@article { ISI:000313077100009, title = {Characterization of the structures and dynamics of phosphoric acid doped benzimidazole mixtures: a molecular dynamics study}, journal = {Journal of Molecular Modeling}, volume = {19}, number = {1}, year = {2013}, month = {JAN}, pages = {109-118}, publisher = {SPRINGER}, address = {233 SPRING ST, NEW YORK, NY 10013 USA}, abstract = {

Benzimidazole-based polymer membranes like poly(2,5-benzimidazole) (ABPBI) doped with phosphoric acid (PA) are electrolytes that exhibit high proton conductivity in fuel cells at elevated temperatures. The benzimidazole (BI) moiety is an important constituent of these membranes, so the present work was performed in order to achieve a molecular understanding of the BI-PA interactions in the presence of varying levels of the PA dopant, using classical molecular dynamics (MD) simulations. The various hydrogen-bonding interactions, as characterized based on structural properties and hydrogen-bond lifetime calculations, show that both BI and PA molecules exhibit dual proton-acceptor/donor functionality. An examination of diffusion coefficients showed that the diffusion of BI decreases with increasing PA uptake, whereas the diffusion of PA slightly increases. The hydrogen-bond lifetime calculations pointed to the existence of competitive hydrogen bonding between various sites in BI and PA.

}, keywords = {Diffusion coefficient, Hydrogen bond, molecular dynamics, Radial distribution functions}, issn = {1610-2940}, doi = {10.1007/s00894-012-1519-8}, author = {More, Minal and Pahari, Swagata and Roy, Sudip and Venkatnathan, Arun} } @article {48747, title = {Exploration of different solid variants of the anticancer medication Panobinostat (PNB) with improved physicochemical attributes}, journal = {Journal of Molecular Structure}, volume = {1292}, year = {2023}, month = {NOV }, pages = {136086}, type = {Article}, abstract = {

Panobinostat (PNB), is a medication used for the treatment of multiple myeloma. It is a BCS Class II drug with strong permeability and poor solubility. Therefore, it is highly desirable to investigate novel PNB variants with improved physiochemical properties. In this regard, several solid forms of PNB have been produced employing mechanochemistry and solution crystallisation techniques using a variety of GRAS (Generally Recognized as Safe) salt formers, notably oxalic acid (OA), fumaric acid (FA), maleic acid (MA), and succinic acid (SA). Powder X-Ray Diffraction (PXRD), Single Crystal X-Ray Diffraction (SCXRD), and thermal analysis such as Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC) were used to characterize all the synthesised molecular adducts. Hirshfeld surfaces and fingerprint plots demonstrate that the molecular entities are stabilized by O \& BULL;\& BULL;\& BULL;H, C \& BULL;\& BULL;\& BULL;H, C \& BULL;\& BULL;\& BULL;C and H \& BULL;\& BULL;\& BULL;H intermolecular interactions. Moreover, the solubility of parent PNB and its molecular adducts in pH 1.2/pH 6.8 was evaluated at room temperature. In every instance, an increase in the solubility of molecular salts relative to the parent medication is seen, notably PNB.MA exhibits enhanced solubility of 0.294 mg/ml, a 73fold increase over the parent PNB. Furthermore, it is observed that this upsurge in solubility of all the forms is static at pH 1.2. A thorough analysis of the recovered residue after solubility showed that most of the molecular adducts were stable at pH 6.8 and did not display any phase change or dissociation (with the exception of PNB.MA), but at pH 1.2 they transferred into a new stable form and extensive analysis confirmed that it converted into PNB.Cl salt. To the best of our knowledge, this is the first report on novel solid forms of PNB with enhanced physicochemical properties which implies that the obtained PNB molecular adduct may help in the development of improved PNB formulations.

}, keywords = {Hydrogen bond, Molecular adducts, solubility, Solvates}, issn = {0022-2860}, doi = {10.1016/j.molstruc.2023.136086}, author = {Kenguva, Gowtham and Giri, Lopamudra and Rout, Smruti Rekha and Acharya, Achyuta Nanda and Dandela, Rambabu} } @article {49383, title = {New binary adducts of panobinostat with different carboxylic acid based NSAIDs: structural analysis and physicochemical properties investigation}, journal = {ChemistrySelect}, volume = {9}, year = {2024}, month = {NOV}, pages = {e202403539}, type = {Article}, abstract = {

Adoption of multitarget, cost-effective fixed-dose medication combinations can help lower the pill load without increasing the risk of adverse events. In this study, three new 1:1 drug-drug binary solid forms of panobinostat (PNB) and nonsteroidal anti-inflammatory drugs (NSAIDs) were effectively synthesized by liquid-assisted grinding and slow evaporation crystallization techniques. The obtained solid forms were extensively characterized by various analytical techniques. The structural investigation revealed that all molecular adducts formed salt with a comparable R42\${\textbackslashmathrm{R}}_4\<\^\>2\$(10) graph set pattern created by heteromeric interactions formed between PNB and corresponding salt formers. To determine the dissolving behavior of the newly developed adducts, solubility tests were performed at various pH levels (pH 1.2 and pH 7), and the results indicated that the solubility of all forms is increased at pH 7.0, particularly PNB.NIF has a solubility of 0.195 mg/mL, which is seven times higher than the parent drug. Furthermore, PXRD was used to assess the stability of the synthesized adduct at varied temperature and humidity levels and it was found that all the adducts are stable. Based on the findings, we hope that the newly found PNB drug-drug binary adducts have possible potential to broaden the use of drug combinations without changing the chemical structures.

}, keywords = {Drug-drug salts, Heteromeric interactions, Hydrogen bond, Non-steroidal anti-inflammatory drugs, Panobinostat}, issn = {2365-6549}, doi = {10.1002/slct.202403539}, author = {Kenguva, Gowtham and Rout, Smruti Rekha and Kar, Ananya and Giri, Lopamudra and Shaikh, Tabrez R. and Jadab, Madhusmita and Pal, Satyanarayan and Dandela, Rambabu} } @article {49249, title = {Viscosity effects on the dynamics of diols and diol-based deep eutectic solvents}, journal = {Photochemistry and Photobiology}, volume = {100}, year = {2024}, month = {JUL}, pages = {946-955}, type = {Article}, abstract = {

Diols, characterized by the presence of two hydroxyl groups, form extended hydrogen-bonded networks. Increasing hydrocarbon chain length is known to elevate the viscosity of diols. Given the established influence of viscosity on solvent dynamics, it becomes imperative to comprehend the impact of viscosity on the fluctuation dynamics within diols and establish connections with hydrogen bond formation and breaking dynamics. In this study, we employ two-dimensional infrared spectroscopy to investigate the viscosity dependence of the structural evolution dynamics in three diols with varying chain lengths. Complementing our experimental approach, molecular dynamics simulations are conducted to extract hydrogen bond lifetimes. Our findings reveal a linear correlation between bulk viscosity, solvent fluctuation timescales, and hydrogen bond lifetimes. Notably, the selected diols exhibit the capability to form deep eutectic solvents upon mixing with choline chloride at specific molar ratios. In contrast to molecular solvents like diols, deep eutectic solvents are characterized by the formation of heterogeneous nanodomains, comprising various intercomponent hydrogen-bonded networks. Interestingly, our observations indicate that while the fluctuation dynamics decelerate with increasing bulk viscosity in diol-based deep eutectic solvents, the relationship between viscosity and dynamics is not linear, in contrast to the observed linearity in diols. This nuanced understanding contributes to the broader comprehension of the interplay between viscosity and dynamics in both molecular and deep eutectic solvents. We investigate the impact of viscosity on structural evolution dynamics in diols with varying chain lengths. Employing two-dimensional infrared spectroscopy and molecular dynamics simulations, we explore the relationship between bulk viscosity, solvent fluctuation timescales, and hydrogen bond lifetimes. We report a linear correlation in diols between viscosity, fluctuation timescales, and hydrogen bond lifetimes. Diols also form deep eutectic solvents, characterized by heterogeneous nanodomains. While fluctuation dynamics slow down with increasing bulk viscosity in diol-based deep eutectic solvents, the relationship between viscosity and dynamics is nonlinear, contrasting with diols{\textquoteright} linearity. This understanding enhances comprehension of viscosity-dynamics interplay in molecular and deep eutectic solvents.image

}, keywords = {Dynamics, Hydrogen bond, solvent, spectroscopy, viscosity}, issn = {0031-8655}, doi = {10.1111/php.13950}, author = {Chatterjee, Srijan and Deshmukh, Samadhan H. and Chowdhury, Tubai and Bagchi, Sayan} } @article {49517, title = {Synthesis, characterization and theoretical investigations of the newly developed molecular salts of an anti-psychotic drug (Penfluridol)}, journal = {Journal of Molecular Structure}, volume = {1328}, year = {2025}, month = {APR}, pages = {141392}, type = {Article}, abstract = {

Penfluridol (PEN) is a clinically relevant antipsychotic medication used to treat schizophrenia; nevertheless, its bioavailability is limited due to its poor solubility. To address this issues, new molecular salts of PEN are being produced utilizing an array of GRAS (Generally Recognised AS Safe) salt formers such as oxalic acid (OXA), malonic acid (MAL), maleic acid (MAE), and an artificial sweetener (saccharin (SAC)). A variety of solid-state analytical techniques were used to identify and characterize the resulting molecular salts. Moreover, PEN and its novel salts{\textquoteright} solubility were assessed using high-performance liquid chromatography (HPLC) and the data revealed that among all the adducts PEN.MAL exhibited a significantly higher solubility which is similar to 15 times more than the parent drug PEN. Furthermore, in order to enhance comprehension of the hydrogen bonding interaction, the Hirshfeld surface (HS), frontier molecular orbital (HOMO-LUMO), non-covalent interaction plots (NCIs), and electrostatic potential maps (ESP) investigations are discussed. Additionally, the stability of the synthesized adducts was evaluated over a 2-week period under accelerated humidity (90 \% +/- 5 \% RH, 40 +/- 1 degrees C) and it was observed that all the adducts demonstrated excellent stability. In light of the aforementioned observations, we expect that the latest discovery will be a superior alternative for refining and strengthening the pharmacological features of PEN.

}, keywords = {Anti-psychotic drug, Hydrogen bond, Liquid-assisted grinding (LAG), solubility}, issn = {0022-2860}, doi = {10.1016/j.molstruc.2025.141392}, author = {Kenguva, Gowtham and Rout, Smruti Rekha and Kar, Ananya and Giri, Lopamudra and Mahapatra, Sanat Kumar and Shaikh, Tabrez R. and Baidya, Debjani and Shelke, Nikita and Dandela, Rambabu} }