Hirdyesh Mishra

Spectroscopic and structural study of the newly synthesized heteroligand complex of copper with creatinine and urea.

Study of copper complex of creatinine and urea is very important in life science and medicine. In this paper, spectroscopic and structural study of a newly synthesized heteroligand complex of copper with creatinine and urea has been discussed. Structural studies have been carried out using DFT calculations and spectroscopic analyses were carried out by FT-IR, Raman, UV-vis absorption and fluorescence techniques. The copper complex of creatinine and the heteroligand complex were found to have much increased water solubility as compared to pure creatinine. The analysis of FT-IR and Raman spectra helps to understand the coordination properties of the two ligands and to determine the probable structure of the heteroligand complex. The LIBS spectra of the heteroligand complex reveal that the complex is free from other metal impurities. UV-visible absorption spectra and the fluorescence emission spectra of the aqueous solution of Cu-Crn-urea heteroligand complex at different solute concentrations have been analyzed and the complex is found to be rigid and stable in its monomeric form at very low concentrations.

Photochemistry of 5-aminoquinoline in protic and aprotic solvents

Photophysical properties of 5-aminoquinoline (5AQ) have been investigated in various non-polar and polar (protic and aprotic) solvents using steady state and time resolved fluorescence. In aprotic solvents, the spectral maxima depend on the polarity. However, in protic solvents both the fluorescence intensity as well decay time show decrease depending on the hydrogen bonding ability of the solvent. The results suggest that photochemistry 5AQ is quite sensitive towards the polarity as well as protic character of the solvent.

QPRTase modified N-doped carbon quantum dots: A fluorescent bioprobe for selective detection of neurotoxin quinolinic acid in human serum

Highly fluorescent nitrogen doped carbon quantum dots (NCQDs) were synthesized using microwave assisted green method. It was characterized by Transmission Electron Microscopy (TEM), FTIR, UV-Visible absorption and Photoluminiscence (PL) techniques. The NCQDs were immobilized with an enzyme named quinolinate phoshphoribosyl transferase (QPRTase). The NCQDs immobilized by QPRTase was used as a fluorescent bioprobe for the selective detection of endogenous neurotoxin quinolinic acid (QA) whose elevated level in serum is marker of many neurological disorders such as Alzheimers, Huntingtons and HIV associated dementia (HAD) as well as deficiency of vitamin B6. Steady state PL studies were carried out to measure the PL response of the fabricated fluorescent bioprobe as a function of QA concentrations in human serum samples. This probe was found applicable in linear range [3.22-51µM] with the limit of detection ~ 6.51µM. It has desirable sensitivity ~ (0.02340±0.0001) µM-1, excellent stability for ~ 7 weeks and good reproducibility. The similar response of this fluorescent bioprobe for QA detection in triple distilled water and human serum shows that it is unaffected by variation in media. Hence, this fluorescent bioprobe can be employed for QA detection in serum sample for the early detection of many diseases.

Detection of in Vitro Metabolite Formation of Leflunomide: A Fluorescence Dynamics and Electronic Structure Study

The metabolic transformation of antirheumatic fluorescent drug leflunomide into its active metabolite teriflunomide through isoxazole ring opening has been monitored in vitro using steady state and time domain fluorescence spectroscopy and density functional theory. During metabolic reaction, absorption of leflunomide split into two bands resembling absorption spectra of teriflunomide. The fluorescence spectra reveal slow conversion of leflunomide to E and Z forms of teriflunomide in aqueous medium, which becomes faster at basic pH. The E form, which is more potent as a drug, becomes more stable with an increase in the basicity of the medium. Both molecules are associated with charge transfer due to twisting in the lowest singlet excited state. Excited state charge transfer followed by proton transfer was also observed in the Z form during the ring opening of leflunomide. Quantum yield and radiative decay rates have been observed to decrease for the metabolite because of an increase in nonradiative decay channels.

Synthesis, Characterization and Photoluminescence Study of Novel Sulfobetaine Polyelectrolytes

A novel sulfobetaine copolymer is developed via polycondensation approach. The comonomers, melamine, condenses with a diketone, 5,5-dimethyl-1,3-cyclohexane (dimedone) to produce polyimine chain based on Schiff base chemistry. Dimedone-[N,N’ melaminium] propane sulfonate copolymer crystals were obtained on treatment of the polyimine with sulfopropylating agent, 1,3-propane sultone with a crosslinker, di(ethylene glycol diacrylate) (DEGDA). This crosslinked sulfobetaine polymer yielded fine needle like single crystals and shows strong blue fluorescence and a week green phosphorescence. Multi-exponential fluorescence decay function indicates the presence of different conformers both in solution and crystalline phase. This easy straightforward protocol for synthesis of crystalline, soluble, and luminescent polymer could prove to be a landmark in development of next generation smart functional materials.

A DFT study of temperature dependent dissociation mechanism of HF in HF(H2O)7 cluster

AbstractWe report a Density Functional Theoretical (DFT) study of dissociation of Hydrogen Fluoride (HF) in HF(H 2O) 7 cluster, using B3LYP functional and empirical exchange correlation functional M06-2X along with 6-31 + G(d,p) basis set. Dissociation constant, K RP, of HF dissociation and pK a values of HF in cluster at various temperatures have been reported. It has been found that both K RP and pK a are highly dependent on temperature. The variation of pK a with temperature suggests that HF is strong acid at lower temperatures. Our study also reveals that HF is a stronger acid in water cluster than in bulk water. Further, the results obtained by DFT calculations have been compared with the earlier reported results obtained from Monte Carlo (MC) simulation. It is found that DFT results are qualitatively consistent with the results of MC simulation but quantitatively different. Graphical AbstractDissociation constant, KRP of HF dissociation and pKa values of HF in cluster at various temperatures have been reported. It has been found that both KRP and pKa are highly dependent on temperature. HF is found to be a strong acid at low temperatures. Our study also reveals that HF is a stronger acid in water cluster than in bulk water. A comparison has been made between the results obtained by DFT calculations and earlier reported results of Monte Carlo (MC) simulation. It is found that DFT results are qualitatively consistent with the results of MC simulation but quantitatively different.

A density functional theory insight into the structure and reactivity of diphenyltin(IV) derivative of glycylphenylalanine

Abstract The quantum-chemical calculations based on density functional theory (DFT) have been performed on the diphenyltin(IV) derivative of glycyl-phenylalanine (H2L) at the B3LYP/6-31G(d,p)/LANL2DZ(Sn) level of theory without any symmetry constraint. The harmonic vibrational frequencies were computed at the same level of theory to find the true potential energy surface minima. The various geometrical and thermochemical parameters for the studied complex are obtained in the gas phase. The atomic charges at all the atoms were calculated using the Mulliken population analysis, the Hirshfeld population analysis, and the natural population analysis. The charge distribution within the studied complex is explained on the basis of molecular electrostatic potential maps, frontier molecular orbital analysis, and conceptual DFT-based reactivity (global and local) descriptors, using the finite difference approximation method. The nature of O-Sn, N-Sn, N→Sn, and C-Sn bonds is discussed in terms of the conceptual DFT-based reactivity descriptors. The structural analysis of the studied complex has been conducted in terms of the selected bond lengths and bond angles. The structural and the atomic charge analyses suggest a distorted trigonal bipyramidal arrangement consisting of negatively charged centers around the positively charged central Sn atom.

Evaluation of novel Saquinavir analogs for resistance mutation compatibility and potential as an HIV-Protease inhibitor drug.

A fundamental issue related to therapy of HIV-1 infection is the emergence of viral mutations which severely limits the long term efficiency of the HIV-protease (HIV-PR) inhibitors. Development of new drugs is therefore continuously needed. Chemoinformatics enables to design and discover novel molecules analogous to established drugs using computational tools and databases. Saquinavir, an anti-HIV Protease drug is administered for HIV therapy. In this work chemoinformatics tools were used to design structural analogs of Saquinavir as ligand and molecular dockings at AutoDock were performed to identify potential HIV-PR inhibitors. The analogs S1 and S2 when docked with HIV-PR had binding energies of -4.08 and -3.07 kcal/mol respectively which were similar to that for Saquinavir. The molecular docking studies revealed that the changes at N2 of Saquinavir to obtain newly designed analogs S1 (having N2 benzoyl group at N1) and S2 (having 3-oxo-3phenyl propanyl group at N2) were able to dock with HIV-PR with similar affinity as that of Saquinavir. Docking studies and computationally derived pharmacodynamic and pharmacokinetic properties׳ comparisons at ACD/I-lab establish that analog S2 has more potential to evade the problem of drug resistance mutation against HIV-1 PR subtype-A. S2 can be further developed and tested clinically as a real alternative drug for HIV-1 PR across the clades in future.