=0.000). The 24-hour CCI (mean±SD) was significantly higher for cross-match-compatible platelets (9,250±026.6) than for incompatible ones (6,757.94±2,656.5) (p<0.0001). Most of the incompatible cross-matches (73.2%) were due to anti-HLA antibodies, alone (55.3% of cases) or together with anti-platelet glycoprotein antibodies (17.9%).

Discussion

The clinical sensitivity and negative predictive value of platelet cross-matching by MACE were high in this study and such tests may, therefore, be used to select compatible platelets for refractory patients. A high negative predictive value demonstrates the greater chance of an adequate response with cross-matched-compatible platelets.     

Effect of sex steroids on soleus muscle response in hypocalcemic medium (in vitro)

Purpose

Postoperative hypocalcemia is a frequently encountered complication of thyroid surgery. Since hypocalcemic symptoms are closely associated with sex, the aim of this study is to investigate the effects of sex steroids on muscle tissue under hypocalcemic conditions.

Methods

Six groups consisting of control male (M), control female (F), gonadectomized male (M−), gonadectomized female (F−), estradiol-applied gonadectomized male (MX), and testosterone-applied gonadectomized female (FX) rats were used. Contraction recordings were obtained from soleus muscle flaps. Maximal tension (PT), frequency required for 50% of PT (F50), contraction velocity at F50 (V50), and changes in contraction values (d[PT], d[F50], d[V50]) between normocalcemic and hypocalcemic conditions were calculated.

Results

d[PT], d[F50], and d[V50] were significantly higher in M− and MX groups compared with control M group. Whereas d[PT], d[F50], and d[V50] parameters of the F− group were significantly higher than control F group, d[F50] and d[PT] of the FX group showed no significant change and d[V50] for the FX group was significantly lower. A comparison of control groups showed that d[PT], d[F50], and d[V50] of the F group were significantly higher than those of the M group.

Conclusion

Whereas absence of both testosterone and estradiol caused an increase in hypocalcemia-induced changes in contraction parameters of rat skeletal muscle, presence or application of testosterone clearly stabilized contraction parameters.     

One-step dry synthesis of an iron based nano-biocomposite for controlled release of drugs

Bio-based drug carriers have gained significant importance in Control Drug Delivery Systems (CDDS). In the present work, a new iron-based magnetic nano bio-composite (nano-Fe-CNB) is developed in a one-step dry calcination process (solventless) using a seaweed-based biopolymer. The detailed analysis of the developed nano Fe-CNB is carried out using FE-SEM, HR-TEM, P-XRD, XPS, Raman spectroscopy, FTIR etc. and shows that nano-Fe-CNB consists of nanoparticles of 5–10 nm decorated on 7–8 nm thick 2-D graphitic carbon material. The impregnation of nano-Fe-CNB into the calcium alginate (CA) hydrogel beads is found to have good drug loading capacity as well as pH responsive control release behavior which is demonstrated using doxorubicin (DOX) as a model cancer drug. The drug loading experiments exhibit ∼94% loading of DOX and release shows ∼38% and ∼8% release of DOX at pH 5.4 and 7.4 respectively. The developed nano Fe-CNB facilitates strong electrostatic interactions with cationic DOX molecules at pH 7.4 and thereby restricts the release of the drug at physiological pH. However, at cancer cell pH (5.4), the interaction between the drug and nano-Fe-CNB reduces which facilitates more drug release at pH 5.4. Thus, the developed nano-biocomposite has the potential to reduce the undesired side effects associated with faster release of drugs.

Schematics for synthesis and application of magnetic nano-biocomposite for control release of DOX.     

A prospective, randomized, double-blind study to compare the efficacy of lidocaine + metoclopramide and lidocaine + ketamine combinations in preventing pain on propofol injection

Purpose

Propofol injection is known to cause distressing pain, and various methods have been used to decrease this pain. We investigated the efficacy of the lidocaine + metoclopramide and lidocaine + ketamine combinations on modulating propofol injection pain.

Methods

Ninety ASA I/II patients aged 20–60 years were randomly assigned to three groups to receive lidocaine 20 mg (group L), lidocaine 20 mg + metoclopramide 10 mg (group LM), or lidocaine 20 mg + ketamine 5 mg (group LK), respectively, with venous occlusion for 1 min using a forearm tourniquet. Propofol 0.5 mg/kg was subsequently administered into a dorsal hand vein, and pain was assessed during its injection using a verbal rating score. The results were analyzed statistically with analysis of variance, the chi-square test, and the Wilcoxon rank sum test, where appropriate. The significance level was set at p < 0.05.

Results

The incidence of pain was rated to be significantly less in patients in groups LM (40 %) and LK (6.7 %) than in those in group L (83.3 %) (p = 0.001 and p < 0.001, respectively). The pain score [median (range)] was also significantly less in patients in groups LM [0 (0–3)] and LK [0 (0–2)] than in those in group L [2 (0–3)] (p = 0.001 for both groups).

Conclusion

The lidocaine–ketamine combination is most effective for decreasing the pain on propofol injection.     

The effect of acrylamide incorporation on the thermal and physical properties of denture resins

PURPOSE

Polymethyl methacrylate (PMMA) is the most commonly used denture base material despite typically low in strength. The purpose of this study was to improve the physical properties of the PMMA based denture base resins (QC-20, Dentsply Ltd., Addlestone, UK; Stellon, AD International Ltd, Dentsply, Switzerland; Acron MC; GC Lab Technologies Inc., Alsip, Japan) by copolymerization mechanism.

MATERIALS AND METHODS

Control group specimens were prepared according to the manufacturer recommendations. In the copolymer groups; resins were prepared with 5%, 10%, 15% and 20% acrylamide (AAm) (Merck, Hohenbrunn, Germany) content according to the moleculer weight ratio, respectively. Chemical structure was characterized by a Bruker Vertex-70 Fourier transform infrared spectroscopy (FTIR) (Bruker Optics Inc., Ettlingen, Germany). Hardness was determined using an universal hardness tester (Struers Duramin, Struers A/S, Ballerup, Denmark) equipped with a Vickers diamond penetrator. The glass transition temperature (T_g) of control and copolymers were evaluated by Perkin Elmer Diamond DSC (Perkin Elmer, Massachusetts,USA). Statistical analyses were carried out using the statistical package SPSS for Windows, version 15.0 (SPSS, Chicago, IL, USA). The results were tested regarding the normality of distribution with the Shapiro Wilk test. Data were analyzed using ANOVA with post-hoc Tukey test (P<.01).

RESULTS

The copolymer synthesis was confirmed by FTIR spectroscopy. Glass transition temperature of the copolymer groups were higher than the control groups of the resins. The 10%, 15% and 20% copolymer groups of Stellon presented significantly higher than the control group in terms of hardness. 15% and 20% copolymer groups of Acron MC showed significantly higher hardness values when compared to the control group of the resin. Acrylamide addition did not affect the hardness of the QC-20 resin significantly.

CONCLUSION

Within the limitation of this study, it can be concluded that copolymerization of PMMA with AAm increased the hardness value and glass transition temperature of PMMA denture base resins.     

Psychiatric disorders and characteristics of abuse in sexually abused children and adolescents with and without intellectual disabilities

The purpose of this study was to compare sexually abused children and adolescents, with and without intellectual disabilities (ID), in terms of post-abuse psychiatric disorders, features of the sexual abuse, and sociodemographic characteristics. The study included sexually abused children aged 6–16 years, who were sent to three different child mental health units for forensic evaluation; there were 102 cases (69 girls and 33 boys) with ID and 154 cases (126 girls and 28 boys) without ID. Researchers retrospectively examined the files, social examination reports, and the judicial reports of the cases. It was determined that in the group with ID, sexual abuse types including penetration and contact had higher rates, they were exposed to more frequent repeated abuses, the abuses were revealed with their own reports at a later period and lower rates, and post-abuse pregnancies were more frequent. It was also determined that the abuser was a familiar person and a family member at lower rates and more than one abuser was encountered more frequently, compared to the group without ID. While no difference was determined between the two groups in terms of the frequency of post-abuse post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), conduct disorder (CD) was observed more frequently in the group with ID. This study emphasizes that sexual abuse, which is an important problem in individuals with ID, has different features and effects.     

Gender and Racial Disparity among Addiction Psychiatry Fellows in the United States

Psychiatric Quarterly - The United States (US) has a culturally diverse population. However, the percentage of underrepresented minorities (URMs) and women in healthcare does not fully reflect...