The Journal of Physical Chemistry B最新文献

A new library of deep eutectic solvents (DESs) was synthesized from the binary combinations of diethylammonium chloride (DEAC), choline chloride (ChCl), glycerol, malonic acid, maleic acid, urea, and niacin across diverse molar proportions by employing either of the thermal- or microwave-assisted routes. Reaction optimization demonstrated that microwave irradiation (30–40 °C, 10–20 s) yielded stable, clear liquids for most of the DEAC:glycerol systems (1:2–1:5), whereas some thermally synthesized maleic acid-urea and malonic acid-DEAC mixtures resulted in rapid postsynthesis solidification, reflecting strong composition-dependent stability constraints. FTIR characterization confirmed DES formation through marked hydrogen bonding, peak broadening, and shifts in the signal positions for more polar O–H, N–H, and C═O bonds. Moreover, a systematic pH profiling across concentration and temperature exhibited well-defined acidity trends, such as malonic-acid- and maleic-acid–based DESs, resulting in strongly acidic aqueous solutions (pH 1.3–2.2), while polyol-based DES solutions in the DEAC:glycerol series remained weakly acidic (pH 4.0–5.3), indicating distinct hydrogen-bond donor/acceptor environments and their sensitivity to aqueous media. The DESs DEAC:glycerol (1:3–1:5) and niacin:urea (1:2) were proved to be the most potent scavengers, exhibiting activity comparable to the reference standard, in antioxidant evaluation. Further, the eutectic combinations DEAC:glycerol (1:3–1:5) (80–100% inhibition at 100 mg/mL; IC₅₀ ≈ 2.0–2.5 mg/mL) demonstrated greater phytotoxicity among the screened DESs, matching the activity of benzofuran, while the DEAC:glycerol (1:2) combination was nontoxic. In antibacterial screening, the DESs DEAC:glycerol (1:3), malonic acid:DEAC (1:1), niacin:urea (1:2), and maleic acid:urea (1:1) resulted in greater activity with inhibition zones of 20–23 mm against E. coli and 20–22 mm against B. subtilis and the IC₅₀ values ranging 0.23–0.50 mg/mL which were comparable to the control, indicating strong intrinsic bioactivity arose from synergistic component interactions. Furthermore, the DFT analyses B3LYP-D3/6-31+G(d,p) corroborated experimental stability trends, thus revealing deep, cooperative hydrogen-bond networks along with low-energy gradient surfaces, which were consistent with persistent noncovalent interactions in the most stable DESs. Collectively, these outcomes establish clear structure–property–bioactivity relationships and provide mechanistic insights into how compositional tuning governs acidity, stability, and biological potency in DES systems.

Fluorescent probes are indispensable for cellular imaging and for monitoring pH-dependent biological processes. However, the majority of reported probes are effective only in near-neutral or mildly acidic ranges, with very few functioning reliably in strongly acidic environments (pH < 4). Designing water-soluble, biocompatible probes that can operate efficiently under such extreme conditions remains an important analytical challenge. To address this challenge, two pH-responsive fluorescent probes, Xpy and XpyF, based on a xanthone core, were designed and synthesized. Both probes exhibit excellent water solubility, low cytotoxicity, and strong turn-on fluorescence in acidic environments. The probes display distinct emission changes from blue at neutral to moderately acidic pH (3–7) to green at strongly acidic pH (1–2). Absolute quantum yield and TCSPC studies confirmed significant fluorescence enhancement and lifetime prolongation under acidic conditions, consistent with protonation-induced PET inhibition. Cellular imaging studies revealed efficient internalization and strong nuclear localization with high Pearson’s correlation coefficients. Importantly, while Xpy showed consistent nuclear staining across pH values, XpyF demonstrated a unique pH-dependent switch from cytoplasmic localization at pH 7.4 to nuclear accumulation at pH 4.3. Overall, Xpy and XpyF represent reliable nuclear-targeting sensors for strongly acidic media, illustrating how subtle structural modifications can yield distinct functional outcomes in bioimaging.

Dynamic surface tension γ(t) is widely measured but often interpreted with system-specific models that obscure general design rules. We develop a minimal kinetic–thermodynamic framework that couples two-rate adsorption–desorption with the Gibbs adsorption relation and Arrhenius temperature dependence, and validate it on ionic (SDS, CTAB) and nonionic (Tween 80) surfactants by force tensiometry from 10–80 °C (10, 20, 30, 40, 60, and 80 °C) across sub- to supra-CMC concentrations, with full uncertainty propagation. A single closed-form expression reproduces γ(t, T, C_b) with R² ≥ 0.99. A Damköhler group, Da_γ = k_a C_b/k_d, partitions regimes (desorption-limited <1; balanced ≈ 1; adsorption-dominated >10). Extracted trends show k_a increases approximately linearly with C_b up to the CMC, while k_d ≈ 10^–2–10^–3 s^–1 remains nearly constant; Arrhenius fits yield consistent activation energies, and the entropy-generation rate Ṡ_gen = −T^–1dγ/dt peaks early then relaxes toward zero, confirming thermodynamic consistency. The framework maps raw γ(t) to rate constants, energy barriers, and regime labels, enabling rational selection of surfactant chemistry, concentration, and temperature to achieve rapid interfacial equilibration in sprays, coatings, emulsification, and related processes.

We employ isoconversional analysis to gain insights on aging time-dependent thermal barriers in glasses evolving toward equilibrium. This is applied to glasses of different natures, including small molecules and polymers. Our analysis indicates that as relaxation proceeds, equilibration kinetics involves increasingly larger activation barriers. The latter equals that of the α-relaxation at the final stage of aging. In contrast, the relatively low thermal barriers at the initial and intermediate stages of aging indicate that mechanisms different from the α-relaxation mediate aging in these conditions. We discuss the nature of these mechanisms in the light of the complexity of glass aging.

Abnormal aggregation of microtubule-associated protein tau into β-sheet-rich fibrils is a hallmark feature of Alzheimer’s disease and other tauopathies. The pathogenic P301L mutation within the microtubule-binding domain of tau promotes tau filament formation; however, the molecular mechanisms by which intracellular RNAs regulate this aggregation process remain not fully understood. Here, we investigated the mechanistic effects of RNA homopolymers on the aggregation of a tau fragment peptide (residues 298–317) derived from the microtubule-binding region and its P301L mutant. The results showed that while the wild-type peptide remained resistant to aggregation in the presence of RNA, pyrimidine-rich RNAs (poly(C) and poly(U)) significantly accelerated fibrillation of the P301L mutant. The mutation likely disrupts the local conformational constraints, leading to a more flexible conformation and exposure of hydrophobic residues. This facilitates intermolecular interactions to form β–sheet–rich aggregates after RNA-induced local condensation and alignment of the peptide as a nucleation scaffold for aggregation. In contrast, purine-rich RNAs (poly(A) and poly(G)) had negligible effects on P301L mutant aggregation, suggesting that the specific chemical and conformational properties of RNA, such as base structures, geometrical arrangement, and base stacking, in addition to its polyanionic nature, are critical determinants of its ability to modulate tau peptide amyloid formation. Furthermore, the polycationic molecules spermine and polyarginine effectively delayed or inhibited RNA-induced aggregation, indicating that rationally designed polycations could serve as valuable modulators of RNA-mediated fibrillation within the crucial tau aggregation-prone region.

Targeted protein degradation via PROTACs (PROteolysis TArgeting Chimaeras) has transformed drug discovery by enabling the elimination of disease-driving proteins, including those previously considered undruggable. However, rational PROTAC design remains hindered by the lack of systematic approaches to evaluate the geometry of ternary complexes, ubiquitination feasibility, and the influence of linker architecture on degradation potential. Here, we present an integrative computational framework that addresses these challenges by combining ternary complex generation, pairwise RMSD-based clustering, full CRL2^VHL RING-like complex modeling, lysine proximity analysis, and structure-guided dynamics. As a representative system, we applied this workflow to PTP1B, a phosphatase implicated in oncogenic signaling yet long considered therapeutically challenging. Over 6900 ternary complex poses were generated across diverse linker designs and systematically filtered using custom Python scripts that automate pose clustering and lysine-to-E2 distance evaluation. Critical ternary complexes were subjected to molecular dynamics simulations, PCA, TICA, and Markov state modeling to reveal degradation-competent conformations and dynamic transitions. We additionally assessed AlphaFold-Multimer and Arg69-guided docking approaches. AlphaFold-Multimer produced few lysine-accessible poses, whereas Arg69-guided docking enriched degradation-competent geometries via biologically relevant interactions. This framework offers a mechanistically grounded and generalizable strategy for rational PROTAC development across protein targets.

Directed motion of particles is typically explained by phoretic mechanisms arising under externally imposed chemical, electric, or thermal gradients. In contrast, chemical reactions can enhance particle diffusion even in the absence of such external gradients. We refer to this increase as active diffusivity, often attributed to self-diffusiophoresis or self-electrophoresis, although these mechanisms alone do not fully account for experimental observations. Here, we investigate active diffusivity in catalytic Janus particles immersed in reactive media without imposed gradients. We show that interfacial reactions generate excess surface energy and sustained interfacial stresses that supplement thermal energy, enabling diffusion beyond the classical thermal limit. We consistently quantify this contribution using both dissipative and nondissipative approaches, assuming that the aqueous bath remains near equilibrium. Our framework reproduces experimentally observed trends in diffusivity versus activity, including the nonmonotonic behaviors reported in some systems, and agrees with data for nanometric Janus particles catalyzing charged substrates as well as vesicles with membrane-embedded enzymes driven by ATP hydrolysis. These results demonstrate that chemical reactions can induce and sustain surface-tension gradients and surface excess energy, providing design principles for tuning mobility in synthetic active matter.

Chemical inhibitors bind to enzymes, thereby inhibiting their catalytic activity. While many enzymes catalyze reactions with a single substrate, others, like DNA polymerase, can act on multiple related substrates. Substrate-selective inhibitors (SSIs) target these multisubstrate enzymes to modulate their specificity. Although SSIs hold promise as therapeutics, our theoretical understanding of how different inhibitors influence enzyme specificity remains limited. In this study, we examine enzyme selectivity within kinetic networks corresponding to known inhibition mechanisms. We demonstrate that competitive and uncompetitive inhibitors do not affect substrate specificity, regardless of rate constants. In contrast, noncompetitive and mixed inhibition can alter specificity and can lead to nonmonotonic responses to the inhibitor. We show that mixed and noncompetitive inhibitors achieve substrate-selective inhibition by altering the effective free-energy barriers of product formation pathways that are enabled by the inhibitor’s presence. We then apply this framework to the Sirtuin-family deacylase SIRT2, showing that the suicide inhibitor thiomyristoyl lysine (TM) cannot influence substrate specificity unless there is a direct substrate exchange reaction or biochemical constraints are relaxed. These findings provide insights into engineering systems where cofactor binding modulates metabolic flux ratios.

Cold crystallization, an exothermic phase transition upon heating of a glassy state, is of interest in heat storage materials. While such behavior is common in polymers, small-molecule systems have also been investigated. Herein, we report a semiflexible macrocyclic compound composed of four silyl ether units and aromatic linkers that exhibits distinct cold crystallization. A key for the molecular design is semiflexible silyl ether units significantly affecting the macrocyclic shape. Differential scanning calorimetry revealed the formation of a glassy state by melt quenching, followed by exothermic crystallization. Powder X-ray diffraction indicated that the molecular conformation and packing in the crystals after cold crystallization are similar to those of solution-grown crystals. In contrast, a biphenylene-bridged macrocycle and a reference compound with a nonmacrocyclic structure did not show this behavior. These results suggest that a macrocyclic structure with suitable conformational mobility may help in the design of small molecular systems showing cold crystallization as heat storage materials.

The ability of alcohols to perturb the structure and function of membrane bilayers and membrane proteins has made them indispensable in the pharmaceutical and biochemical industry. In the present study, we delineate the bilayer-modifying potency of trifluoroethanol (TFE), a fluorinated analogue of widely used ethanol (EtOH), toward biomimetic lipid membranes composed of pure 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and POPC/cholesterol (POPC/CHOL) lipids using experimental techniques and atomistic molecular dynamics simulations. Our field emission scanning electron microscopy results show the appearance of small particles on the surface of POPC liposome in the presence of 60 v/v% EtOH or TFE, which is otherwise smooth, indicating alcohol-mediated structural modification in the liposome. Dynamic light scattering measurements reveal liposome enlargement at the lower alcohol concentrations and the presence of smaller globules at high concentrations of TFE. The simulation results reveal that the POPC bilayer with TFE suffers the highest degree of perturbation (complete rupture) beyond 50 v/v% concentration, followed by POPC/CHOL-TFE, POPC-EtOH systems, and binary POPC/CHOL bilayer with ethanol partially retaining its bilayer structure at a given concentration. Lipid tail order parameters reveal that TFE induces more disorder in lipids than EtOH for both the POPC and POPC/CHOL systems. Density profiles along the bilayer normal show the loss of bilayer structure with increasing alcohol concentration, with TFE mediating a higher degree of structural disruption at the same concentrations. The higher detrimental impact of TFE on lipid bilayers is attributed to extensive H-bonding and stronger attractive nonpolar interaction between lipid and TFE molecules, leading to weaker lipid–lipid interaction in the presence of TFE and exceptionally high TFE–TFE electrostatic repulsion when compared to its nonfluorinated counterpart.