Synthesis of Cu (II) and Zn (II) Complexes of a Quinoline Based Flexible Amide Receptor as Fluorescent Probe for Dihydrogen Phosphate and Hydrogen Sulphate and Their Antibacterial Activity.

A novel 8-hydroxy quinoline-derived amide receptor, in conjunction with its Cu (II) and Zn (II) complexes, has been strategically developed to function as remarkably efficient fluorescent receptors with a distinct capability for anion sensing. The comprehensive characterization of the synthesized compounds were achieved through UV-Vis, IR, NMR, and HRMS spectroscopic techniques. Among the Cu (II) and Zn (II) complexes, the latter exhibits superior selectivity for anions, specifically dihydrogen phosphate and hydrogen sulfate, as their tetrabutylammonium salts in a 9:1 acetonitrile-water (v/v) mixture. The Cu (II) complex demonstrates enhanced anion binding compared to the amide ligand, albeit with reduced selectivity. Furthermore, the affinity was evaluated using the Benesi-Hildebrand plot. The binding constants and Limit of Detection (LOD) for both complexes were precisely quantified. The Job plot illustrates a clear 1:1 binding interaction between the metal complexes and the guest anions. Significantly, both metal-complex receptors display a broad spectrum of antibacterial activity, against both gram-positive and gram-negative bacteria. It is worth highlighting that the Zn (II) complexed receptor outperforms the Cu (II) complexed receptor, as evidenced by its considerably lower Minimum Inhibitory Concentration (MIC) value against both bacterial strains.

Asymmetric Reactions of N-Phosphonyl/Phosphoryl Imines.

The asymmetric reactions of imines continued to attract the attention of the scientific community for decades. However, the stereoselective reactions of N-phosphonyl/phosphoryl imines remained less explored as compared to other N-substituted imines. The chiral auxiliary-based asymmetric-induction strategy with N-phosphonyl imines could effectively generate enantio- and diastereomeric amine, α,ß-diamine, and other products through various reactions. On the other hand, the asymmetric approach for the generation of chirality through the utilization of optically active ligands, along with metal catalysts, could be successfully implemented on N-phosphonyl/phosphoryl imines to access numerous synthetically challenging chiral amine scaffolds. The current review critically summarizes and reveals the literature precedence of more than a decade to highlight the major achievements existing to date that can display a clear picture of advancement as well drawbacks in this area.

Visiblelight-induced ternary electron donor-acceptor complex enabled synthesis of 2-(2-hydrazinyl) thiazole derivatives and the assessment of their antioxidant and antidiabetic therapeutic potential.

A mild and eco-friendly visible-light-induced synthesis of 2-(2-hydrazinyl) thiazole from readily accessible thiosemicarbazide, carbonyl, and phenacyl bromide in the absence of a metal catalyst and/or any extrinsic photosensitizer is reported. This approach only requires a source of visible light and a green solvent at room temperature to produce the medicinally privileged scaffolds of hydrazinyl-thiazole derivatives in good to outstanding yields. Experimental studies support the in situ formation of a visible-light-absorbing, photosensitized colored ternary EDA complex. The next step is to prepare a pair of radicals in an excited state, which makes it easier to prepare thiazole derivatives through a SET and PCET process. DFT calculations additionally supported the mechanistic analysis of the course of the reaction. The antioxidant and antidiabetic properties of some of the compounds in the synthesized library were tested in vitro. All the investigated compounds demonstrated appreciable antioxidant activity, as evidenced by the reducing power experiment and the IC50 values of the DPPH radical scavenging experiment. Furthermore, the IC50 values for 4c, 4d, and 4g also demonstrated a strong α-amylase inhibitory effect.

Effects of type 2 diabetes on the viscoelastic behavior of human trabecular bone.

Type 2 diabetes (T2D) is a well-known disease that impaired bone mechanical properties and increases the risk of fragility fracture. The bone tissue is a viscoelastic material that means the loading rate determines its mechanical properties. This study investigates the impact of T2D on the viscoelastic properties of human bone and its association with microstructure and biochemical properties. INTRODUCTION: Viscoelasticity is an important mechanical property of bone and for this the interaction of individual constituents of bone plays an important role. The viscoelastic nature of bone can be affected by aging and diseases, which can further influence its deformation and damage behavior. METHODS: The present study investigated the effects of T2D on the viscoelastic behavior of trabecular bone. The femoral heads of T2D (n = 26) and non-T2D (n = 40) individuals with hip fragility fractures were collected for this investigation. Following the micro-CT scanning of all bone samples, the stress relaxation and dynamic mechanical analysis (DMA) tests were performed to quantify the viscoelasticity of bone. Further, a correlation analysis was performed to investigate the effects of alteration in bone microstructural and biochemical parameters on viscoelasticity. RESULTS: The stress relaxation and frequency sweep responses of T2D and non-T2D trabecular bone specimens were not found significantly different. However, the storage modulus, initial stiffness, and initial stress were found lower in T2D bone. The significant correlation of percentage stress relaxed is obtained between the mineral content (r= - 0.52, p-value = 0.003), organic content (r = 0.40, p-value = 0.02), and mineral-to-matrix ratio (r = - 0.43, p-value = 0.009). Further, storage and loss modulus were correlated with bone volume fraction (BV/TV) for both groups. The stress relaxation and frequency sweep characteristics were not found significantly connected with the other chemical, structural, or clinical parameters. CONCLUSION: This study suggests that T2D does not affect the time-dependent response of human femoral trabecular bone. The viscoelastic properties are positively correlated with organic content and negatively correlated with mineral content.

Can fingernail quality predict bone damage in Type 2 diabetes mellitus? a pilot study.

Type 2 diabetes mellitus (T2DM) adversely affects the normal functioning, intrinsic material properties, and structural integrity of many tissues, including bone. It is well known that the clinical utility of areal bone mineral density (aBMD) is limited to assess bone strength in individuals with T2DM. Therefore, there is a need to explore new diagnostic techniques that can better assist and improve the accuracy of assessment of bone tissue quality. The present study investigated the link between bone and fingernail material/compositional properties in type 2 diabetes mellitus (T2DM). For that, femoral head and fingernail samples were obtained from twenty-five adult female patients (with/without T2DM) with fragility femoral neck fractures undergoing hemi/total hip arthroplasty. Cylindrical cores of trabecular bone were subjected to micro-CT, and lower bone volume fraction was observed in the diabetic group than the non-diabetic group due to fewer and thinner trabeculae in individuals with T2DM. The material and compositional properties of bone/fingernail were estimated using nanoindentation and Fourier Transform Infrared Spectroscopy, respectively. Both bone/fingernails in T2DM had lower reduced modulus (Er), hardness (H), lower Amide I and Amide II area ratio (protein content), higher sugar-to-matrix ratio, and relatively high carboxymethyl-lysine (CML) content compared with non-diabetic patients. Sugar-to-matrix ratio and relative CML content were strongly and positively correlated with HbA1c for both bone/fingernail. There was a positive correlation between bone and fingernail glycation content. Our findings provide evidence that the degradation pattern of bone and fingernail properties go hand-in-hand in individuals with T2DM. Hence, the fingernail compositional/material properties might serve as a non-invasive surrogate marker of bone quality in T2DM; however, further large-scale studies need to be undertaken.

Effect of ageing on microstructure and fracture behavior of cortical bone as determined by experiment and Extended Finite Element Method (XFEM).

Bone fracture is a severe health concern; therefore, understanding the causes of bone fracture are crucial. This paper investigates the microstructure and fracture behaviour of cadaveric cortical bone of two different groups (Young, n= 6; Aged, n=7). The microstructure is obtained from µ-CT images, and the material parameters are measured with nanoindentation. Fracture behaviour in transverse and longitudinal orientations is investigated experimentally and numerically. The results show that the Haversian canal (HC) size increases and the osteon wall thickness (OWT) decreases significantly in the aged group, whereas a nonsignificant difference is found in tissue properties. The crack initiation (Jic) and crack growth (Jgrow) toughness of the aged group are found to be significantly lower (p<0.01) than the young group in the transverse orientation; however, for the longitudinal orientation, only the value of Jic in the aged group is found significantly lower. Further, a 4-phase XFEM (based on micro-CT image) model is developed to investigate the crack propagation behaviour in both orientations. For the transverse orientation, results show that in the aged group, the crack initially follows the cementline and then penetrates the osteon, whereas, in the young group, it propagates along the cementline. These results are in agreement with experimental results where the decrease in Jgrow is more significant than the Jic in the aged group. This study suggests that ageing leads to a larger HC and reduced OWT, which weakens the crack deflection ability and causes fragility fracture. Further, the XFEM results indicate that the presence of a small microcrack in the vicinity of a major crack tip causes an increase in the critical stress intensity factor.

Prediction of mechanical properties of trabecular bone in patients with type 2 diabetes using damage based finite element method.

Type-2 diabetic (T2D) and osteoporosis (OP) suffered patients are more prone to fragile fracture though the nature of alteration in areal bone mineral density (aBMD) in these two cases are completely different. Therefore, it becomes crucial to compare the effect of T2D and OP on alteration in mechanical and structural properties of femoral trabecular bone. This study investigated the effect of T2D, OP, and osteopenia on bone structural and mechanical properties using micro-CT, nanoindentation and compression test. Further, a nanoscale finite element model (FEM) was developed to predict the cause of alteration in mechanical properties. Finally, a damage-based FEM was proposed to predict the pathological related alteration of bone's mechanical response. The obtained results demonstrated that the T2D group had lower volume fraction (-18.25%, p = 0.023), young's modulus (-23.47%, p = 0.124), apparent modulus (-37.15%, p = 0.02), and toughness (-40%, p = 0.001) than the osteoporosis group. The damage-based FE results were found in good agreement with the compression experiment results for all three pathological conditions. Also, nanoscale FEM results demonstrated that the elastic and failure properties of mineralised collagen fibril decreases with increase in crystal size. This study reveals that T2D patients are more prone to fragile fracture in comparison to OP and osteopenia patients. Also, the proposed damage-based FEM can help to predict the risk of fragility fracture for different pathological conditions.

Investigation of Mechanical, Material, and Compositional Determinants of Human Trabecular Bone Quality in Type 2 Diabetes.

CONTEXT: Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time, reports on alterations in bone tissue's material properties obtained from individuals with diabetes and known fragility fracture status. OBJECTIVE: To investigate the role of T2D in altering biomechanical, microstructural, and compositional properties of bone in individuals with fragility fracture. METHODS: Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of 2 groups, nondiabetic (n = 40) and diabetic (n = 30), with a mean duration of disease 7.5 ± 2.8 years. RESULTS: No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and postyield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in the diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications-higher total fluorescent advanced glycation end-products (fAGEs), higher nonenzymatic cross-link ratio (NE-xLR), and altered secondary structure (amide bands). There was a strong inverse correlation between NE-xLR and postyield strain, fAGEs and postyield energy, and fAGEs and toughness. CONCLUSION: The current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia's detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness indicative of increased propensity to bone fragility.

Development of HFD-Fed/Low-Dose STZ-Treated Female Sprague-Dawley Rat Model to Investigate Diabetic Bone Fragility at Different Organization Levels.

Type 2 diabetes (T2D) adversely affects the normal functioning, intrinsic material properties, and structural integrity of many tissues, and bone fragility is one of them. To simulate human T2D and to investigate diabetic bone fragility, many rodent diabetic models have been developed. Still, an outbred genetically normal nonobese diabetic rat model is not available that can better simulate the disease characteristics of nonobese T2D patients, who have a high prevalence in Asia. In this study, we used a combination treatment of high-fat diet (4 weeks, 58% kcal as fat) and low-dose streptozotocin (STZ; 35 mg/kg i.p. at the end of the fourth week) to develop T2D in female Sprague-Dawley (SD) rats. After 8 weeks of the establishment of the T2D model, the femoral bones were excised after euthanizing rats (animal age approximately 21 to 22 weeks; n = 10 with T2D, n = 10 without diabetes). The bone microstructure (µCT), mechanical, and material properties (three-point bending, cyclic reference point indentation, nanoindentation), mean mineral crystallite size (XRD), bone composition (mineral-to-matrix ratio, nonenzymatic cross-link ratio [NE-xLR], Fourier transform-infrared microspectroscopy), and total fluorescent advanced glycation end products were analyzed. We found that diabetic bone had reduced whole-bone strength and compromised structural properties (µCT). The NE-xLRs were elevated in the T2D group, and strongly and negatively correlated with postyield displacement, which suggests bone fragility was caused by a lack of glycation control. Along with that, the decreased mineral-to-matrix ratio and modulus, increased indentation distance increase, and wider mineral crystallite size in the T2D group were evidence that the diabetic bone composition and material properties had changed, and bone became weaker with a tendency to easily fracture. Altogether, this model simulates the natural history and metabolic characteristics of late-stage T2D (insulin resistance and as disease progress develops, hypoinsulinemia) for nonobese young (and/or adolescent) T2D patients (Asians) and provides potential evidence of diabetic bone fragility at various organization levels. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Investigation of diabetic patient's fingernail quality to monitor type 2 diabetes induced tissue damage.

Long-term Type 2 Diabetes (T2D) affects the normal functioning of heart, kidneys, nerves, arteries, bones, and joints. The T2D gradually alters the intrinsic material properties, and structural integrity of the tissues and prolonged hyperglycemia causes chronic damages to these tissues quality. Clinically no such technique is available which can assess the altered tissues quality associated with T2D. In the present study, the microstructural characterization (surface morphology, surface roughness and density and calcium content), material characterization (modulus, hardness), and macromolecular characterization (disulfide bond content, protein content and its secondary structure) are investigated among healthy, diabetic controlled (DC) and uncontrolled diabetic (UC) group of fingernail plate. It is found that T2D has an adverse effect on the human fingernail plate quality. The parameters of nail plate quality are changing in a pattern among all the three groups. The properties mentioned above are degrading in DC group, but the degradation is even worst in the case of severity of T2D (UC group) as compared to the healthy group (Healthy

Biomechanical Evaluation of Wasp and Honeybee Stingers.

In order to design a painless and mechanically durable micro syringe-needle system for biomedical applications, the study of insect stingers is of interest because of their elegant structures and functionalities. In the present work, the structure, mechanical properties and the mechanical behavior during insertion of wasp and honeybee stingers have been investigated. The non-invasive imaging tool, micro-computed tomography has been employed to reveal the 3D-structures of wasp and honeybee stingers. A quasi-static nanoindentation instrument was used to measure the nanomechanical properties. Both wasp and honeybee stingers have graded mechanical properties, decreasing along their longitudinal direction starting from the base. The computed tomography images and the measured material properties from nanoindentation were fed into a computational framework to determine the mechanical behavior of the stingers during penetration. The computation results predicted the penetration angle of +10° for the wasp stinger and -6° for the honeybee stinger, which mimics the practical insertion mechanism of both stingers. Based on this understanding, a wasp and honeybee stringer inspired micro syringe-needle design has also been proposed.

Knowledge, Attitude, and Practice on Menstrual Hygiene Management among School Adolescents.

BACKGROUND: Menstrual hygiene management remains a taboo in many communities in Nepal. Cultural beliefs about menstruation such as food taboos and untouchability have negative impact on dignity, health and education of adolescent girls. The objective of the study was to assess the current knowledge, attitude and practice of school adolescents on menstrual hygiene management in Doti District in Far-Western Nepal. METHODS: This cross-sectional study was carried out from October to December 2016 at seven village development committees in Doti district, Nepal. This study was done among 276 students from grade seven and eight of 11 schools. Self-administered structured questionnaire was used to obtain information from school students. Descriptive analysis was done to analyse the knowledge, attitude and practice of school adolescents on menstrual hygiene management. RESULTS: 67.4% respondents had fair knowledge and 26.4% respondents had good knowledge on menstrual hygiene management. However, out of 141 female adolescent respondents, only 56 (40%) were engaged in good menstrual hygiene practices. Around half of the respondents had positive attitude towards menstrual hygiene management related issues. CONCLUSIONS: Although knowledge on menstrual hygiene management among school adolescents is fair, still attitude and practice need to improve. Findings indicate the need of behavior change communication campaigns along with frequent reinforcement of school health education programs.

A Versatile Method for the Protection of Carbonyl Compounds by Camphor Sulfonic Acid.

BACKGROUND: Carbonyl groups are important functional groups and they play a key role in organic chemistry. This group needs to be protected in multistep synthesis against various reagents for a counter-reaction. The effort towards developing an efficient methodology for the protection of car-bonyl functional group is always a demanding reaction. The protection of carbonyl compounds for in-hibiting their chemical reactivity is an important operation in chemistry. In this paper, camphor sulfonic acid-catalysed protection of various carbonyl compounds is developed. This method is simple, envi-ronmentally friendly and yields products in high yields. METHOD: Commercially available camphor sulfonic acid is used as organo-catalyst for the protection of carbonyl functionality. This catalyst is also employed for the protection of carbonyl functionality as thi-oacetal/mixed ketal in excellent yield. The newly synthesize compounds are characterized using 1HNMR, 13C NMR and IR spectroscopy. RESULT: A diverse carbonyl functional group is protected in excellent yield under mild reaction condi-tions. CONCLUSION: We have developed an efficient organocatalysed protection method of carbonyl function-ality applicable to wide range of substrates.

Correlating Single Crystal Structure, Nanomechanical, and Bulk Compaction Behavior of Febuxostat Polymorphs.

Febuxostat exhibits unprecedented solid forms with a total of 40 polymorphs and pseudopolymorphs reported. Polymorphs differ in molecular arrangement and conformation, intermolecular interactions, and various physicochemical properties, including mechanical properties. Febuxostat Form Q (FXT Q) and Form H1 (FXT H1) were investigated for crystal structure, nanomechanical parameters, and bulk deformation behavior. FXT Q showed greater compressibility, densification, and plastic deformation as compared to FXT H1 at a given compaction pressure. Lower mechanical hardness of FXT Q (0.214 GPa) as compared to FXT H1 (0.310 GPa) was found to be consistent with greater compressibility and lower mean yield pressure (38 MPa) of FXT Q. Superior compaction behavior of FXT Q was attributed to the presence of active slip systems in crystals which offered greater plastic deformation. By virtue of greater compressibility and densification, FXT Q showed higher tabletability over FXT H1. Significant correlation was found with anticipation that the preferred orientation of molecular planes into a crystal lattice translated nanomechanical parameters to a bulk compaction process. Moreover, prediction of compactibility of materials based on true density or molecular packing should be carefully evaluated, as slip-planes may cause deviation in the structure-property relationship. This study supported how molecular level crystal structure confers a bridge between particle level nanomechanical parameters and bulk level deformation behavior.

Effect of differential surface anisotropy on performance of two plate shaped crystals of aspirin form I.

Differential surface anisotropy of different crystals of the same API can have a significant impact on their pharmaceutical performance. The present work investigated the impact of differential surface anisotropy of two plate-shaped crystals of aspirin (form I) on their hygroscopicity, stability and compaction behavior. These crystals differed in their predominant facets (100) and (001) and were coded as AE-100 & E-001. (100) facets exposed polar carbonyl groups which provided hydrophilicity to the facets. In contrast, (001) facets possessed hydrophobicity as they exposed non-polar aryl and methyl groups. Both the samples showed different degradation behavior, at various stability conditions (i.e. 40°C/75%RH, 30°C/90%RH and 30°C/60%RH) and different time intervals. Polar groups of aspirin have been reported to be prone to hydrolysis due to which AE-100 was less stable than E-001. Dynamic vapor sorption (DVS) analysis at different simulated stability conditions also supported this observation, wherein AE-100 showed higher moisture sorption than E-001. Both the samples having similar particle size, shape, surface area and hardness value, showed differences in their compactibility. However, milling narrowed down the predominance of facets and both the milled samples showed similar stability and compaction behavior. This study was also supported by surface free energy determination, molecular modeling and face indexation of unmilled and milled samples.

Influence of diene substituent position on the stereochemical outcome in IMDA reaction of decatrienones. An asymmetric synthesis of C10-epi-dihydro-epi-deoxy arteannuin B.

An asymmetric synthesis of C(10)-epi-dihydro-epi-deoxy arteannuin B is reported employing an IMDA reaction of sugar embedded decatrienone. During this investigation it has been demonstrated that changing the position of the methyl group on the diene moiety changes the stereochemical outcome leading to access to either cis- or trans-decalin derivatives exclusively.

Unprecedented influence of remote substituents on reactivity and stereoselectivity in Cu(I)-catalysed [2 + 2] photocycloaddition. An approach towards the synthesis of tricycloclavulone.

Cu(I)-catalysed [2 + 2] photocycloaddition of 1,6-dienes embedded in a furano sugar is described in connection to a synthetic approach to an abnormal marine prostanoid tricycloclavulone. An unprecedented influence of remote substituents on the reactivity and stereoselectivity of the photocycloaddition reaction has been uncovered during this investigation. While an alkene substituent inhibits cycloaddition through steric effects, a substituent having a hydroxyl or alkoxy group at the same location facilitates cycloaddition exclusively from its own side. This investigation has led to the synthesis of a functionalised 5,4-fused core unit of tricycloclavulone.

Synthesis of fused cyclic systems containing medium-sized rings through tandem ROM-RCM of norbornene derivatives embedded in a carbohydrate template.

A general approach for the synthesis of fused cyclic systems containing medium-sized rings (7-9) has been developed. The key steps involve a diastereoface-selective Diels-Alder reaction of the dienophiles 4a-d attached to a furanosugar with cyclopentadiene and ring opening (ROM)-ring closing metathesis (RCM) of the resulting norbornene derivatives 10a-d and 11a-d. Diels-Alder reaction of the dienophiles 4a-d with cyclopentadiene in the absence of a catalyst produced 10a-d as the major product arising through addition of the diene to the unhindered Si-face. The most interesting and new aspect of the Diels-Alder reaction of these dienophiles is the accessibility of the Re-face that was blocked by the alkenyl chains under Lewis acid catalysis producing the diastereoisomers 11a-d exclusively. The reversal of facial selectivity from an uncatalyzed reaction to a catalyzed one is unprecedented. The observed stereochemical dichotomy is attributed to rotation of the enone moiety along the sigma bond linking the sugar moiety during formation of the chelate 13. This makes the Re-face of the enone moiety in 4a-d unhindered. Diels-Alder reaction of the carbocyclic analogue 15 under Lewis acid catalysis produced a 1:1 mixture of the adducts 16 and 17 confirming the participation of sugar ring oxygen in chelate formation. Finally ROM-RCM of 10a-d and 11a-d with Grubbs' catalyst afforded the cis-syn-cis and cis-anti-cis bicyclo-annulated sugars 21a-d and 23a-d, respectively, containing 7-9 membered rings.