Cobalt(III)-Catalyzed C-6 Alkenylation of 2-Pyridones by Using Terminal Alkyne with High Regioselectivity.

Co(III)-catalyzed alkenylation of 2-pyridones by using terminal alkyne as a reaction partner with high regioselectivity has been demonstrated for the first time. The reaction conditions are mild and compatible with a wide range of substrate combinations. It also shows good functional group tolerance. It proceeds through cyclometalation followed by alkyne insertion and protodemetalation steps. The formation of five- and seven-membered cobaltacycle intermediates was also detected through high-resolution mass spectrometry.

Chitosan Engineered PAMAM Dendrimers as Nanoconstructs for the Enhanced Anti-Cancer Potential and Improved In vivo Brain Pharmacokinetics of Temozolomide.

PURPOSE: To establish a platform for the possibility of effective and safe delivery of Temozolomide (TMZ) to brain via surface engineered (polyamidoamine) PAMAM dendrimer for the treatment of glioblastoma. METHODS: The present study aims to investigate the efficacy of PAMAM-chitosan conjugate based TMZ nanoformulation (PCT) against gliomas in vitro as well as in vivo. The prepared nanoconjugated formulation was characterized by 1H NMR, FT-IR spectroscopy and for surface morphological parameters. The reported approach was also designed in such a way to ensure toxicity before in vivo delivery through conducting the hemolytic study. RESULT: Surface morphology was found as per nanoformulation via size, pdi and zeta potential measurement. PCT was more efficacious in terms of IC50 values compared to pure TMZ against U-251 and T-98G glioma cell lines. The in vivo pharmacokinetic parameters proved sustained release fashion such as half-life (t1/2) of 22.74 h (PCT) rather than15.35 h (TMZ) only. Higher concentration was found in heart than brain in bio-distribution studies. This study exhibits the potential applicability of dendrimer and CS in improving the anticancer activity and delivery of TMZ to brain. CONCLUSION: The attractive ex vivo cytotoxicity against two glioma cell lines; U-251 and T-98G and phase solubility studies of TMZ revealed remarkable results. In vivo studies of prepared nanoformulation were significant and promising that explored the double concentration of TMZ in brain due to surface functionality of dendrimer. The reported work is novel and non- obvious as none of such approaches using chitosan anchored dendrimer for TMZ delivery has been reported earlier.

Data analytics and modelling in context to determination of moisture susceptibility of reclaimed asphalt foamed bituminous mix.

The presence of water badly affects the moisture susceptibility of the reclaimed asphalt Foamed Bituminous Mix (FBM). The present study is mainly emphasized to assess the moisture susceptibility of reclaimed asphalt FBM, Where RAP is being incorporated as a replacement of fresh aggregates. Moisture susceptibility of the mix is evaluated in terms of tensile strength ratio (TSR) and resilient modulus ratio, subjected to different conditioning procedures namely AASHTO T283, modified IDOT, TG-2 guidelines, and MIST. Further data analytics and regression modeling are also carried out to determine the moisture susceptibility of the mix and to check the statistics among the variables. The findings show that the incorporation of RAP in the FBM improves moisture resistance. Further, FBM containing 100% RAP shows the least moisture susceptibility in terms of TSR and Mr ratio irrespective of any conditioning type. Moreover, MIST conditioning may be preferred to assess the moisture sensitivity as it simulates the field pore pressure effects. Further, mathematical analysis is carried out to predict the moisture susceptibility of mix. Adjusted R square coefficient indicates a better fit of the prediction model developed. Overall, the study may be helpful to highway professionals in analyzing the conditioning procedures and determining the moisture sensitivity of the reclaimed asphalt Foamed Bituminous Mix.

Two Cases of Ipsilateral Posterior Hip Dislocation and Shaft Femur Fracture and Management.

Introduction: The incidence of ipsilateral fracture of the shaft of the femur and dislocation of the hip are extremely rare injuries. However, the incidence of complex fractures is increasing day by day due to an increasing variety of traumatic mechanisms. This type of injury constitutes various diagnostic and treatment difficulties for the surgeon. Such injuries should be managed on an urgent basis for better functional outcomes. Case Report: We hereby describe two such cases: First case hip was reduced using external fixator pins, stabilization of the shaft femur fracture was done with an external fixator and the second case hip was reduced with bone holding clamps and the shaft femur fracture was fixed with interlocking nail. Conclusion: Fixator-assisted closed reductions are the first line of treatment in the management of posterior dislocation hip complicated with ipsilateral femoral shaft fractures. If closed reduction fails, fracture site can be opened and direct forces can be applied to the proximal femur to aid hip reduction with minimum complications.

Ipsilateral Knee Dislocation and Ankle Fracture Dislocation.

Introduction: A dislocated knee is a potential limb-threatening injury. Simultaneous dislocation of knee and ankle joint in an ipsilateral limb is a very rare pattern of injury. A few cases of ipsilateral hip and knee dislocation were described in literature. Rare injury such as posterior dislocation knee with ipsilateral ankle fracture dislocation cases was also presented. However, lateral dislocation of knee along with the same side ankle fracture dislocation is a rare scenario. To the best of our knowledge, these two simultaneous lesions do not seem to have been reported previously. Immediate management of such injury is to reduce both joint and stabilization with external fixator and definitive surgery in the second stage when soft-tissue condition allows. Case Report: We describe a rare case of a 37-year-old farmer having injury to his right leg with tiller machine. Lateral right knee dislocation and right ankle fracture dislocation reduced in the emergency department. In emergency OT, external fixator applied for knee and ankle stabilization. When swelling subsides in ankle, fracture fixation is done with plates and screws. Knee fixator is kept for 6 weeks then knee physiotherapy started. Conclusion: Dislocation of any joint is treated as an orthopedic emergency. Simultaneous dislocation of knee and ankle joints in an ipsilateral limb is a challenging situation for even the experienced surgeon. The outcome of such patients varies with associated injuries and time took for relocation and meticulous physical examination, with a high index of clinical suspicion is needed in diagnosing and management of such cases.

Effect of feeding different proportions of groundnut haulms (Arachis hypogaea) and cluster bean straw (Cyamopsis tetragonoloba) on nutrient utilisation and serum biochemical parameters in dromedary camels.

The effect of feeding different proportions of groundnut haulms (Arachis hypogaea) and cluster bean straw (Cyamopsis tetragonoloba) on nutrient digestibility, nutritive value, nutrient intake and serum biochemical parameters was studied using nine male dromedary camels of Bikaneri breeds (637.5 kg average body weight; 8-9 years of age). Groundnut haulms (GNH) and cluster bean straw (CBS) were fed in one of three ratios, 75:25, 50:50 and 25:75 in treatments T(1), T(2) and T(3), respectively. In all treatments, concentrate mixture was fed as per requirement of the camels. The groundnut haulms were more nutritive as compared to the cluster bean straw. The nutrient digestibility of dry matter, organic matter, crude protein (CP), crude fibre and acid detergent fibre was better in T(1) than T(2) and T(3). Likewise, the CP, digestible crude protein and total digestible nutrient contents were significantly higher in T(1) followed by T(2) and T(3). There was non-significant affect on average daily gain of camels. However, dry matter intake, digestible crude protein intake and total digestible nutrients were better in T(1) as compared to T(2) and T(3). The total water intake per kilogram of dry matter intake (litres) was 2.98, 2.89 and 2.68, respectively, in T(1), T(2) and T(3). The camels in all the treatments were in positive nitrogen, calcium and phosphorus balance. The treatments had a significant effect on serum biochemical parameters like glucose, cholesterol, aspartate transaminase and creatinine. The results may conclude that feeding of higher proportion of groundnut haulms as compared to cluster bean straw has pronounced improvement in nutritional utilisation by the camels.

Development and standardization of a COVID-19 Vaccination Anxiety scale for Adult Urban Indian Population (CVAS-A).

Given the ongoing COVID-19 vaccination drive across the globe, a significant amount of confusion, mistrust, misunderstanding, and hesitancy had surfaced regarding the vaccine. A standardized tool to understand the possible reasons of COVID-19 vaccination anxiety and hesitancy would be valuable in this context. The current study aimed at developing a standardized tool to measure COVID-19 Vaccination Anxiety among Urban Indian adults. A 19-item scale was administered to an Urban adult Indian population (N = 760) between the period of February 2021- May 2021 to obtain factors associated with COVID-19 Vaccination Anxiety and establish reliability estimates of the scale. Infection-related anxiety, information-related anxiety and vaccine side-effect-related anxiety were the three factors determined through Factor Analysis. The scale was validated with Convergent and Discriminant Validity by finding correlation between the three factors of the scale and five factors of the Brief version of the Big-Five personality Inventory (extraversion, agreeableness, openness to experience, conscientiousness, and neuroticism). It is expected that a tool such as CVAS-A would help in understanding and managing COVID-19-related vaccination hesitancy.

Spectroscopic studies on chromium(III), manganese(II), cobalt(II), nickel(II) and copper(II) complexes with hexadentate nitrogen-sulfur donor [N(2)S(4)] macrocyclic ligand.

Complexes of transition metals have been synthesized with hexadentate ligand (2,6-bis(((2-mercaptophenyl)thio)methyl)pyridinato)metal(II). These complexes have been synthesized via the two step template reaction by using the benzene dithiol, 2,6-bis(chloro)methyl pyridine and corresponding metal salt as key raw materials. The structures of the complexes have been elucidated on the basis of elemental analysis, molar conductance measurements, magnetic susceptibility measurements, IR, electronic and EPR spectral studies. All of the complexes were found to possess six-coordinated geometry and are of high spin type.

Spectroscopy: the study of DNA cleavage by newly synthesized polydentate macrocyclic ligand and its copper(II) complexes.

A novel hexadentate nitrogen donor [N6] macrocyclic ligand, i.e. 2,6,12,16,21,22-hexaaza-3,5,13,15-tetramethyl-4,14-diethyl-tricyclo-[15.3.1.1(7-11)]docosane-1(21),2,5,7(22),8,10,12,15,17,19-decaene (L), has been synthesized. Copper(II) complexes with this ligand have been prepared and subjected to elemental analyses, molar conductance measurements, magnetic susceptibility measurements, mass, 1H NMR (ligand), IR, electronic, and EPR spectral studies. On the basis of molar conductance the complexes may be formulated as [Cu(L)X2] [X = Cl(-), Br(-), NO3(-) and CH3COO(-)] due to their nonelectrolytic nature in N,N'-dimethylformamide (DMF). All the complexes are of the high spin type and are six coordinated. On the basis of IR, electronic and EPR spectral studies tetragonal geometry has been assigned to the Cu(II) complexes. The interaction of these complexes with calf thymus DNA has been explored by using absorption, emission, viscosity measurements, electrochemical studies and DNA cleavage. All the experimental results suggest that the complexes bind to DNA and also promote the cleavage plasmid pBR 322, in the presence of H2O2 and ascorbic acid.

The Spectroscopy: a modern technology in the characterization of novel macrocyclic ligand and its homo-bi-nuclear cobalt (II) complexes.

A novel hexadentate nitrogen-sulphur donor [N(4)S(2)] macrocyclic ligand, i.e. 3,13-dithio-6,10,16,20-tetraoxo-8,18-dithia-1,2,4,5,11,12,14,15-octaazacyclocosane (L), has been synthesized. Cobalt (II) complexes of this ligand have been prepared and subjected to elemental analyses, molar conductance measurements, magnetic moment susceptibility measurements, mass, (1)H NMR (Ligand), IR, electronic, and EPR spectral studies. On the basis of molar conductance, complexes may be formulated as [Co(2)(L)X(2)]X(2) [where X=Cl(-), Br(-), NO(3)(-) and NCS(-)] due to their 1:2 electrolytic nature in dimethylformamide (DMF). All the complexes are of the high spin type and are four coordinated. On the basis of IR, electronic and EPR spectral studies tetrahedral geometry has been assigned to all the complexes. The antimicrobial activities of the ligand and its complexes, as growth inhibiting agents, have been screened in vitro against several species of bacteria and plant pathogenic fungi.

Spectroscopic and physicochemical studies on nickel(II) complexes of isatin-3,2'-quinolyl-hydrazones and their adducts.

Nickel(II) complexes of isatin-3,2'-quinolyl-hydrazones of the type [Ni(L)X] (where X=Cl-, Br-, NO3-, CH3COO- and ClO4-] and their adducts Ni(L)X.2Y [where Y=pyridine or dioxane and X=Cl-, Br-, NO3- and ClO4-] have been synthesized under controlled experimental conditions and characterized by using the modern spectroscopic and physicochemical techniques viz. mass, 1H NMR, IR, electronic, elemental analysis, magnetic moment susceptibility measurements and molar conductance, etc. On the basis of spectral studies a four coordinated tetrahedral geometry is assigned for Ni(L)X type complexes whereas the adducts (Ni(L)X.2Y) were found to have a six coordinated distorted octahedral geometry.

Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules.

Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed.

Dendrimer encapsulated and conjugated delivery of berberine: A novel approach mitigating toxicity and improving in vivo pharmacokinetics.

Berberine (BBR) is a nitrogenous cyclic natural alkaloid with potential anticancer activity. However it has been less explored due to its poor pharmacokinetic profile. Dendrimers (e.g. PAMAM) have promising potential to deliver anticancer drugs/bio-actives because of their well-defined architecture, monodispersity and tailor-made surface functionality. In the present study it was attempted to deliver berberine through G4 PAMAM dendrimers by conjugation (BPC) as well as encapsulation (BPE) approach. The developed encapsulated and conjugated berberine formulations were found to have size in the approximate range of 100-200nm while zeta potential was almost same as PAMAM G4 dendrimer. The entrapment efficiency in BPE was found to be 29.9%, whereas, the percentage conjugation in BPC was found to be 37.49% indicating high drug payload in conjugation. The developed nano-formulations were characterized through 1H NMR, FT-IR as well as electron microscopy (SEM and TEM). The in vitro release study in different media (water and PBS 7.4) showed sustained release pattern of BBR. Almost 72% and 98% drug was released within 24h respectively; whereas in PBS almost 80% and 98% release was observed within 24h, respectively. The formulations followed Higuchi release and first order release as best fit release kinetic model. MTT assay results showed significantly higher anticancer activity for the PAMAM-BBR (BPC) (p<0.01) against MCF-7 and MDA-MB-468 breast cancer cells. The time dependent ex vivo hemolytic toxicity of the BPC and BPE was significantly less (<5%) even after 24h, which indicated that the formulations can be regarded as significantly safe and biocompatible. Similarly, the in vivo hematological parameters were analyzed through auto-analyzer and the formulations were found to be safer and biocompatible with very least but insignificant (p>0.05) effects. The in vivo pharmacokinetic parameters were found to be impressively improved in albino rat model. The pharmacokinetic parameters such as half-life (t1/2) and AUC of berberine were impressively improved in the plasma level time in vivo studies in albino rat model. The obtained t1/2 was 14.33h for BPC compared to 6.7h for BBR alone. The overall conclusion says that among both the developed formulations the conjugated formulation (BPC) was found to be more prominent than the encapsulated one (BPE). Therefore conclusively conjugation can be a better option for the delivery of natural bio-actives through dendrimers.

Spectroscopic characterization and EPR spectral studies on transition metal complexes with a novel tetradentate, 12-membered macrocyclic ligand.

Complexes of Cr(III), Mn(II), Co(II), Ni(II) and Cu(II) containing a tetradentate macrocyclic N-donor ligand have been prepared via template reaction of 2,3-pentanedione, ethylene-di-ammine and transition metal ions. The complexes have been characterized on the basis of the elemental analysis, molar conductance, magnetic moment susceptibility, IR, electronic and EPR spectral studies. The complexes are of high spin type and possess four coordinate tetrahedral five coordinate square pyramidal and six coordinated octahedral/tetragonal geometry.

Spectroscopic approach in the characterization of the copper(II) complexes of isatin-3,2'-quinolyl-hydrazones and their adducts.

Copper(II) complexes of isatin-3,2'-quinolyl-hydrazones of the type [Cu(L)X] (where X=Cl(-), Br(-), NO(3)(-), CH(3)COO(-) and ClO(4)(-)] and their adducts Cu(L)X.2Y [where Y=pyridine or dioxane and X=Cl(-), Br(-), NO(3)(-) and ClO(4)(-)] have been synthesized under controlled experimental conditions and characterized by using the modern spectroscopic and physicochemical techniques viz. IR, electronic, EPR, elemental analysis, magnetic moment susceptibility measurements and molar conductance, etc. On the basis of spectral studies a four coordinated square planer geometry is assigned for Cu(L)X type complexes whereas the adducts (Cu(L)X.2Y were found to have a six coordinated octahedral geometry.

PLGA Nanoparticles and Their Versatile Role in Anticancer Drug Delivery.

Nanotechnological advancement has become a key standard for the diagnosis and treatment of several complex disorders such as cancer by utilizing the enhanced permeability and retention effect and tumor-specific targeting. Synthesis and designing the formulation of active agents in terms of their efficient delivery is of prime importance for healthcare. The use of nanocarriers has resolved the undesirable characteristics of anticancer drugs such as low solubility and poor permeability in cells. Several types of nanoparticles (NPs) have been designed with the use of various polymers along or devoid of surface engineering for targeting tumor cells. All NPs include polymers in their framework and, of these, polylactide-co-glycolide (PLGA) is biodegradable and Food and Drug Administration approved for human use. PLGA has been used extensively in the development of NPs for anticancer drug delivery. The extensive use of PLGA NPs is promising for cancer therapy, with higher efficiency and less adverse effects. The present review focused on recent developments regarding PLGA NPs, the methods used for their preparation, their characterization, and their utility in the delivery of chemotherapeutic agents.

EPR, mass, IR, electronic, and magnetic studies on copper(II) complexes of semicarbazones and thiosemicarbazones.

Copper(II) complexes having the general composition Cu(L)(2)X(2) [where L = isopropyl methyl ketone semicarbazone (LLA), isopropyl methyl ketone thiosemicarbazone (LLB), 4-aminoacetophenone semicarbazone (LLC), and 4-aminoacetophenone thiosemicarbazone (LLD) and X = Cl(-), 1/2SO(4)(2-)] have been synthesized. All the Cu(II) complexes reported here have been characterized by elemental analyses, molar conductance, magnetic moment susceptibility, EI mass, (1)H NMR, IR, EPR, and electronic spectral studies. All the complexes were found to have magnetic moments corresponding to one unpaired electrons. The possible geometries of the complexes were assigned on the basis of EPR, electronic, and infrared spectral studies.

Spectroscopic approach in characterization of chromium(III), manganese(II), iron(III) and copper(II) complexes with a nitrogen donor tetradentate, 14-membered azamacrocyclic ligand.

The complexes of Cr(III), Mn(II), Fe(III) and Cu(II) were synthesized with the macrocyclic ligand i.e. 2,3,9,10-tetraketo-1,4,8,11-tetraazacyclotetradecane. The ligand was prepared by the [2 + 2] condensation reaction of diethyloxalate and 1,3-diamino propane. These complexes were found to have the general composition M(L)X3 and M'(L)X2 [where M = Mn(II) and Cu(II), M' = Cr(III) and Fe(III), L = ligand (N4) and X = Cl-, NO3-, 1/2SO4(2-) and [CH3COO-]. The ligand and its transition metal complexes were characterized by the elemental analyses, molar conductance, magnetic susceptibility, mass, IR, electronic, and EPR spectral studies. On the basis of IR, electronic and EPR spectral studies an octahedral geometry has been assigned for Cr(III), Mn(II) and Fe(III) and a tetragonal geometry for Cu(II) complexes.

Spectroscopic evaluation of manganese(II) complexes derived from semicarbazones and thiosemicarbazones.

Manganese(II) complexes having the general composition Mn(L)2X2 [where L=isopropyl methyl ketone semicarbazone (LLA), isopropyl methyl ketone thiosemicarbazone (LLB), 4-aminoacetophenone semicarbazone (LLC) and 4-aminoacetophenone thiosemicarbazone (LLD) and X=Cl-, 1/2SO(4)2-] have been synthesized. All the complexes were characterized by elemental analyses, molar conductance, magnetic moment susceptibility, EI-mass, 1H NMR, IR, EPR and electronic spectral studies. All the complexes show magnetic moments corresponding to five unpaired electrons. The possible geometries of the complexes were assigned on the basis of EPR, electronic and infrared spectral studies.

Mass, EPR, IR and electronic spectroscopic studies on newly synthesized macrocyclic ligand and its transition metal complexes.

Manganese(II), cobalt(II), nickel(II) and copper(II) complexes have been synthesized with a new tetradentate ligand viz. 1,3,7,9-tetraaza-2,4,8,10-tetraketo-6,12-diphenyl-cyclododecane (L) and characterized by the elemental analysis, molar conductance measurements, magnetic susceptibility measurements, mass, 1H NMR, IR, electronic and EPR spectral studies. The molar conductance measurements of the complexes in DMF correspond to be nonelectrolytic nature for Mn(II), Co(II) and Cu(II) while 1:2 electrolytes for Ni(II) complexes. Thus, these complexes may be formulated as [M(L)X2] and [Ni(L)]X2 (where M=Mn(II), Co(II) and Cu(II) and X=Cl- and NO3-). On the basis of IR, electronic and EPR spectral studies an octahedral geometry has been assigned for Mn(II) and Co(II) complexes, square-planar for Ni(II) whereas tetragonal for Cu(II) complexes. The ligand and its complexes were also evaluated against the growth of bacteria and pathogenic fungi in vitro.