Effect on and Correlation between Particle Size, X-ray densityand Dielectric Constant, of Nanocrystalline spinel Ferrite Material due to Doping of Ni 2+, Co2+ and Cu2+ in CuCo, NiCu and CoNi respectively prepared by Sol Gel Auto Combustion Method.

Herein the preparation of ferrite materials by using chemical reactions such as SOL-GEL Auto Combustion Technique is explained and important physical and Dielectric properties of Nanocrystalline spinel ferrite material.Structural characterization of the annealed samples at400?C for 4 hours was done by using X-ray diffraction method (XRD). The single phase formation of NiCuCoFe2O4 was confirmed by X-ray diffraction analysis. The Fourier transfor InfraredRed Spectra (FT-IR) confirmed that the synthesized material is crystalline spinel ferrite. XRD revealed that the average crystalline particle size which was calculated by using Bragg’s lawand Scherer method is around 29 nm. The X-ray density is also calculated. The pellets are made from ferrite powder by using polyvinyl alcohol (PVA)as binder and by using LCR-Q meter, the Dielectric constant is calculated in the frequency range of 100Hz to5MHzat room temperature. The effect on Particle size,X-Ray Density and Dielectric Constant is observed due to doping of Ni2+ , Co2+ andCu2+ inCuCo, NiCu and CoNi respectively .The correlation ship between the Particle size, X-ray density and Dielectric Constant is discussed

Elimination of Endogenous Toxin, Creatinine from Blood Plasma Depends on Albumin Conformation: Site Specific Uremic Toxicity & Impaired Drug Binding

Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state

Pollutant-Induced Modulation in Conformation and β-Lactamase Activity of Human Serum Albumin

Structural changes in human serum albumin (HSA) induced by the pollutants 1-naphthol, 2-naphthol and 8-quinolinol were analyzed by circular dichroism, fluorescence spectroscopy and dynamic light scattering. The alteration in protein conformational stability was determined by helical content induction (from 55 to 75%) upon protein-pollutant interactions. Domain plasticity is responsible for the temperature-mediated unfolding of HSA. These findings were compared to HSA-hydrolase activity. We found that though HSA is a monomeric protein, it shows heterotropic allostericity for β-lactamase activity in the presence of pollutants, which act as K- and V-type non-essential activators. Pollutants cause conformational changes and catalytic modifications of the protein (increase in β-lactamase activity from 100 to 200%). HSA-pollutant interactions mediate other protein-ligand interactions, such as HSA-nitrocefin. Therefore, this protein can exist in different conformations with different catalytic properties depending on activator binding. This is the first report to demonstrate the catalytic allostericity of HSA through a mechanistic approach. We also show a correlation with non-microbial drug resistance as HSA is capable of self-hydrolysis of β-lactam drugs, which is further potentiated by pollutants due to conformational changes in HSA

Stereo-Selectivity of Human Serum Albumin to Enantiomeric and Isoelectronic Pollutants Dissected by Spectroscopy, Calorimetry and Bioinformatics

1–naphthol (1N), 2–naphthol (2N) and 8–quinolinol (8H) are general water pollutants. 1N and 2N are the configurational enantiomers and 8H is isoelectronic to 1N and 2N. These pollutants when ingested are transported in the blood by proteins like human serum albumin (HSA). Binding of these pollutants to HSA has been explored to elucidate the specific selectivity of molecular recognition by this multiligand binding protein. The association constants (Kb) of these pollutants to HSA were moderate (104–105 M−1). The proximity of the ligands to HSA is also revealed by their average binding distance, r, which is estimated to be in the range of 4.39–5.37 nm. The binding free energy (ΔG) in each case remains effectively the same for each site because of enthalpy–entropy compensation (EEC). The difference observed between ΔCpexp and ΔCpcalc are suggested to be caused by binding–induced flexibility changes in the HSA. Efforts are also made to elaborate the differences observed in binding isotherms obtained through multiple approaches of calorimetry, spectroscopy and bioinformatics. We suggest that difference in dissociation constants of pollutants by calorimetry, spectroscopic and computational approaches could correspond to occurrence of different set of populations of pollutants having different molecular characteristics in ground state and excited state. Furthermore, our observation of enhanced binding of pollutants (2N and 8H) in the presence of hemin signifies that ligands like hemin may enhance the storage period of these pollutants in blood that may even facilitate the ill effects of these pollutants

Speciation of Mixed-Valent Polyoxovanadate-Alkoxide Clusters (POV-Alkoxides)

The design and synthesis of tunable electroactive molecules which has wide applications as catalysts, actuators, and sensors remains one of the key challenges in synthetic chemistry. Polyoxovanadate-alkoxide clusters (POV-alkoxides) have emerged as a new class of compounds with the essential electronic and physical properties that are required for an ideal redox active material. However, the controlled synthesis of these POV-alkoxides clusters for tuning their electronic property are still an underdeveloped field largely due to lack of mechanistic insight of POV-alkoxides formation. Here, we are conducting computational researches on the speciation of a mixed-valent [V6O7(OCH3)12] POV-alkoxide clusters that can be functionalized to a redox reservoir by incorporating heterometallic species. This speciation study explores both sequential step wise cluster formation and self-assembly of trimer [VV3O3(OCH3)9] and trimer intermediate [VIV3O4(OCH3)6], [VV3O4(OCH3)9]2- for cluster formation. Our calculation shows that cluster formation through the self-assembly of building blocks favors over the sequential cluster growth of hexamer from pentamer, pentamer from tetramer and so on. Moreover, cluster containing VIV are thermodynamically more favorable compare to the clusters which has only VV. Here we will present the DFT mechanistic study of [V6O7(OCH3)12]mixed-valent POV-alkoxide cluster formation considering effect of temperature, pressure, presence of methoxy anion and reducing agent in solution as well as effect of vanadium oxidation state for the stability of clusters

COMPUTATIONAL STUDY ON THE NUCLEATION OF POLYOXOVANADATE-ALKOXIDE CLUSTERS

Polyoxovanadate-alkoxide (POV-alkoxide) clusters are a new class of electroactive species with potential electrochemical applications in redox catalysis, energy storage, and optoelectronics. These clusters\u27 redox properties can be tuned by the functionalization via heterometallic installation and changing alkoxide ligands. However, the formation mechanism of these POV-alkoxides in the solvothermal process is unknown, limiting the rational design to improve their electronic properties. This dissertation reports the speciation study of POV-alkoxide clusters, which is fundamental to controlling and manipulating the evolution of transient species during their nucleation and tuning the final product\u27s properties. Chapter 2 and chapter 3 describe our computational study of nucleation pathways of two POV-alkoxide clusters in methanol, one with only vanadium centers, [(VV6-nVIVnO6)(O)(O-CH3)12](4-n)+ and another with heterometallic iron inserted in POV-alkoxides [(VV5-nVIVnO5)(O-CH3)12(O)(FeIIICl)] (3-n)+. Our investigations show how iron heterometal incorporates into POV-alkoxides, which have paved the way for installing other heterometallic centers (Ti, Zr, or Hf). Chapter 4 explores the formation of ring-type cyclic POV-alkoxide cluster [(VIVnOn(O-R)2n)] (n=5 and 6; R = -CH3, -C2H5, and -C3H7), which is an underdeveloped field. Our calculations show that anionic directing groups (F- and Cl-) and bridging alkoxides impact cyclic POV-alkoxide clusters\u27 nucleation. Fluoride and chloride act as templating agents and stabilizers for cyclic pentamer [(VIV5O5(O-CH3)10)F]- and hexamer [(VIV6O6(O-CH3)12)Cl]- formation. Without halides, methoxide, ethoxide, and n-propoxide bridging ligands favor the formation of the cyclic hexamer [(VIV6O6(O-R)12)] (R = -CH3, -C2H5, and -C3H7), while isopropoxide favors the formation of cyclic pentamer [(VIV5O5(O-R)10)]. We predict the expansion of cyclic POV-alkoxide motifs by the possibility of isolating cyclic pentameric [(VIV5O5(O-CH3)12)F]- with fluoride template and cyclic pentameric [(VIV5O5(O-C3H7)12)] through isopropoxide ligand functionalization in future

Use of Peptides for the Management of Alzheimer’s Disease: Diagnosis and Inhibition

Alzheimer’s disease (AD) is a form of dementia and the most common progressive neurodegenerative disease (ND). The targeting of amyloid-beta (Aβ) aggregation is one of the most widely used strategies to manage AD, and efforts are being made globally to develop peptide-based compounds for the early diagnosis and treatment of AD. Here, we briefly discuss the use of peptide-based compounds for the early diagnosis and treatment of AD and the use of peptide-based inhibitors targeting various Aβ aggregation checkpoints. In addition, we briefly discuss recent applications of peptide-based inhibitors against various AD targets including amyloid beta, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tyrosine phosphatase (TP) and potassium channel KV1.3

Synthesis and Characterization of Porous Benzimidazole-Linked Polymers and Their Performance in Small Gas Storage and Selective Uptake

Porous organic polymers containing nitrogen-rich building units are among the most promising materials for selective CO₂ capture and separation which can have a tangible impact on the environment and clean energy applications. Herein we report on the synthesis and characterization of four new porous benzimidazole-linked polymers (BILPs) and evaluate their performance in small gas storage (H₂, CH₄, CO₂) and selective CO₂ binding over N₂ and CH₄. BILPs were synthesized in good yields by the condensation reaction between aryl-<i>o</i>-diamine and aryl-aldehyde building blocks. The resulting BILPs exhibit moderate surface area (SA_BET = 599–1306 m² g^–1), high chemical and thermal stability, and remarkable gas uptake and selectivity. The highest selectivity based on initial slope calculations at 273 K was observed for BILP-2: CO₂/N₂ (113) and CO₂/CH₄ (17), while the highest storage capacity was recorded for BILP-4: CO₂ (24 wt % at 273 K and 1 bar) and H₂ (2.3 wt % at 77 K and 1 bar). These selectivities and gas uptakes are among the highest by porous organic polymers known to date which in addition to the remarkable chemical and physical stability of BILPs make this class of material very promising for future use in gas storage and separation applications

Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and <i>In Silico</i> Approaches

Cyclobenzaprine hydrochloride (CBH) is a well-known muscle relaxant that is widely used to relieve muscle spasms and other pain associated with acute musculoskeletal conditions. In this study, we elucidated the binding characteristics of this muscle relaxant to human serum albumin (HSA). From a pharmaceutical and biochemical viewpoint, insight into the structure, functions, dynamics, and features of HSA-CBH complex holds great importance. The binding of CBH with this major circulatory transport protein was studied using a combination of biophysical approaches such as UV-VIS absorption, fluorescence quenching, and circular dichroism (CD) spectroscopy. Various in silico techniques, molecular docking and molecular dynamics, were also used to gain deeper insight into the binding. A reduction in the fluorescence intensities of HSA-CBH complex with a constant increase in temperature, revealed the static mode of protein fluorescence quenching upon CBH addition, which confirmed the formation of the HSA-CBH ground state complex. The alteration in the UV-VIS and far-UV CD spectrum indicated changes in both secondary and tertiary structures of HSA upon binding of CBH, further proving CBH binding to HSA. The analysis of thermodynamic parameters ∆H&#176; and ∆S&#176; showed that binding of CBH to HSA was dominated by intermolecular hydrophobic forces. The results of the molecular docking and molecular dynamics simulation studies also confirmed the stability of the complex and supported the experimental results