Manishkumar R. Shimpi

Vibrational analysis and chemical activity of paracetamol-oxalic acid cocrystal based on monomer and dimer calculations : DFT and AIM approach

The study of structural and spectral characteristics of a paracetamol–oxalic acid (PRA–OXA) cocrystal has been carried out using two models (monomer and dimer), with the aim to understand the supramolecular structure and intramolecular interactions within the cocrystal. The cocrystal has been characterized by infrared and Raman spectroscopy combined with quantum chemical calculations molecular electrostatic potential surface (MEPS), frontier orbital analysis and electronic reactivity descriptors were used to understand the role of interactions involved in affecting the chemical reactivity of individual molecules in the cocrystal. It is observed that the CO, N–H and O–H groups of paracetamol are involved in hydrogen bonds to form cocrystals. NBO analysis suggests that the two types of interactions LP(1)(N8) → π*(C9–O10) and LP(2)(O10) → σ*(O25–H28) are responsible for the stability of the molecule. AIM analysis suggested that the non-covalent interactions are moderate in nature. The calculated HOMO–LUMO energies reveal that the charge transfer occurs within the cocrystal. Chemical reactivity parameters show that the cocrystal is more active than paracetamol.

New cocrystals of ezetimibe with L-proline and imidazole

The objectives of the study were to screen and prepare cocrystals of anti-cholesterol drug ezetimibe (EZT) with the aim of increasing its solubility and dissolution rate. Thermodynamic phase diagra ...

Atomistic Insight into Tetraalkylphosphonium Bis(oxalato)borate Ionic Liquid/Water Mixtures. 2. Volumetric and Dynamic Properties

Atomistic molecular dynamics simulations have been performed to investigate volumetric quantities and dynamic properties of binary trihexyltetradecylphosphonium bis(oxalato)borate ([P6,6,6,14][BOB]) ionic liquid (IL)/water mixtures with different water concentrations. The predicted liquid densities for typical [P6,6,6,14][BOB] IL/water mixtures are consistent with available experimental data with a relative discrepancy of less than 3%. The liquid densities and excess molar volumes of all studied [P6,6,6,14][BOB] IL/water mixtures are characterized by concave and convex features, respectively, within full water concentration range. The dynamic properties of [P6,6,6,14] cations, [BOB] anions, and water molecules are particularly analyzed through calculation of velocity autocorrelation functions, diffusion coefficients, and reorientational autocorrelation functions and correlation times. The translational and reorientational mobilities of three species become faster upon increasing water concentration in [P6,6,6,14][BOB] IL/water mixtures and present complex dynamical characteristics arising from three distinct microscopic diffusion features within the full water concentration range. The obtained striking volumetric quantities and particular dynamic properties are well correlated to microscopic liquid structural organization and distinct local ionic environment of all studied [P6,6,6,14][BOB] IL/water mixtures.

Relationship between mechanical properties and crystal structure in cocrystals and salt of paracetamol

Abstract Objectives were to study mechanical properties of various solid forms of paracetamol and relate to their crystal structures. Paracetamol form I (PRA), its cocrystals with oxalic acid (PRA-OXA) and 4,4-bipyridine (PRA-BPY) and hydrochloride salt (PRA-HCL) were selected. Cocrystals and salt were scaled-up using rational crystallization methods. The resulting materials were subjected to different solid-state characterizations. The powders were sieved and 90–360 µm sieve fraction was considered. These powders were examined by scanning electron microscopy (SEM) and densities were determined. Tablets were made at applied pressures of 35–180 MPa under controlled conditions and the tablet height, diameter and hardness were measured. Tensile strength and porosity of the tablets were estimated using well known models. Crystal structures of these systems were visualized and slip planes were identified. Cocrystal and salt of PRA were physically pure. Sieved powders had comparable morphologies and particle size. The apparent and theoretical densities of powders were similar, but no clear trends were observed. The tensile strengths of these compacts were increased with increasing pressure whereas tabletability decreased in the order oxalic acid > PRA-HCL ≈ PRA-OXA > BPY > PRA-BPY. Tablet tensile strength decreases exponentially with increasing porosity with the exception of PRY-BPY and BPY. Slip plane prediction based on attachment energies may not be independently considered. However, it was possible to explain the improved mechanical properties of powders based on the crystal structure. Cocrystallization and salt formation have introduced structural features that are responsible for improved tableting properties of PRA.

Studies of molecular structure, hydrogen bonding and chemical activity of a nitrofurantoin-L-proline cocrystal: a combined spectroscopic and quantum chemical approach

Nitrofurantoin (NTF) has been used as an antibacterial drug to treat bacterial infections of the urinary tract. The purpose of this work is to predict the hydrogen bonds (potential synthons) present in the cocrystal of nitrofurantoin-L-proline (NTF-LP) through a computational approach (DFT calculations) and validate using vibrational spectroscopic studies. The present study illustrates the formation and characterization of the cocrystal of NTF-LP. The molecular structure of the NTF-LP cocrystal has been predicted by forming several models on the basis of the hydrogen bonding patterns observed in other NTF cocrystals. A conformational study and potential energy surface scan have been plotted around three flexible bonds of the cocrystal molecule and two stable conformers have been obtained. NBO analysis of the second order perturbation theory of the Fock matrix suggests that interaction n1O(39) → σ*(N13–H21) is responsible for the stabilization of the molecule. Quantum theory of atoms in molecules (QTAIM) explains that all interactions are medium and partially covalent in nature as ∇2ρBCP > 0, HBCP < 0. The molecular electrostatic potential surface (MEPS) of the cocrystal has been visualized for its most electropositive potential in the region of the NH2+ group and most electronegative potential in the vicinity of the COO− group. The HOMO and LUMO energies and electronic charge transfer (ECT) confirms that charge flows from the co-former (LP) to NTF (API). Local reactivity descriptor parameters have been used to predict the reactive sites of the cocrystal and global reactivity descriptor parameters suggest that the cocrystal is softer thus more reactive in comparison to NTF. The experimental and theoretical results support the formation of the cocrystal through the strong hydrogen bond present between the NH group of NTF and carboxylate COO− group of LP and shows that LP is present in the zwitterionic form.

Understanding the thermal decomposition mechanism of a halogen-free chelated orthoborate-based ionic liquid: a combined computational and experimental study

In the last few decades, ionic liquids (ILs) have gained significant attention as lubricants and lubricant additives due to their polar nature, low vapour pressure and tunable physicochemical properties. In this work, quantum chemistry calculations and atomistic Molecular Dynamics (MD) simulations were employed to predict thermal degradation mechanisms of a potential lubricating agent - the tributyloctylphosphonium bis(oxalato)borate ([P4,4,4,8][BOB]) IL. It was found that the onset of decomposition of the studied IL coincides with a cleavage of the B-O bonds in the [BOB](-) anion. Consequently, a series of chemical reactions of the [P4,4,4,8](+) cation with the [BOB](-) anion was triggered yielding alkylboranes, alkenes, trialkylphosphines, CO and CO2. Another ionic system, consisting of [P4,4,4,8][Cl], was also tested for a comparison. Thermogravimetric measurements have shown a higher thermal stability of [P4,4,4,8][BOB] compared to that of [P4,4,4,8][Cl] at least at the initial stage of decomposition, in accord with the presented calculations. Quantum chemical frequency calculations also agreed with the experimental Fourier Transform Infrared (FTIR) spectroscopy results.

Molecular structure and hydrogen bond interactions of a paracetamol–4,4′-bipyridine cocrystal studied using a vibrational spectroscopic and quantum chemical approach

The purpose of the current study is to perform the structural and spectroscopic characterization of paracetamol-4,4′-bipyridine (PRA-BPY) cocrystal using infrared, Raman spectroscopy and density fu ...