{"title":"Mechanism of Drug Potency Enhancement via Methylation","authors":"Goga Ram, Nirmalya Bachhar","doi":"10.1039/d5cp03050a","DOIUrl":"https://doi.org/10.1039/d5cp03050a","url":null,"abstract":"In the past decade, the effect of methyl groups on drug molecules has gained raising interest in medicinal chemistry. Recent research has shown that the methyl group enhances the pharmaceutical potency and specificity of drugs, a phenomenon commonly referred to as the \"magic methyl effect\". A site-selective introduction of methyl group(s) in drug molecules can often modify several pharmaceutical properties, including drug potency, biological activity, pharmacodynamics, and pharmacokinetics. The current literature qualitatively suggests that this potency enhancement via targeted methylation is the effect of alteration of physical parameters like drug solubility, hydrophobicity, and conformational change. However, a quantitative thermodynamic framework that can be used as a design tool to enhance the drug potency using these parameters is missing. We aim to understand this effect from a thermodynamic standpoint by taking drug molecules and proteins. An all-atom molecular dynamics simulation and molecular docking were performed to obtain thermodynamic parameters, including binding free energy, polarity, and conformational change. We developed a correlation to quantify the polarity of protein cavities based on the hydropathy index. Our analysis shows that conformational changes resulting from methylation are a key factor influencing drug potency in both hydrophilic and hydrophobic protein cavities. Additionally, the methyl effect is position-specific, and we defined how to quantify an optimum position for methylation that leads to higher enhancement. Finally, this study guides how one can add a methyl group to the drug molecule that can enhance potency, which has implications for healthcare and pharmaceuticals.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"68 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Partial Atomic Charge of Oxygen and Hydrogen Bonding Ability: Insights from Mass-Selective IR Spectroscopy of Jet-Cooled Hydrogen-Bonded Complexes","authors":"Akshay Kumar Sahu, Anant Ram Satpathi, Saiprakash Rout, Radharaman Samanta, Laxmipriya Dash, Himansu S. Biswal","doi":"10.1039/d5cp03250d","DOIUrl":"https://doi.org/10.1039/d5cp03250d","url":null,"abstract":"Hydrogen bond is a fundamental non-covalent interaction that underpins the structure and function of chemical and biological systems. While the nature of conventional hydrogen bonding is predominantly electrostatic, accurately describing the atomic charge distribution within molecules remains a significant challenge, as atomic charges are not physically observable quantities. In this work, we present a systematic experimental investigation of hydrogen bonding in the gas phase using mass-selective IR spectroscopy of jet-cooled p-cresol–acceptor dimers. The redshift of the p-cresol OH stretching frequency (ΔνOH) serves as a direct measure of hydrogen-bond strength. We analysed two series of acceptors, acyclic alcohols and ethers, which demonstrate increasing inductive effects, and cyclic ethers, which reveal the influence of resonance. The gas-phase spectroscopy results provide a dataset that serves as a benchmark for validating computational chemistry models used for atomic charge calculation. It was demonstrated that while standard hydrogen-bonding descriptors correlate well with the experimental data, many popular partial atomic charge models fail to reproduce the observed chemical trends. This failure could be due to the over-reliance of the models on the electronegativity of directly bonded atoms. By highlighting this discrepancy, this work serves as a valuable cautionary to use atomic charge and underscores the need for better theoretical frameworks for atomic charge estimation.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"101 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design of orthogonally jointed 2D transition metal dichalcogenide heterojunctions for enhanced Photoelectrochemical water reduction","authors":"Chih-hung Wu, Keng-Hung Chang, Yu-Hao Tu, Heng-Jui Liu, Chen-Hao Yeh","doi":"10.1039/d5cp02368h","DOIUrl":"https://doi.org/10.1039/d5cp02368h","url":null,"abstract":"2D transition metal dichalcogenide (TMD) heterostructures are promising photoelectrode materials for photoelectrocatalysis due to their favorable band structures and chemical activity. Unlike conventional layered-stacked designs, this study explores orthogonally jointed WS<small><sub>2</sub></small>/MoS<small><sub>2</sub></small> and MoS<small><sub>2</sub></small>/WS<small><sub>2</sub></small> heterostructures grown on p-Si via RF magnetron sputtering by controlling TMD thickness. The orthogonal-connecting configuration exposes abundant edge sites, enhancing catalytic activity. Both heterostructures outperform individual MoS<small><sub>2</sub></small> and WS<small><sub>2</sub></small> in photoelectrochemical (PEC) water splitting, with WS<small><sub>2</sub></small>/MoS<small><sub>2</sub></small> achieving the highest photocurrent density. Band alignment analysis shows a staggered energy configuration in WS<small><sub>2</sub></small>/MoS<small><sub>2</sub></small>/p-Si, promoting efficient charge separation. Additionally, theoretical calculations reveal that orthogonally jointed heterojunction has negative hydrogen adsorption energies, unlike their layered counterparts, which improves hydrogen evolution reaction (HER) kinetics. This work highlights a previously unexplored TMD-based heterostructure with enhanced solar water-splitting performance.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"39 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thermodynamic properties of water in aqueous amine solutions studied by energy-representation method","authors":"Yuki Yokoyama, Keiji Yasuda, Tsuyoshi Yamaguchi","doi":"10.1039/d5cp02422f","DOIUrl":"https://doi.org/10.1039/d5cp02422f","url":null,"abstract":"The use of aqueous amine solutions for CO₂ capture is considered as a promising strategy for mitigating global warming, and reducing the energy consumption of the capture process is essential for its widespread adoption. Understanding the mechanisms that govern the vapor pressure of water and enthalpy of water vaporization of CO2-loaded solutions can contribute to lowering the energy cost of CO2 capture. In this study, molecular dynamics simulations of aqueous amine solutions before and after CO2 absorption were performed, and the solvation free energy of water was evaluated using the energy representation method. The results revealed that vapor pressure decreases by CO2 absorption, particularly due to the formation of anions that strongly interact with water through hydrogen bonding. The contributions of each solvent species to the solvation free energy and solvation energy were also quantified. It was found that the enthalpy of vaporization increases with amine concentration both before and after CO2 absorption. Before CO2 absorption, this increase is attributed to enhanced energetic interactions, despite the destabilization in solvation free energy due to entropic contributions. Additionally, snapshots indicated water localization in certain systems. Analysis of concentration fluctuations showed that concentration regions with greater fluctuations tended to exhibit smaller changes in vapor pressure with respect to concentration, suggesting a correlation between microscopic structure formation and macroscopic thermodynamic properties.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"105 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Magnesium Perfluorinated Pinacolatoborate in Diglyme: Understanding Microscopic Structure in Rechargeable Magnesium Batteries","authors":"Nadezhda A. Andreeva, Vitaly V. Chaban","doi":"10.1039/d5cp02632f","DOIUrl":"https://doi.org/10.1039/d5cp02632f","url":null,"abstract":"Magnesium-ion batteries represent a hot research topic, thanks to their arguable potential for rechargeable portable devices. Unlike lithium, magnesium is the eighth most abundant element in the Earth’s crust, exhibiting physicochemical merits as an anode material. Thermodynamically and electrochemically stable electrolyte solutions must work in conjunction with Mg-ion batteries. We report a computational investigation of the recently synthesized chloride-free electrolyte, magnesium fluorinated pinacolatoborate [Mg][PFB]2 in diglyme (DGM). [Mg][PFB]2 exhibits a fascinating electrochemical performance, making it suitable for high-voltage Mg-ion batteries. By determining a representative manifold of low-energy stationary points in the [Mg][PFB]2 and [Mg][PFB]2 + DGM electrolyte compositions, we characterized non-covalent features and solvation shells, partial charge distributions, electrostatic potentials, electron transfers, solvation thermodynamics, nucleophilic and electrophilic binding centers, and other relevant properties. We found that DGM and FBP competed for the most thermodynamically favorable solvation of the Mg-ion. DGM readily penetrated the ion [Mg][PFB]2 triplet and formed a few Mg…O ionic bonds. Competitive Mg…FPB and Mg…DGM bindings foster the mobility of a charge carrier in the electrolyte. The newly reported findings rationalize previous experimental observations and provide new predictions. They are addressed to electrochemists developing magnesium metal batteries.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"24 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electric field-induced circularly polarised luminescence switching in chiral nematic liquid crystal with negative dielectric anisotropy","authors":"Daiya Suzuki, Kosuke Kaneko, Yoshitane Imai","doi":"10.1039/d5cp03335g","DOIUrl":"https://doi.org/10.1039/d5cp03335g","url":null,"abstract":"An emissive chiral nematic liquid crystal (N*-LC-MBBA/CPDI) was fabricated by doping an achiral nematic liquid crystal (N-LC), namely N-(4-methoxybenzylidene)-4-butylaniline (MBBA), which exhibits a negative dielectric anisotropy (Δε < 0), with the chiral luminophore N,Nʹ-bis(1-cyclohexylethyl)perylene-3,4,9,10tetracarboxylic diimide (CPDI). In contrast to the previously reported emissive chiral N-LC (N*-LC-6CB/CPDI) composed of a positive dielectric anisotropy N-LC, N*-LC-MBBA/CPDI exhibited no circularly polarised luminescence (CPL) in the absence of a direct current (DC) electric field. However, upon the application of a DC electric field, a pronounced CPL signal emerged due to helical axis reorientation in the chiral nematic host. Under the optimised conditions, the system displayed a high dissymmetry factor with |g<small><sub>CPL</sub></small>| values reaching up to 0.36. Moreover, the CPL response was reversible and continuously switchable upon electric field modulation. Overall, this study presents an effective strategy for the development of functional CPL-switching devices based on the DC field-driven control of N*-LCs.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"61 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vassilis Gkatsis, Petros Maratos, Christoforos Rekatsinas, George Giannakopoulos, Panagiotis Krokidas
{"title":"Density-Aware Active Learning for Materials Discovery: A Case Study on Functionalized Nanoporous Materials","authors":"Vassilis Gkatsis, Petros Maratos, Christoforos Rekatsinas, George Giannakopoulos, Panagiotis Krokidas","doi":"10.1039/d5cp02908b","DOIUrl":"https://doi.org/10.1039/d5cp02908b","url":null,"abstract":"Machine learning algorithms often rely on large training datasets to achieve high performance. However, in domains like chemistry and materials science, acquiring such data is an expensive and laborious process, involving highly trained human experts and material costs. Therefore, it is crucial to develop strategies that minimize the size of training sets while preserving predictive accuracy. The objective is to select an optimal subset of data points from a larger pool of possible samples, one that is sufficiently informative to train an effective machine learning model. Active Learning (AL) methods, which iteratively annotate data points by querying an oracle (e.g., a scientist conducting experiments), have proven highly effective for such tasks. However, challenges remain, particularly for regression tasks, which are generally considered more complex in the AL framework. This complexity stems from the need for uncertainty estimation and the continuous nature of the output space. In this work, we introduce Density-Aware Greedy Sampling (DAGS), an active learning method for regression that integrates uncertainty estimation with data density, specifically designed for large design spaces (DS). We evaluate DAGS on both synthetic data and multiple real-world datasets of functionalized nanoporous materials, such as metal-organic-frameworks (MOFs) and covalent-organic-frameworks (COFs), for separation applications. Our results demonstrate that DAGS consistently outperforms both random sampling and state-of-the-art AL techniques in training regression models effectively with a limited number of data points, even in datasets with a high number of features.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"97 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aikaterini Tsirkou, Nina Tymínska, Richard O'Hair, Fabien Grasset, Yann Molard, Karine Costuas, Stéphane Cordier, Luke MacAleese
{"title":"Gas-phase reactivity of hexanuclear molybdenum [Mo6I14]2- and its photo-fragments towards O2 and CO2: combined mass spectrometry (MSn) and quantum chemical simulations","authors":"Aikaterini Tsirkou, Nina Tymínska, Richard O'Hair, Fabien Grasset, Yann Molard, Karine Costuas, Stéphane Cordier, Luke MacAleese","doi":"10.1039/d5cp02611c","DOIUrl":"https://doi.org/10.1039/d5cp02611c","url":null,"abstract":"The optical properties, photo-decomposition and photo-reactivity of [Mo<small><sub>6</sub></small>I<small><sub>14</sub></small>]<small><sup>2-</sup></small> clusters and associated photo-products are examined in the gas phase. The UV-visible optical spectrum of the electron-rich [Mo<small><sub>6</sub></small>I<small><sub>14</sub></small>]<small><sup>2-</sup></small> cluster is measured and the wavelength dependence of the principal fragments is interpreted on the basis of the quantum chemistry (QC) simulated spectrum and detailed transitions. A special focus is made on the photo-generated [Mo<small><sub>6</sub></small>I<small><sub>14</sub></small>]<small><sup>1-</sup></small> and photo-specific radical [Mo<small><sub>6</sub></small>I<small><sub>13</sub></small>]<small><sup>2-•</sup></small> as well as on halogen-depleted clusters [Mo<small><sub>6</sub></small>I<small><sub>n</sub></small>]<small><sup>1-</sup></small> with n<14. The fragmentation and reaction energetics of all species are examined with a combination of mass spectrometry experiments, ion-molecule reactions with O<small><sub>2</sub></small> and CO<small><sub>2</sub></small> under irradiation and QC simulations. Reactions with O<small><sub>2</sub></small> are shown to be very exergonic with up to 5 eV release when O<small><sub>2</sub></small> is dissociated on the cluster. Experimental evidences for the photo-decomposition of CO<small><sub>2</sub></small> into CO and O on [Mo<small><sub>6</sub></small>I<small><sub>n</sub></small>]<small><sup>1-</sup></small> ions are provided together with detailed QC energetics.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"4 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insights into Polarized Raman, Infrared, and Dielectric Spectra of Lead-Free (Na0.5Bi0.5)ZrO3 : A Density Functional Theoretical Investigation","authors":"Manish Saha, Saket Asthana, Manish Niranjan","doi":"10.1039/d5cp01885d","DOIUrl":"https://doi.org/10.1039/d5cp01885d","url":null,"abstract":"In this work, we present a DFT based first principle theoretical investigation of lattice dynamics, electronic structure, and dielectric properties of room temperature phase of Na0.5Bi0.5ZrO3 (NBZ) system. In particular, theoretical and experimental Raman studies of the system are performed and the symmetry labels of NBZ vibrational modes are assigned. In addition, theoretical polarized Raman spectra, Born-effective charge tensors, Infrared (IR) reflectivity, oscillator strengths etc. are obtained and analysed. The experimental bandgap energy is obtained using UV–Vis spectroscopy. Experimental Raman spectra at room temperature are recorded. The experimental and computed Raman spectrum shows good agreement with each other. The Raman mode intensities are computed for different light polarization configurations suggest the presence of different symmetry modes for each polarization setup. The electronic band structure and density of states of NBZ are investigated, and optical absorption spectrum is also determined. Moreover, we explored the effectiveness of DFT semi-local, hybrid and meta-GGA exchange-correlations (XC) functionals as well as the impact of spin-orbit coupling (SOC), on electronic band gap estimations. The electron localization function, COHPs and Bader charge analysis are also carried out to determine the bonding nature in the NBZ compound. In summary, our work presents important benchmark insights on NBZ, that were not reported before.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"78 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Bulk Photovoltaic Effect in the One-Dimensional Interface of Graphene/BN Superlattice","authors":"Yue Gao, Wenli Zou, Chunmei Zhang","doi":"10.1039/d5cp03159a","DOIUrl":"https://doi.org/10.1039/d5cp03159a","url":null,"abstract":"Heterointerfaces serve as critical platforms for tailoring bulk photovoltaic effect (BPVE), especially the one-dimensional (1D) interface, which often offers high densities of states, thus resulting in superior optical responses. However, the role of the 1D interface in modulating the BPVE remains largely underexplored. Here, we investigate BPVE in a 1D interface formed by graphene and boron nitride building blocks (graphene/BN) along the armchair direction. The system reduces to C2v symmetry and allows for the shift current flowing along the interface of graphene/BN. The BPVE can be tailored by varying the width of the graphene/BN superlattice. Specifically, the shift current exhibits a 3-periodic enhancement with increasing width (N=1-6). This behavior stems from Brillouin zone folding mediated interband coupling between primary and secondary band extrema. Furthermore, the carbon stoichiometry of graphene/BN enables a redshift of the shift current, effectively activating the absorption of low-energy light. Our work establishes a novel paradigm for 1D interface engineering of the BPVE.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"1 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}