The Journal of Physical Chemistry B最新文献

The photophysics of carotenoids has long been obscured by the elusive assignment of their low-lying excited states, particularly the origin of the so-called S* feature. Using mixed-reference spin-flip time-dependent density functional theory (MRSF-TDDFT) combined with nonadiabatic molecular dynamics (NAMD), we uncover geometry-dependent reordering of the bright 1¹B_u⁺ and dark 2¹A_g^- states in both polyenes and lutein. Upon slight excited-state geometric relaxation, the 1¹B_u⁺ state initially lies below the 2¹A_g^- state. Subsequent BLA-driven internal conversion then drives the system toward the 2¹A_g^- minimum region, where the energetic ordering is reversed and the 2¹A_g^- state becomes lower than the 1¹B_u⁺ state. NAMD trajectories of lutein further capture the ultrafast dynamic interconversion equilibrium between 1¹B_u⁺ and 2¹A_g^-, indicating their coexistence during the early stages of photoexcitation. Within this framework, excited-state absorption (ESA) simulations of lutein indicate that the intense low-energy transient band, traditionally assigned to S₁ with the 2¹A_g^- character, instead arises from a minor residual population with the 1¹B_u⁺ character, whereas the weaker, higher energy band previously assigned to S* originates from the global-minimum 2¹A_g,min^- structure and is dominated by the 2¹A_g^- character. This reinterpretation naturally resolves several puzzling experimental observations. Thus, the geometry-sensitive state ordering and the coexistence model established through internal conversion equilibrium open a new avenue for understanding the fundamental features of these systems and provide a fresh framework for interpreting experimental observations.

A quantitative approach is developed to the study of the spatial distribution of amino acid mobility in protein structures. This method, which is based on bioinformatic and signal processing tools, makes it possible to study very large databases of structures simultaneously, and to search for the existence of domains within proteins which are defined by mobility effects, rather than by static structural considerations. It is shown that mobility is distributed nonuniformly in a substantial subset of structures in a large database; that nonuniform mobility distribution does not select for fold class; and that differences in local mobility distribution are correlated with differences in total mobility. Analyzed in light of previous results, these findings suggest that the dynamics of proteins with nonuniform distributions of mobility may exhibit dynamics dominated by local modes, rather than large-scale motions. We suggest that spatial mobility distribution may be a significant driver of protein evolution. It is also speculated that mobility distribution may act as a control on the hydrodynamic environment of proteins in solution.

The global transition to hydrogen-based energy infrastructures faces significant hurdles. Chief among these are the high costs and sustainability issues associated with acid–based proton exchange membrane fuel cells. Anion exchange membrane (AEM) fuel cells offer promising cost-effective alternatives, yet their widespread adoption is limited by rapid degradation in alkaline environments. Here, we develop a framework that integrates mechanistic insights with machine learning, enabling the identification of generalized degradation behavior across diverse polymeric AEM chemistries and operating conditions. Our model successfully predicts long-term hydroxide conductivity degradation (up to 10,000 h) from minimal early time experimental data. This capability significantly reduces experimental burdens and may expedite the design of high-performance, durable AEM materials.

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.