Quantum Chemical Calculation and DFT Study of Sitagliptin: Insight from Computational Evaluation and Docking Approach (original) (raw)
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Molecular structure, spectral investigation (1 H NMR, 13 C NMR, UV–Visible, FT-IR, FT-Raman), NBO, intramolecular hydrogen bonding, chemical reactivity and first hyperpolarizability analysis of formononetin [7-hydroxy-3(4-methoxyphenyl)chromone]: A quantum chemical study A combined theoretical and experimental approach is used to study the properties of formononetin. FT-Raman and FT-IR spectra were recorded in the solid phase, and interpreted in terms of PED analysis. The computational results diagnose the most stable conformer of formononetin. Chemical reactivity has been measured by reactivity descriptors and MEP. The existence of intramolecular H-bonds is investigated on the basis of AIM theory and NBO analysis. g r a p h i c a l a b s t r a c t a b s t r a c t Formononetin [7-hydroxy-3(4-methoxyphenyl)chromone or 4 0-methoxy daidzein] is a soy isoflavonoid that is found abundantly in traditional Chinese medicine Astragalus mongholicus (Bunge) and Trifolium pretense L. (red clover), and in an Indian medicinal plant, Butea (B.) monosperma. Crude extract of B. mono-sperma is used for rapid healing of fracture in Indian traditional medicine. In this study, a combined theoretical and experimental approach is used to study the properties of formononetin. The optimized geometry was calculated by B3LYP method using 6-311++G(d,p) as a large basis set. The FT-Raman and FT-IR spectra were recorded in the solid phase, and interpreted in terms of potential energy distribution (PED) analysis. Density functional theory (DFT) is applied to explore the nonlinear optical properties of the molecule. Good consistency is found between the calculated results and observed data for the electronic absorption, IR and Raman spectra. The solvent effects have been calculated using time-dependent density functional theory in combination with the integral equation formalism polarized continuum model, and the results are in good agreement with observed measurements. The double well potential energy curve of the molecule about the respective bonds, have been plotted, as obtained from DFT/6-31G basis set. The computational results diagnose the most stable conformer of formononetin. The HOMO–LUMO energy gap of possible conformers has been calculated for comparing their chemical activity. Chemical reactivity has been measured by reactivity descriptors and molecular electrostatic potential
The solid phase FT-IR and FT-Raman spectra of Gliptus {(2S)-1-[2-[(3-hydroxy-1-adamantyl) amino] acetyl] pyrrolidine-2-carbonitrile} have been recorded in the regions 4000–400 cm−1 and 3500-50 cm−1, respectively. To interpret the experimental data, ab initio computations of the vibrational frequencies were carried out using the Gaussian 03 program followed by the full optimizations done using Density Functional Theory (DFT) at B3LYP/6-31G(d,p) level. The combined use of experiments and computations allowed a firm assignment of the majority of observed bands for the compound. The calculated stretching frequencies have been found to be in good agreement with the experimental frequencies. The electronic and charge transfer properties have been explained on the basis of Highest Occupied Molecular Orbitals (HOMOs), Lowest Unoccupied Molecular Orbitals (LUMOs). From the optimized geometry of the molecule, Molecular Electrostatic Potential (MEP) of the title compound have been calculated. The theoretical results showed good agreement with the experimental values. The molecular modelings are drawn and showed the bond length, bond angle, chemical reactivity, energy components (kcal/mol) and binding energy (kcal/mol) for all the title compounds and also protein for the ligand is shown. The study suggests further investigation on Gliptus for their biological activity importance.
Solid-State Characterization of Different Crystalline Forms of Sitagliptin
Materials
Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-4, used for the treatment of type 2 diabetes mellitus. The crystal structure of active pharmaceutical solids determines their physical and chemical properties. The polymorphism, solvates and hydrates can influence the free energy, thermodynamic parameters, solubility, solid-state stability, processability and dissolution rate, besides directly affecting the bioavailability. Thus, the physicochemical characterization of an active pharmaceutical ingredient is required to guarantee the rational development of new dosage forms. In this context, we describe herein the solid-state characterization of three crystalline forms of sitagliptin: sitagliptin phosphate monohydrate, sitagliptin phosphate anhydrous and sitagliptin base form. The investigation was carried out using differential scanning calorimetry (DSC), thermogravimetry (TG)/derivative thermogravimetry (DTG), spectroscopic techniques, X-ray powder diffraction (XRPD) an...
Journal of Advanced Scientific Research
Migalastat (Galafold) is a pharmacological chaperone indicated for the long term treatment for fabry disease a rare genetic disorder in adults. Quantum chemical calculations of energy, geometrical shape and vibrational wavenumbers of Migalastat have been accomplished by the usage of DFT method. The specific exploration of the infrared spectra of the compound underneath have a look at is centered on potential energy distribution (PED). Dipole moment, polarizability and first order static hyperpolarizability calculation using DFT/B3LYP/6-311G(d,p) level of theory outlined the nonlinear optical behavior of the underlying molecule. The frontier molecular orbitals and molecular electrostatic potential map were additionally given to clarify the molecular characteristics of the compound. To show the chemical activity of the chemical compound, reactivity descriptors and thermodynamic properties were also calculated utilizing 6-311G(d,p) basis set. Electron density distribution on atoms and ...
Organic Letters, 2015
The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate SO, consistent with MsOH being crucial for high selectivity. The second is a novel C−H•••F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.
Conformational study of arbutin by quantum chemical calculations and multivariate analysis
Journal of Molecular Structure, 2010
A conformational study of the molecule of arbutin (4-hydroxyphenyl-b-D-glucopyranoside) has been undertaken. The molecule is composed by a glucopyranoside moiety bound to a phenol ring. It has eight conformationally relevant dihedral angles, five of them related with the orientation of the hydroxyl groups and the remaining three taking part in the skeleton of the molecule. A systematic search on the conformational space of arbutin was performed using molecular orbital methods, followed by the identification of structural similarities between the different conformers, using multivariate analyses. This approach allowed the grouping of conformers according to their structural affinity and the establishment of correlations between their structures and several properties. Intramolecular interactions involving OH groups were also investigated and correlations between spectroscopic, structural and thermodynamic properties established. The developed strategy might be useful to investigate the structure and structure/properties correlations in other conformationally flexible molecules. . Conformations with energies lower than 50 kJ mol À1 were stored while higher-energy conformations or duplicate structures were discarded. The structures obtained from this conformational search were used as start points for the construction of the input files later used in the higher level quantum chemical calculations. These latter were performed with Gaussian 03 [12] at the DFT level of theory, using the 6-311++G(d,p) basis set [13] and the three-parameter density hybrid
The solid phase FT-IR and FT-Raman spectra of Ebilfumin have been recorded in the regions 4000–400 cm −1 and 3500-50 cm −1 respectively. To interpret the experimental data, ab initio computations of the vibrational frequencies were carried out using the Gaussian 03 program followed by the full optimizations done using Density Functional Theory (DFT) at B3LYP/6-31G(d,p) level. The combined use of experiments and computations allowed a firm assignment of the majority of observed bands for the compound. The calculated stretching frequencies have been found to be in good agreement with the experimental frequencies. The electronic and charge transfer properties have been explained on the basis of Highest Occupied Molecular Orbitals (HOMOs), Lowest Unoccupied Molecular Orbitals (LUMOs). From the optimized geometry of the molecule, Molecular Electrostatic Potential (MEP) distributions of the title compound have been calculated in the ground state theoretically. The theoretical results showed good agreement with the experimental values. The molecular modelings are drawn and showed the bond length, bond angle, chemical reactivity, energy components (kcal/mol) and binding energy (kcal/mol) for all the title compounds and also protein for the ligand is shown. The study suggests further investigation on Ebilfumin for their biological activity importance.
H and 13 C NMR AIM a b s t r a c t The conformational and hydrogen bonding studies of genistein have been performed by combined spectroscopic and quantum chemical approach. The vibrational spectra (FT-IR and FT-Raman), UV evisible and 1 H and 13 C NMR absorption spectra of genistein have been recorded and examined. The vibrational wavenumbers of optimized geometry and total energy for isolated molecule and hydrogen-bonded dimers of genistein have been determined using the quantum chemical calculation (DFT/B3LYP) with extended 6e311þþG (d,p) basis set. The vibrational assignments for the observed FT-IR and FT-Raman spectra of genistein are provided by calculations on monomer and hydrogen-bonded dimer. The quantum theory of atoms in molecules (QTAIM) is used for investigating the nature and strength of hydrogen-bonds. UVevisible spectrum of the genistein was recorded in methanol solvent and the electronic properties were calculated by using time-dependent density functional theory (TDeDFT). The computed HOMO and LUMO energies predicted the type of transition as p / p*. The 1 H and 13 C NMR signals of the genistein were computed by the Gauge including atomic orbital (GIAO) approach. Natural bond orbital (NBO) analysis predicted the stability of molecules due to charge delocalization and hyper conjugative interactions. NBO analysis shows that there is an OeH/O inter and intramolecular hydrogen bond, and p / p* transition in the monomer and dimer, which is consistent with the conclusion obtained by the investigation of molecular structure and assignment of UVevisible spectra.
Ampicillin trihydrate chemically associated with the empirical formula C 16 H 19 N 3 O 4 SÁ3H 2 O, is a semi-synthetic amino-penicillin derived from the elementary penicillin nucleus, 6-aminopenicillanic acid. It is a very common antibiotic that is active against an extensive range of Gram-positive and Gram-negative organisms. It is used to treat certain varieties of bacterial infections, like gonorrhea and infections of the urinary, intestinal and respiratory tracts. In the present effort, quantum chemical calculations of molecular geometries (bond lengths and bond angles) and bonding features of the monomer and dimer of ampicillin trihydrate in the ground state have been carried out due to its biological and industrial importance. The optimized geometry and wavenumber of the vibrational bands of the molecule have been calculated by ab initio density functional theory (DFT) using Becke's three-parameter hybrid functional (B3LYP) with a 6-311++G(d,p) basis set. Vibrational wavenumbers were compared with the observed FT-Raman and FT-IR spectra. Molecular electrostatic potential (MEP) has also been plotted for predicting the molecule reactivity towards positively or negatively charged reactants and it shows that electropositive potential is visualized in the vicinity of the-NH 3 + group and the electropositive region is found near the H 2 O molecule in both monomer and dimer. HOMO-LUMO analysis has been done to describe the way the molecule interacts with other species. Natural bond orbital (NBO) analysis has been carried out to inspect the intra-and inter-molecular hydrogen-bonding, conjugative and hyperconjugative interactions and their second order stabilization energy E (2). Nonlinear optical (NLO) analysis has also been performed to study the non-linear optical properties of the molecule by computing the first hyperpolarizability (b 0). The variation of thermo-dynamic properties with temperature has been studied. Topological parameters at bond critical points (BCP) have been evaluated by 'Quantum theory of atoms in molecules' (QTAIM).
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 2013
Gabapentin (GP), structurally related to the neurotransmitter GABA (gamma-aminobutyric acid), mimics the activity of GABA and is also widely used in neurology for the treatment of peripheral neuropathic pain. It exists in zwitterionic form in solid state. The present communication deals with the quantum chemical calculations of energies, geometrical structure and vibrational wavenumbers of GP using density functional (DFT/B3LYP) method with 6-311++G(d,p) basis set. In view of the fact that amino acids exist as zwitterions as well as in the neutral form depending on the environment (solvent, pH, etc.), molecular properties of both the zwitterionic and neutral form of GP have been analyzed. The fundamental vibrational wavenumbers as well as their intensities were calculated and compared with experimental FT-IR and FT-Raman spectra. The fundamental assignments were done on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanic...