The Journal of Physical Chemistry B最新文献

{"title":"","authors":"Andreas Steinhoff, Alexandra Höltzel and Ulrich Tallarek*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 25","pages":"XXX-XXX 2305–2315"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.5c01697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Energy Pathway of Lipid Monolayer Fusion: From Droplet Contact to Coalescence.","authors":"Rodion J Molotkovsky, Timur R Galimzyanov, Mariya M Minkevich, Konstantin V Pinigin, Peter I Kuzmin, Pavel V Bashkirov","doi":"10.1021/acs.jpcb.5c02054","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c02054","url":null,"abstract":"<p><p>Neutral fats in living organisms are stored in lipid droplets, intracellular organelles enveloped by a phospholipid monolayer. The fusion of these lipid droplets is vital for numerous physiological functions and is regulated by specific proteins and lipids. Dysregulation of this process, leading to excessive droplet growth, is associated with various pathological conditions. Notably, changes in the lipid composition of the boundary monolayers can significantly influence the fusion rate, mirroring fusion dynamics of membranous compartments surrounded by lipid bilayers. In this study, we conducted a theoretical and computational analysis of monolayer fusion, extending the established bilayer fusion model to this context. We characterize the energy trajectory associated with monolayer fusion, tracing the process from the initial unperturbed state to the formation of physical contact between monolayers, and subsequently to the expansion of this structure, which we refer to as the monolayer stalk, analogous to bilayer fusion. Unlike bilayer fusion, monolayer fusion features a single energy barrier, determining the process efficiency. Once this barrier is overcome, further droplet merging occurs spontaneously, highlighting the dynamic nature of lipid droplet interactions. We analyze how lipid composition influences this energy barrier and explore the effects of factors such as Gaussian curvature and hydration-induced repulsion on the energy landscape. Our calculations reveal that Gaussian curvature energy significantly contributes to barrier height. An increase in the proportion of lipids exhibiting large negative spontaneous curvature, which enhances fusion likelihood, can substantially decrease this barrier. Our findings are consistent with existing experimental data and allow us to quantify the barrier height as a function of lipid composition. Specifically, we demonstrate that incorporating 50 mol % of dioleoylphosphatidylethanolamine (DOPE) into pure dioleoylphosphatidylcholine (DOPC) monolayers reduces the energy barrier height by approximately 16 <i>k</i>_B<i>T</i> - half of this reduction attributed to changes in spontaneous curvature, with the other half due to modification in hydration repulsion parameters. These findings provide quantitative insights into lipid droplet fusion mechanisms, advancing our understanding of lipid metabolism and its physiological regulation.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Yi Zheng,&nbsp;Rongrong Shen,&nbsp;Yunuo Dai,&nbsp;Yile Xie,&nbsp;Chaojie Wang,&nbsp;Yuepiao Cai* and Kun Wang*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 25","pages":"XXX-XXX 2305–2315"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.5c01232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Andreas Steinhoff,&nbsp;Alexandra Höltzel and Ulrich Tallarek*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":"129 25","pages":"XXX-XXX 2305–2315"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.5c01695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144479745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Range Water Ordering between Intrinsically Disordered Proteins and Its Impact on Protein Diffusion.","authors":"Hongli Li, Binming Han, Moxin Zhang, Guorong Hu, Jingyuan Li","doi":"10.1021/acs.jpcb.5c01831","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c01831","url":null,"abstract":"<p><p>Intrinsically disordered proteins (IDPs) play a critical role in the formation of membraneless organelles. The reduced diffusion of IDPs is associated with the stability of condensates and the related biological processes including phase separation and molecular recognition. Here we employ molecular dynamics simulations to investigate the diffusion dynamics of the LAF-1 RGG domains as well as their interplay with the solvent environment. Our results show that the structural ordering of water molecules between IDPs is significantly enhanced, even when the IDPs are well separated. The extensive structural ordering is accompanied by the slowdown in the diffusion dynamics of substantial water between IDPs. These effects of the IDPs on water molecules can be attributed to the high enrichment of charged residues in disordered conformations, which could form strong hydrogen bonds with hydration water and facilitate the formation of the hydrogen bond network of substantial water between these IDPs. In fact, the increase in the proportion of water ordering between IDPs and the slowing down of the water diffusion imply an effect equivalent to an 18 K cooling of the solvent environment between the IDPs. The effective viscosity for IDPs is thus considerably increased and slows their diffusion even when there are no interchain contacts between IDPs.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Permeation Enhancers on Transcellular Permeation of Small Molecule Drugs.","authors":"Mabel Bernaldez, Christopher Kang, Stephen D Stamatis, John P Rose, Rui Sun","doi":"10.1021/acs.jpcb.5c00953","DOIUrl":"10.1021/acs.jpcb.5c00953","url":null,"abstract":"<p><p>Passive permeation through an epithelial membrane may be enhanced by using a class of amphiphilic molecules known as permeation enhancers (PEs). PEs have been studied in clinical trials and used in coformulations with peptides and small molecule drugs, and yet, an understanding of the permeant-PE interactions leaves much to be desired. This manuscript uses all-atom molecular dynamics (MD) simulations to showcase the effects of sodium caprate (C10) and salcaprozate sodium (SNAC), two commonly applied PEs, on membrane properties and the free energy profiles of five small molecule drugs (mannitol, atenolol, ketoprofen, decanedecaol, mucic acid). Our results show that both C10 and SNAC make the lipid molecules pack more densely, but C10 increases the lipid lateral diffusivity while SNAC decreases it. The change in the lipid order parameter also shows both PEs increasing the order near the lipid heads, possibly due to the dense packing in the membrane. A decrease in the central barrier of the permeation free energy was observed by embedding PEs into a lipid bilayer and SNAC is more efficient in doing so than C10. Neither SNAC nor C10 has a large impact on the diffusion coefficient of the small molecules. The analysis of the MD simulations revealed that PEs make the membrane tail region more hydrophilic by forming hydrogen bonds with small molecule drugs, i.e., decreasing the central barrier of the permeation free energy. While this study was only limited to small molecule drugs, this lays the groundwork for future studies to which the effects of the PEs in the permeation of macromolecules and peptides may be observed.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"6188-6199"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circularly Polarized Emissive Antiferromagnetic Polymer Consisting of Ferrocene and Aniline Units.","authors":"Ryo Miyashita, Ryo Kawakami, Kanata Kimura, Aoi Tokutake, Hiromasa Goto","doi":"10.1021/acs.jpcb.5c01578","DOIUrl":"10.1021/acs.jpcb.5c01578","url":null,"abstract":"<p><p>In this study, a copolymer from 1,1'-dibromoferrocene and a chiral phenylenediamine was synthesized via Buchwald-Hartwig polycondensation. Characterization of the resulting polymer was performed by using scanning electron microscopy, optical spectroscopy, electron spin resonance, and a superconducting quantum-interference device. The polymer possesses optical activity and exhibits circularly polarized luminescence, which is attributed to the helical conjugated architecture. The polymer thus synthesized exhibits multiple spin states evaluated with electron spin resonance and antiferromagnetic behavior at low temperatures.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"6357-6362"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Dynamics of Lipid Nanoparticles Explored through Solution and Solid-State NMR Spectroscopy and MD Simulations.","authors":"Ryan Schroder, Umut Ozuguzel, Yong Du, Tyler Matthew Corts, Yong Liu, Sachin Mittal, Allen C Templeton, Bodhisattwa Chaudhuri, Marian Gindy, Angela Wagner, Yongchao Su","doi":"10.1021/acs.jpcb.5c01399","DOIUrl":"10.1021/acs.jpcb.5c01399","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) are a critical platform for nucleic acid delivery, characterized by their kinetic assemblies and structural complexity. In this study, we integrated solution and solid-state NMR with molecular dynamics (MD) simulations to probe lipid dynamics in therapeutic siRNA-encapsulated LNP formulations over a temperature range of 30 °C to -50 °C. Using ¹H-¹³C cross-polarization (CP) and insensitive nuclei enhanced by polarization transfer (INEPT) solid-state NMR experiments, we probed mobile and rigid components by analyzing ¹³C signal attenuation due to molecular motions spanning nanoseconds to seconds. Our findings demonstrate that the cationic lipid, Lipid X, exhibits significantly higher dynamics at nanosecond time scales than other lipid components, with siRNA encapsulation reducing its mobility, thereby supporting a dense core model for siRNA-loaded LNPs. In contrast, DSPC and cholesterol, which constitute the outer envelope membrane of LNP particles, exhibit slower motion compared to the cationic lipid. PEGylated lipid content strongly influences LNP membrane dynamics, displaying a broad dynamic distribution of its polyethylene glycol chains on the particle surface, as shown by relaxation-filtered Diffusion-Ordered NMR Spectroscopy (DOSY). Phase transition studies indicate that the siRNA-cationic-lipid core shifts to a slower motional state at -50 °C, evidenced by the disappearance of Lipid X ¹³C INEPT signals, whereas the DSPC/cholesterol/PEG membrane undergoes a phase change at -20 °C, marked by an increase in ¹³C CP intensity. Interestingly, the freezing of the bulk solution at -15 °C to -20 °C and the water domain within the interior core region at -35 °C to -50 °C appear to couple with the slowing of motions in the outer membrane and the siRNA-cationic-lipid complex, respectively. Complementary MD simulations provide detailed insights into lipid organization and dynamics across the examined temperature range. Collectively, these spectroscopic and computational findings deepen our molecular-level understanding of the LNP core and surface dynamics and offer valuable guidance for optimizing stable LNP formulations for therapeutic applications.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"6200-6219"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solvation Free Energies of Ion Dissociations in Dichloromethane: En Route to Accurate Computations.","authors":"Adélaïde Savoy, Eno Paenurk, Robert Pollice, Philippe H Hünenberger, Peter Chen","doi":"10.1021/acs.jpcb.5c01446","DOIUrl":"10.1021/acs.jpcb.5c01446","url":null,"abstract":"<p><p>Calculating accurate free energies for solution-phase reactions is notoriously difficult. In our previous joint experimental and computational studies, we observed a striking failure of quantum mechanical calculations with popular implicit solvent models to even qualitatively reproduce the experimental trends of dissociation free energies of numerous proton-bound pyridine dimers in organic solvents [Pollice, R. . <i>J. Am. Chem. Soc.</i> 2017, 139(37), 13126-13140]; [Pollice, R. . <i>Angew. Chem., Int. Ed.</i> 2019, 58(40), 14281-14288]. In this article, we expand the computational study of the dissociation of proton-bound pyridine dimers in the gas phase and in dichloromethane (DCM). In an effort to determine the prerequisites for reproducing the experimental trends and magnitudes of the dissociation free energies (Δ<i>G</i>_diss) in solvent, we investigated the impact of accounting for the ensemble free energy, umbrella sampling, thermodynamic integration, and explicit solvation using semiempirical quantum mechanics and molecular mechanics. We estimated the effect of conformational free energy contributions with semiempirical quantum mechanics (SE). Molecular dynamics (MD) with explicit solvation and classical molecular mechanics (MM) was used as a method to treat not only the solute but also the solvent configurational entropy. We found that explicit solvation with MM is indeed capable of reproducing Δ<i>G</i>_diss in DCM for our test system within an acceptable error margin. We analyze and discuss the results and limitations of our approach for calculating the solvation free energy.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"6276-6288"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into Formation of Bicontinuous Emulsion Gels via In Situ (Ultra-)Small Angle X-Ray Scattering.","authors":"Meyer T Alting, Dominique M E Thies-Weesie, Alexander M van Silfhout, Mariska de Ruiter, Theyencheri Narayanan, Martin F Haase, Andrei V Petukhov","doi":"10.1021/acs.jpcb.5c02375","DOIUrl":"10.1021/acs.jpcb.5c02375","url":null,"abstract":"<p><p>Nanostructured materials formed via kinetically controlled self-assembly processes gather more interest nowadays. In particular, bicontinuous emulsion gels stabilized by colloidal particles, called bijels, are attractive materials as they combine bulk properties of two immiscible liquids into an interwoven network structure. The limited understanding of the complex formation phenomena of bijels restricts the control over the synthesis, and so its applicability. In this work, in situ (ultra-) small-angle X-ray scattering is applied to gain insight into the phase separation and self-assembly kinetics of bijels formed via solvent transfer induced phase separation. An X-ray compatible microfluidic setup allows accessing the kinetics of the extrusion process with a millisecond resolution. The formation of such bijels out of a liquid precursor mixture is shown to occur via three consecutive steps. The first 7 ms of the extrusion are dominated by fluid dynamics. Then, the precursor mixture remains in an induction phase for 50 ms where nanoparticles start to self-assemble without structural development on the (sub)micron scale. From 50 ms on, an inward propagation of a liquid-liquid phase separation front occurs, besides the proceeding nanoparticle self-assembly obtaining (sub)micron-sized structures. This time-resolved monitoring technique offers valuable insights into the structural evolution of kinetically controlled materials and enhances our understanding of the formation of bicontinuous emulsion gels.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"6419-6427"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}