Journal of Physical Organic Chemistry最新文献

{"title":"Theoretical Study on the Prooxidant Activity of α- and β-Lapachones in Aqueous Media","authors":"Mario A. Vera-Guzmán,&nbsp;Ángel Trigos,&nbsp;Alberto V. Jerezano,&nbsp;Manuel E. Medina","doi":"10.1002/poc.70030","DOIUrl":"https://doi.org/10.1002/poc.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>The prooxidant activities of α- and β-lapachones were studied in aqueous media using density functional theory. Although these compounds are well-known prooxidants and have applications as alternatives in the treatment of tumor cells, little is known about the reaction mechanisms involved. The prooxidant activity of α- and β-lapachones considered their reduced forms; they are hydronaphthoquinones <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>H</mi>\u0000 <mn>2</mn>\u0000 </msub>\u0000 <msub>\u0000 <mi>Q</mi>\u0000 <mi>α</mi>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {mathrm{H}}_2{mathrm{Q}}_{alpha } $$</annotation>\u0000 </semantics></math> and <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <msub>\u0000 <mi>H</mi>\u0000 <mn>2</mn>\u0000 </msub>\u0000 <msub>\u0000 <mi>Q</mi>\u0000 <mi>β</mi>\u0000 </msub>\u0000 </mrow>\u0000 <annotation>$$ {mathrm{H}}_2{mathrm{Q}}_{beta } $$</annotation>\u0000 </semantics></math>, whereas the single electron transfer mechanism was considered in the reduction reaction where oxygen, hydrogen peroxide, copper, and iron were substrates. Two reaction routes were identified for the prooxidant activities of H₂Q_α and H₂Q_β: The first considered that the metals were not present in the reduction reactions of oxygen and hydrogen peroxide and obtained reaction rates of 10⁶–10⁷ M⁻¹ s⁻¹; the second considered that the metals copper and iron were present in the reduction reactions and the reaction rates were limited by diffusion. Understanding the reaction mechanism involved in the prooxidant activity of α- and β-lapachones and the physiological importance of these molecules could be employed to comprehend the anticancer properties of compounds in which prooxidant activity is involved.</p>\u0000 </div>","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 9","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Molecular Electron Density Theory Study for the Synthesis of Spirocyclic and Tricyclic Isoxazolines and Their Molecular Docking Evaluation for Antituberculosis Activity","authors":"Asmita Mondal,&nbsp;Luis R. Domingo,&nbsp;Haydar A. Mohammad-Salim,&nbsp;Nivedita Acharjee","doi":"10.1002/poc.70028","DOIUrl":"https://doi.org/10.1002/poc.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>The [3 + 2] cycloaddition (32CA) reactions of aryl and heteroaryl nitrile oxides with (S)-(−)-β-pinene and (R)-(+)-α-pinene have been theoretically studied from the Molecular Electron Density Theory (MEDT) perspective and a molecular docking evaluation for the antituberculosis activity of the isoxazoline products. The studied 32CA reactions show activation Gibbs free energies between 23.8 and 31.6 kcal·mol⁻¹, consistent with their zwitterionic character and exclusive regioselectivity, in complete agreement with the experiments. <i>Two-stage one-step</i> mechanism with a very low polar character is predicted. The molecular mechanism has been established from the Bonding Evolution Theory (BET) analysis along the reaction path, showing early transition state structures, with weak non-covalent interactions indicated from the quantum theory of atom-in-molecules (QTAIM) analysis. The isoxazoline products for the 32CA reactions of (S)-(−)-β-pinene show appreciable binding affinities towards <i>Mycobacterium tuberculosis</i> transcriptional repressor EthR2, revealing them as promising candidates with antituberculosis potential.</p>\u0000 </div>","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiradical Potency of Diphlorethol: DFT (Density Functional Theory), Molecular Docking, and ADMET Profile","authors":"Chu Anh Van,&nbsp;Tran Quang Hai,&nbsp;Nguyen Xuan Ha,&nbsp;Nguyen Thi Hanh,&nbsp;Nguyen Ngoc Linh,&nbsp;Ninh The Son","doi":"10.1002/poc.70029","DOIUrl":"https://doi.org/10.1002/poc.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>Diphlorethol is a typical phlorotannin with multipharmacological activities. However, its antiradical activity is still ambiguous. The current study aims to evaluate its radical scavenging using thermodynamics and kinetics-based density functional theory (DFT) calculations. The results indicated that the main radical scavenging mechanism in gas and lipid was the formal hydrogen transfer (FHT), and that for the aqueous medium was the sequential proton loss-electron transfer (SPLET). The kinetic reactions with HOO˙ and CH₃OO˙ radicals resulted in the <i>k</i>_overall (overall rate constant) of 1.2 × 10⁸–1.6 × 10⁸ M⁻¹ s⁻¹ in water and 3.0 × 10⁰–2.7 × 10¹ M⁻¹ s⁻¹ in pentyl ethanoate. 4- and 6-OH acted as active centers for radical scavenging. The molecular docking simulation suggested that diphlorethol could serve as a potential inhibitor of the oxidative activity of the Keap1 enzyme, particularly through its interaction with the crucial amino acid residue Arg415. The ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis demonstrated that diphlorethol exhibited favorable pharmacokinetic properties, including good water solubility, high intestinal absorption, and moderate tissue distribution. Diphlorethol did not induce hepatotoxicity or skin sensitization and showed no inhibitory effects on hERG I or hERG II channels, supporting its potential as a safe antioxidant candidate for further development.</p>\u0000 </div>","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetics of Double-Bond Isomerizations Among 1-Octene and cis and trans Linear Internal Octenes on Dry Amberlyst15 Catalyst: Adsorbed Alcohol Becomes an Active Site","authors":"Jeffrey C. Gee,&nbsp;Karen W. Fulbright,&nbsp;Daniel H. Ess,&nbsp;Jyothish Joy","doi":"10.1002/poc.70026","DOIUrl":"https://doi.org/10.1002/poc.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>The double-bond isomerization of 1-octene to an equilibrium distribution of all seven linear octene isomers on a dry Amberlyst15 catalyst was followed at 90°C using gas chromatography to resolve five of the seven isomers. The simplest kinetic models that fit observed data over several hours indicated that carbenium ions are likely intermediates in these isomerizations. The C2 octyl carbenium ion appeared to be more stable than the C3 and C4 octyl carbenium ions, leading to a lower equilibrium <i>trans</i> to <i>cis</i> ratio in 2-octene than in 3-octenes and 4-octenes. At equilibrium, [2-octyl carbenium ion] / [3-octyl carbenium ion] = 1.6. The octene adsorption coefficient for double-bond isomerization on this catalyst was 0.4–0.5, indicating a rather weak adsorption. However, the concurrent dimerization of octene to branched hexadecene isomers required an adsorption coefficient of ~40, indicating octene adsorbs onto two different types of sites on this catalyst. The primary alcohol 2-ethyl-1-hexanol was added to reaction mixtures to suppress octene dimerization, and the active isomerization site in this work was a molecule of 2-ethyl-1-hexanol adsorbed onto a supported sulfonic acid group of the initial resin. This new site was less active than the original acid site.</p>\u0000 </div>","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Structure of Dicyclopentadiene by Gas-Phase Electron Diffraction and Theoretical Calculations","authors":"Valeriya A. Mukhina,&nbsp;Alexey V. Eroshin,&nbsp;Ilya S. Navarkin,&nbsp;Sergey A. Shlykov","doi":"10.1002/poc.70027","DOIUrl":"https://doi.org/10.1002/poc.70027","url":null,"abstract":"<div>\u0000 \u0000 <p>In this article, the structure of the free dicyclopentadiene (DCPD) molecule was studied for the first time by the gas-phase electron diffraction (GED) at 268 K supplemented by quantum chemical calculations (B3LYP and MP2 with the cc-pVTZ basis set). The possibility of transition between endo and exo isomers of DCPD was considered in the gas phase. Three models of the refinement of the experimental (GED) data were applied on the base of two harmonic force fields and molecular dynamic simulations. The theoretical and experimental geometric parameters of the endo isomer are presented. In addition, the geometric parameters of the exo isomer calculated by quantum chemistry are given.</p>\u0000 </div>","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Density Functional Theory Study of the Reductive Removal of Epoxide Oxygen From Small Polycyclic Aromatic Hydrocarbon Surface","authors":"Hiroshi Kawabata,&nbsp;Hiroto Tachikawa,&nbsp;Masahiro Shinoda","doi":"10.1002/poc.70022","DOIUrl":"https://doi.org/10.1002/poc.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>The conductivity of graphene oxide is significantly increases when it is reduced, and oxygen is removed. In this study, the mechanism of deoxygenation of the epoxide sites of small polycyclic aromatic hydrocarbons (PAHs) with triphenylphosphine (PPh₃) was investigated using DFT. When PPh₃ attacks the epoxide oxygen, the carbon–oxygen bond is immediately cleaved by electron transfer, and the oxygen is then abstracted to form triphenylphosphine oxide. The reaction was found to be single-step and different from that of three-membered ring ethers, which are not bound to PAHs. The activation energy for deoxygenation is approximately 20 kcal/mol, and the reaction is exothermic.</p>\u0000 </div>","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Aromaticity of Fluorinated Benzene Derivatives Using New Descriptors Based on the Distributed Multipole Analysis (DMA) Partition of the Electron Density","authors":"Nathália M. P. Rosa,&nbsp;Matheus Máximo-Canadas,&nbsp;Itamar Borges Jr","doi":"10.1002/poc.70024","DOIUrl":"https://doi.org/10.1002/poc.70024","url":null,"abstract":"&lt;p&gt;We investigated the impact of fluorination on the aromaticity of 12 benzene-based compounds using a recently proposed new set of six descriptors (ACS Omega 2025, 10, 14, 14157–1417) based on the distributed multipole analysis (DMA) partition of the electron density. These descriptors allow the quantification of electron delocalization, an observable property related to aromaticity, and were defined from the components of the DMA quadrupole moment tensor &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;Q&lt;/mi&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {boldsymbol{Q}}_2 $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;, the first electric multipole moment with out-of-plane contributions. We found a decrease in aromaticity that is related to the electron-withdrawing inductive effects of fluorine substituents, which modify the electron density distribution on the ring, particularly in regions adjacent to the substituents. The analysis by the &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;Q&lt;/mi&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {boldsymbol{Q}}_2 $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;-based aromaticity descriptors revealed a strong correlation between electron distribution and electronic delocalization in fluorinated systems, confirming that fluorine substituents directly affect the symmetry and uniformity of electronic delocalization. A linear relationship between the &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;Q&lt;/mi&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {boldsymbol{Q}}_{mathbf{2}} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; descriptors &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;Q&lt;/mi&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;mi&gt;zz&lt;/mi&gt;\u0000 &lt;mo&gt;,&lt;/mo&gt;\u0000 &lt;mtext&gt;origin&lt;/mtext&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ {Q}_{2 zz, origin} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; and the &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mtext&gt;NICS&lt;/mtext&gt;\u0000 &lt;mfenced&gt;\u0000 &lt;mn&gt;1&lt;/mn&gt;\u0000 &lt;/mfenced&gt;\u0000 &lt;mi&gt;zz&lt;/mi&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ NICS(1) zz $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; and ring current strength ","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/poc.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functionalization of Graphene Flake Surfaces With p-Substituted Phenyl Radicals: Estimation of Activation Energies From Hammett Substituent Constants","authors":"Hiroshi Kawabata,&nbsp;Hiroto Tachikawa,&nbsp;Masahiro Shinoda","doi":"10.1002/poc.70025","DOIUrl":"https://doi.org/10.1002/poc.70025","url":null,"abstract":"<div>\u0000 \u0000 <p>Chemical modification of flat graphene surfaces composed of pure sp² carbons is extremely challenging. In this study, we used density functional theory to investigate the addition of phenyl radical derivatives to the surface of graphene flakes and clarified the effect of the nature of the substituents on the activation energy using Hammett plots. Circumcoronene was used as a model for the graphene flakes, and 13 <i>para</i>-substituted phenyl radicals were used as radical species. The activation energy consists of the distortion energies of the graphene flakes and radical species and the interaction energy between the graphene flakes and radical species. The interaction energy is 30%–40% of the activation energy. The interaction energy between the nitrophenyl radical and graphene flake is 3.1 kcal/mol, 2.3 kcal/mol lesser than that between the <i>N,N</i>-dimethylamino-phenyl radical and graphene flake. As the electron-withdrawing properties of the substituents increase, the interaction energy decreases, and consequently, the activation energy decreases. Furthermore, natural energy decomposition analysis shows that the intermolecular interactions are stabilized by charge transfer and electrostatic interactions, the magnitudes of which increase when increasing the Hammett constants of the substituents.</p>\u0000 </div>","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reaction of N-Allenyl-1H-Pyrrole-2-Yl-Carbaldehydes With Hydroxylamine: A Quantum Chemical Insight Into the Mechanism and Substituent Influence","authors":"Alexander S. Bobkov,&nbsp;Nikita V. Teplyashin,&nbsp;Svetlana V. Martynovskaya,&nbsp;Andrey V. Ivanov,&nbsp;Nadezhda M. Vitkovskaya","doi":"10.1002/poc.70023","DOIUrl":"https://doi.org/10.1002/poc.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>We report on a quantum chemical study (B2PLYP-D3BJ/6-311+G**//B3LYP/6-31+G*) of the mechanism of the reaction of <i>N</i>-allenyl-1<i>H</i>-pyrrole-2-yl-carbaldehydes with hydroxylamine in ethanol leading to pyrrolopyrazine oxides. The main focus is placed on unraveling the influence of the nature of the substituent in the fourth and fifth positions of the pyrrole ring on the kinetic characteristics of the key stages of the reaction, which are oximation and intramolecular cyclization. The aryl substituents are found to favor the reaction, in contrast to the alkyl substituents.</p>\u0000 </div>","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Fundamental Origin of the Polar Contribution to Heat Capacity Changes in Hydration in an Aqueous Solution","authors":"Maxim P. Evstigneev,&nbsp;Anastasiya O. Lantushenko","doi":"10.1002/poc.70021","DOIUrl":"https://doi.org/10.1002/poc.70021","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;p&gt;The current understanding of the nature of the physical factors making up the experimentally measured heat capacity change (&lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;∆&lt;/mo&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;C&lt;/mi&gt;\u0000 &lt;mi&gt;P&lt;/mi&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ Delta {C}_P $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;) for hydration/solvation occurring with net-neutral solutes at equilibrium in an aqueous solution is based on a large body of experimental work done from 1970 to 2000 which postulates the leading role of the hydrophobic effect (HE) in &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;∆&lt;/mo&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;C&lt;/mi&gt;\u0000 &lt;mi&gt;P&lt;/mi&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ Delta {C}_P $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt;. Other contributions have also been identified, but their relative role and nature are not well understood. In the present work, we provide a new insight into the nature of the fundamental terms contributing to &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;∆&lt;/mo&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;C&lt;/mi&gt;\u0000 &lt;mi&gt;P&lt;/mi&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ Delta {C}_P $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; for a wide variety of molecular processes in an aqueous solution. The crux of our findings is the identification of two leading physical factors, viz., the long known HE and the newly found non-specific solute-solvent van der Waals orientational interactions (Keesom force), making up the magnitude of experimental &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;∆&lt;/mo&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;C&lt;/mi&gt;\u0000 &lt;mi&gt;P&lt;/mi&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ Delta {C}_P $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; in a general case under the standard conditions of an aqueous solution, “classical” manifestation of HE and employing the model of a rigid net-neutral solute. As a consequence, one can now characterize the thermodynamic nature of various molecular interactions in a solution based on the level of &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;∆&lt;/mo&gt;\u0000 &lt;msub&gt;\u0000 &lt;mi&gt;C&lt;/mi&gt;\u0000 &lt;mi&gt;P&lt;/mi&gt;\u0000 &lt;/msub&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ Delta {C}_P $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; from a single viewpoint, including the identification of the leading factor, understanding the interrelation of different factors, the interpretation of the sign of &lt;span","PeriodicalId":16829,"journal":{"name":"Journal of Physical Organic Chemistry","volume":"38 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}