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The size distribution and morphology evolution of the initial agglomerates on the burning surface of aluminized composite propellants have a strong influence on the agglomeration mechanism and size of condensed products. However, most previous research has focused on the establishment of size prediction models, and research on other characteristics of initial agglomerates is still lacking. The characteristics of the size distribution and evolution of the morphology of the initial agglomerates are investigated in this study. Analysis of the size distribution of the initial agglomerates shows that the distribution is regular in the stable combustion stage, and the agglomerates in this stage show weak agglomeration. The morphologies of the initial agglomerates are found to comprise coral-like structures composed of small alumina particles with strong fluidity in Stage (a), in which the effect of accumulation is dominant. In Stage (b), the initial agglomerates exhibit a relatively stable form of a ‘spherical structure + coral-like bond’, and the effects of accumulation and combustion are in dynamic equilibrium. In Stage (c), the initial agglomerates are spherical with an oxidation cap, and this stage is dominated by combustion. Through analysis of the characteristics of the size distribution and morphology evolution of the initial agglomerates, the agglomeration mechanism of aluminum particles on the burning surface is further clarified, which provides the foundation for further research.

G-quadruplexes have become attractive drug targets in cancer therapy. However, due to the polymorphism of G-quadruplex structures, it is difficult to experimentally verify the relevant structures of multiple intermediates and transition states in dynamic equilibrium. Hence, understanding the mechanism by which structural conversions of G-quadruplexes occur is still challenging. We conducted targeted molecular dynamics simulation with umbrella sampling to investigate how salt affects the conformational conversion of human telomeric G-quadruplex. Our results explore a unique view into the structures and energy barrier of the intermediates and transition states in the interconversion process. The pathway of G-quadruplex conformational interconversion was mapped out by a free energy landscape, consisting of branched parallel pathways with multiple energy basins. We propose a salt-controlled mechanism that as the salt concentration increases, the conformational conversion mechanism switches from multi-pathway folding to sequential folding pathways. The hybrid-I and hybrid-II structures are intermediates in the basket-propeller transformation. In high-salt solutions, the conformational conversion upon K+ binding is more feasible than upon Na+ binding. The free energy barrier for conformational conversions ranges from 1.6 to 4.6 kcal/mol. Our work will be beneficial in developing anticancer agents.

Fatty acid binding proteins (FABPs) can facilitate the transfer of long-chain fatty acids between intracellular membranes across considerable distances. The transfer process involves fatty acids, their donor membrane and acceptor membrane, and FABPs, implying that potential protein-membrane interactions exist. Despite intensive studies on FABP-membrane interactions, the interaction mode remains elusive, and the protein-membrane association and dissociation rates are inconsistent. In this study, we used nanodiscs (NDs) as mimetic membranes to investigate FABP-membrane interactions. Our NMR experiments showed that human intestinal FABP interacts weakly with both negatively charged and neutral membranes, but it prefers the negatively charged one. Through simultaneous analysis of NMR relaxation in the rotating-frame (R(1ρ)), relaxation dispersion, chemical exchange saturation transfer, and dark-state exchange saturation transfer data, we estimated the affinity of the protein to negatively charged NDs, the dissociation rate, and apparent association rate. We further showed that the protein in the ND-bound state adopts a conformation different from the native structure and the second helix is very likely involved in interactions with NDs. We also found a membrane-induced FABP conformational state that exists only in the presence of NDs. This state is native-like, different from other conformational states in structure, unbound to NDs, and in dynamic equilibrium with the ND-bound state.

In duplex DNA, Watson–Crick A–T and G–C base pairs (bp's) exist in dynamic equilibrium with an alternative Hoogsteen conformation, which is low in abundance and short-lived. Measuring how the Hoogsteen dynamics varies across different DNA sequences, structural contexts and physiological conditions is key for identifying potential Hoogsteen hot spots and for understanding the potential roles of Hoogsteen base pairs in DNA recognition and repair. However, such studies are hampered by the need to prepare 13 C or 15 N isotopically enriched DNA samples for NMR relaxation dispersion (RD) experiments. Here, using SELective Optimized Proton Experiments (SELOPE) 1 H CEST experiments employing high-power radiofrequency fields ( B1 > 250 Hz) targeting imino protons, we demonstrate accurate and robust characterization of Watson–Crick to Hoogsteen exchange, without the need for isotopic enrichment of the DNA. For 13 residues in three DNA duplexes under different temperature and pH conditions, the exchange parameters deduced from high-power imino 1 H CEST were in very good agreement with counterparts measured using off-resonance 13 C / 15 N spin relaxation in the rotating frame ( R1ρ ). It is shown that 1 H– 1 H NOE effects which typically introduce artifacts in 1 H-based measurements of chemical exchange can be effectively suppressed by selective excitation, provided that the relaxation delay is short ( ≤ 100 ms). The 1 H CEST experiment can be performed with ∼ 10 × higher throughput and ∼ 100 × lower cost relative to 13 C / 15 N R1ρ and enabled Hoogsteen chemical exchange measurements undetectable by R1ρ . The results reveal an increased propensity to form Hoogsteen bp's near terminal ends and a diminished propensity within A-tract motifs. The 1 H CEST experiment provides a basis for rapidly screening Hoogsteen breathing in duplex DNA, enabling identification of unusual motifs for more in-depth characterization.

Today, there is a greater appreciation for the importance of the physical protection of carbon (C) through interactions with mineral surfaces, isolation from microbes, and the important role of transport in shaping soil properties and controlling moisture limitations on decomposition. As our paradigm for soil organic carbon (SOC) preservation changes, so too should our representation of the underlying processes in soil models. Reactive transport models (RTMs) provide a framework capable of assessing the interactive influence of soil chemistry and transport processes on the accumulation and turnover of SOC. In this study, we present new developments in the isotopically enabled RTM “CrunchTope,” which is capable of explicitly tracking the three isotopes of carbon (12C, 13C, and 14C) and their fractionation between multiple coexisting and interacting solid, liquid and gas phases. This modeling framework opens the door to new applications of depth-resolved RTM models in application to SOC and deeper subsurface carbon reservoirs. Here, we demonstrate SOC accumulation and radiocarbon aging for long-timescale models of soil development in CrunchTope. Our goal is to assess advantages and limitations of such an approach and to identify the type and complexity of reaction networks that are required to adequately apply this model to SOC dynamics. We assess the behavior of this model relative to a high-resolution dataset of SOC content, stable isotope composition, and radiocarbon ages as well as physical and hydrologic data measured from a chronosequence of soils located near Santa Cruz, California. Starting from a previously published model using a simplified reaction network with a single class of carbon, we sequentially incorporate multiple carbon reservoirs subject to both reactivity and transport pathways. Our results indicate that multiple SOC pools with different mean ages of C do not inherently emerge as a result of including reactions which are conventionally expected to provide a diversity of transit times, i.e., sorption and complexation of SOC on mineral surfaces. Instead, transit times emerge as a result of the timescales of the reactions represented in the reaction network. For mineral associated C, the RTM framework imposes dynamic equilibrium with the fluid phase dissolved organic carbon, such that no distinction in radiocarbon ages is achieved between these pools. Aged C can be produced by including a solid-phase carbon reservoir, with a rate-limited solubilization coefficient. Aging of SOC in this way is more akin to selective preservation than to mineral protection and, while such a mechanism may be at play in many soils, mineral protection is thought to be at least as important. As such, our results indicate that additional parameterization is required to reproduce the heterogeneity of carbon transit times that result from organo-mineral interactions. These efforts show the promise of a modeling approach where the varied transit time of soil C emerges from the dynamic physical and hydrologic properties of the model rather than from the a priori assignment of operationally defined pools.

The MARTINI model is a widely used coarse-grained force field popular for its capacity to represent a diverse array of complex biomolecules. However, efforts to simulate increasingly realistic models of membranes, involving complex lipid mixtures and multiple proteins, suggest that membrane protein aggregates are overstabilized by the MARTINI v2.2 force field. In this study, we address this shortcoming of the MARTINI model. We determined the free energy of dimerization of four transmembrane protein systems using the nonpolarizable MARTINI model. Comparison with experimental FRET-based estimates of the dimerization free energy was used to quantify the significant overstabilization of each protein homodimer studied. To improve the agreement between simulation and experiment, a single uniform scaling factor, α, was used to enhance the protein–lipid Lennard–Jones interaction. A value of α = 1.04–1.045 was found to provide the best fit to the dimerization free energies for the proteins studied while maintaining the specificity of contacts at the dimer interface. To further validate the modified force field, we performed a multiprotein simulation using both MARTINI v2.2 and the reparameterized MARTINI model. While the original MARTINI model predicts oligomerization of protein into a single aggregate, the reparameterized MARTINI model maintains a dynamic equilibrium between monomers and dimers as predicted by experimental studies. The proposed reparameterization is an alternative to the standard MARTINI model for use in simulations of realistic models of a biological membrane containing diverse lipids and proteins.

Electron transfer is the rate-limiting step in photocatalytic water splitting. Viologen and its derivatives are able to act as electron-transfer mediators (ETMs) to facilitate the rapid electron transfer from photosensitizers to active sites. Nevertheless, the electron-transfer ability often suffers from the formation of a stable dipole structure through the coupling between cationic-radical-containing viologen-derived ETMs, by which the electron-transfer process becomes restricted. Herein, cyclic diquats, a kind of viologen-derived ETM, are integrated into a 2,2'-bipyridine-based covalent organic framework (COF) through a post-quaternization reaction. The content and distribution of embedded diquat-ETMs are elaborately controlled, leading to the favorable site-isolated arrangement. The resulting materials integrate the photosensitizing units and ETMs into one system, exhibiting the enhanced hydrogen evolution rate (34600 μmol h-1 g-1 ) and sustained performances when compared to a single-module COF and a COF/ETM mixture. The integration strategy applied in a 2D COF platform promotes the consecutive electron transfer in photochemical processes through the multi-component cooperation.

Vast G-quadruplexes (GQs) are primarily folded by one, two, or four G-rich oligomers, rarely with an exception. Here, we present the first NMR solution structure of a trimolecular GQ (tri-GQ) that is solely assembled by the self-trimerization of d(GTTAGG), preferentially in Na+ solution tolerant to an equal amount of K+ cation. Eight guanines from three asymmetrically folded strands of d(GTTAGG) are organized into a two-tetrad core, which features a broken G-column and two width-irregular grooves. Fast strand exchanges on a timescale of second at 17°C spontaneously occur between folded tri-GQ and unfolded single-strand of d(GTTAGG) that both species coexist in dynamic equilibrium. Thus, this tri-GQ is not just simply a static assembly but rather a dynamic assembly. Moreover, another minor tetra-GQ that has putatively tetrameric (2+2) antiparallel topology becomes noticeable only at an extremely high strand concentration above 18 mM. The major tri-GQ and minor tetra-GQ are considered to be mutually related, and their reversible interconversion pathways are proposed accordingly. The sequence d(GTTAGG) could be regarded as either a reading frame shifted single repeat of human telomeric DNA or a 1.5 repeat of Bombyx mori telomeric DNA. Overall, our findings provide new insight into GQs and expect more functional applications.

У статті проведено дослідження щодо впливу електрично активних дефектів на термостимульовані струми в кристалах дифосфіду цинку. Відомо, що зростання електропровідності у напівпровідникових матеріалах відбувається двома шляхами: за рахунок підвищення їх температури, а також через зріст кількісті домішок та дефектів у кристалах цих матеріалів. З цієї точки зору до перспективних напівпровідникових матеріалів можна віднести кристали дифосфіду цинку та кадмію. У нашому випадку у якості об’єкту дослідження були обрані кристали α - ZnP2. У тетрагональних кристалах дифосфіду цинку, які були вирощені методом сублімації у двох температурній печі, виявлені електрично активні дефекти, що обумовлюють появу релаксаційних струмів короткого замикання у процесі нагріву. Спонтанна поляризація, що генерує термостимульовані струми короткого замикання, викликана порушеннями динамічної рівноваги в електронній та гратковій підсистемах кристалу α - ZnP2. Наведено, що динамічна рівновага між електронною та гратковою пілсистемами визначає характер змін властивостей напівпровідникових кристалів. У свою чергу, зміна ж швидкості у процесах нагрівання безсумнівно приводитимо до порушення динамічної рівноваги між цими підсистемами та, отже, і до появи термостимульованих струмів. У ході дослідження виявлена здатність цих кристалів утворювати спонтанну поляризацію, яка приводить до появи термостимульованих струмів короткого замикання у напрямку (001). Це явище обумовлено не фазовими температурними переходами, як уявлялося раніше, а, найімовірніше, у результаті домішкових викривлень кристалічної гратки при її нагріві, які призводять до порушення динамічної рівноваги у електронній та гратковій підсистемах кристалу за рахунок появи електрично активних дефектів. Ключові слова: пониженні симетричні кристали, електрично активні дефекти, термостимульовані струми.

Glycolaldehyde (HOCH2CHO, GA), the simplest molecule containing both hydroxyl and aldehyde groups, is structurally the most elementary member of monosaccharide sugars, which may provide new clues for probing the origin of life on planets like the Earth. Uncovering the existing state of GA in solution systems is an important scientific issue. Generally, methanol is used as the main mobile phase in the liquid chromatography analysis of GA, but the state of GA existing in methanol solution remains unknown, thus making it difficult to analyse GA accurately. Herein, the state and dynamic equilibrium of GA in methanol solution were systematically studied by UV-visible spectroscopy, nuclear magnetic resonance (1H-NMR) spectroscopy, liquid chromatography mass spectrometry (LC–MS) and density functional theory (DFT) calculations. The results demonstrated that the equilibrium component of GA in methanol solution is different from that in aqueous solution and that glycolaldehyde hemiacetal (GAHA) is a dominant component (>90%). Laying the foundation for experimental analysis, the transformation of different components at equilibrium was studied using DFT. The results confirm that hydrogen bonding-induced proton transfer occurs between the components at equilibrium. This work provides an important reference for the analysis of sugars and related compounds in various biochemical reactions.

The ability to prepare block, multiblock and segmented polymers is an essential and established tool in polymer chemistry to tailor the properties of materials and steer the formation of complex nanostructures. The preparation of segmented or block copolymers with pre-defined block lengths is, however, inherently difficult for polyimides, one of the most important and versatile high-performance polymers. The most accessible route to polyimides, a step-growth polyamic acid formation between diamines and dianhydrides, is in dynamic equilibrium, which leads to chain scrambling of attempted block copolymers. We provide herein a solution to this by utilizing a Diels–Alder reaction on phenylethynyl end-functionalized oligomers containing pre-formed, ring-closed imides. The reaction of the alkynes with a bistetraphenylcyclopentadienone chain extender undergoes a chelotropic evolution of CO gas at high temperatures forming phenylene segments and polymerizing the chains in the process. Furthermore, we could use this reaction for the chain extension of different phenylethynyl functionalized telechelic oligoimides and thus produce random multiblock copolymers. Importantly the reaction is also demonstrated to enable chain extension reactions with insoluble oligoimides, considerably expanding the scope of potential as many important polyimides are either insoluble, or poorly soluble, in common organic solvents. This Diels–Alder polymerization is thus demonstrated to be a highly versatile route to prepare novel polyimides with wide-ranging possibilities and considerable potential to prepare advanced materials ranging from electronic applications to high-performance materials.

The re-release process and the release rate of heavy metals, cadmium and plumbum, which are rich in sediments of a certain water area, were investigated using a combined experimental and numerical method. Results show that the release law of Cd and Pb in sediments is divided into two stages: rapid release and dynamic equilibrium, which is in great agreement with the pseudo second-order kinetic equation with a correlation coefficient R2 above 0.99. As the flow velocity accelerates, the release rate of heavy metals increases. The analysis results indicate that the water quality in the area can exceed the surface water Class V standard less than 3 h, and all but one of the relative deviations between the simulation value and the field survey result are within ±10%.

Mechanically induced migration of grain boundaries and triple junctions not only determines the size and shape of nanostructures created by severe plastic deformation, it substantially affects their mechanical properties as well. Grain growth during deformation of nanostructures has been widely observed. As the nanostructures processed by severe plastic deformation are a consequence of a dynamic equilibrium between refinement and local mechanically induced coarsening, it is widely accepted that such nanostructures would remain stable upon further loading. However, pronounced grain coarsening can be observed when pure UFG copper prepared by high pressure torsion (HPT) is additionally cold rolled. The coarsening continues up to rolling strains, e = 1, i.e. until favourable grain orientations for rolling are developed. For larger strains subsequent refinement to minimum boundary spacing identical to the HPT microstructure is observed. Interestingly, less grain growth is observed for two other sample orientations of the HPT microstructure which are rolled along different directions with respect to the sample coordinate frame. Crystallographic texture of these samples were favourable with respect to the new strain path, highlighting its role for mechanically induced growth and suggesting a distinct influence of grain orientation on the mechanically induced coarsening process.

NMR off-resonance R1ρ relaxation dispersion measurements on base carbon and nitrogen nuclei have revealed that wobble G·T/U mismatches in DNA and RNA duplexes exist in dynamic equilibrium with short-lived, low-abundance, and mutagenic Watson–Crick-like conformations. As Watson–Crick-like G·T mismatches have base pairing geometries similar to Watson–Crick base pairs, we hypothesized that they would mimic Watson–Crick base pairs with respect to the sugar-backbone conformation as well. Using off-resonance R1ρ measurements targeting the sugar C3′ and C4′ nuclei, a structure survey, and molecular dynamics simulations, we show that wobble G·T mismatches adopt sugar-backbone conformations that deviate from the canonical Watson–Crick conformation and that transitions toward tautomeric and anionic Watson–Crick-like G·T mismatches restore the canonical Watson–Crick sugar-backbone. These measurements also reveal kinetic isotope effects for tautomerization in D2O versus H2O, which provide experimental evidence in support of a transition state involving proton transfer. The results provide additional evidence in support of mutagenic Watson–Crick-like G·T mismatches, help rule out alternative inverted wobble conformations in the case of anionic G·T−, and also establish sugar carbons as new non-exchangeable probes of this exchange process.

Plutonium (Pu) exhibits a complex redox behavior in aqueous solutions. This is due to the ability of the element to adapt a wide range of oxidation states typically from +3 to +6 and the tendency for dynamic interconversion between the oxidation states that primarily depend upon acid concentration and presence of coordinating ligands. This work interrogates the Pu redox behavior in aqueous nitric acid via a combination of voltammetry and in situ vis-NIR spectroelectrochemistry under controlled potentials to map the interconversion between the various Pu oxidation states. The NIR-spectroelectrochemistry studies used to complement the visible spectroscopy bring a new and more complete perspective into the plutonium redox transformations. This allows elucidation of the mechanisms of the involved redox reactions facilitating an in-depth understanding of the relative stability of the Pu oxidation states as a function of redox potentials and nitric acid concentrations. It is observed that oxidation of Pu(III) results in generation of Pu(IV) and Pu(VI) (the latter as PuO22+), bypassing the Pu(V) oxidation state. Further, with increasing acid concentrations, the formation of the Pu(VI) species progressively decreases so that the dynamic equilibrium between the Pu(III) and Pu(IV) oxidation states dominates. These findings have significant implications for developing separation processes for used nuclear fuel reprocessing and treatment.

The ability of cucurbit[6]uril (CB6) and cucurbit[7]uril (CB7) to catalyze the thermally activated 1,2-methyl shift isomerization pathway of m-xylene in vacuum is investigated using infrequent metadynamics. CB6 is predicted to effectively and selectively catalyze the meta-to-para isomerization through stabilization of the transition state (TS) by van der Waals push (packing coefficient ≈74%), while inhibiting the meta-to-ortho pathway by molding effects of the cavity. Interestingly, despite the snug binding, a very low rate of host–guest vibrational energy transfer is revealed using a novel approach of host–guest partition of the mode-specific anharmonic relaxation rates and ab initio molecular dynamics. The weak vibrational coupling suggests that CB can act as a thermal buffer, possibly shielding encapsulated guests from outside vibrational perturbations such as solvent effects. This dynamic effect could provide an additional boost to the reaction rate by blocking the occurrence of reaction barrier recrossing caused by the friction with surrounding molecules. Finally, mean residence times of xylene into the hosts’ cavity were estimated for a range of host–guest complexes, revealing a highly dynamic equilibrium allowing very high guest turnover rates that could minimize catalyst inhibition effects commonly suffered by other supramolecular catalysts.

Intrinsically disordered proteins (IDPs) carry out many biological functions. They lack a stable three-dimensional structure, but rather adopt many different conformations in dynamic equilibrium. The interplay between local dynamics and global rearrangements is key for their function. In IDPs, proline residues are significantly enriched. Given their unique physicochemical and structural properties, a more detailed understanding of their potential role in stabilizing partially folded states in IDPs is highly desirable. Nuclear magnetic resonance (NMR) spectroscopy, and in particular 13C-detected NMR, is especially suitable to address these questions. We applied a 13C-detected strategy to study Osteopontin, a largely disordered IDP with a central compact region. By using the exquisite sensitivity and spectral resolution of these novel techniques, we gained unprecedented insight into cis-Pro populations, their local structural dynamics, and their role in mediating long-range contacts. Our findings clearly call for a reassessment of the structural and functional role of proline residues in IDPs. The emerging picture shows that proline residues have ambivalent structural roles. They are not simply disorder promoters but rather can, depending on the primary sequence context, act as nucleation sites for structural compaction in IDPs. These unexpected features provide a versatile mechanistic toolbox to enrich the conformational ensembles of IDPs with specific features for adapting to changing molecular and cellular environments.

This study presents a method that establishes the existence of competitive adsorption between polycarboxylate ether (PCE) molecules with different molecular architecture. By combining well-established total organic carbon measurements with UV–Visible absorption, competition between PCEs of different structures could be quantified. Results are interpreted by deriving a fundamental thermodynamic model describing the PCE competition as a dynamic equilibrium between adsorbed and dissolved PCE molecules with different architectures. The model rationalizes the effect of dispersity in charge and backbone length on the adsorption behavior of PCEs and contributes to a fundamental understanding of the PCE working mechanism on the molecular level., Cement and Concrete Research, 151, ISSN:0008-8846

During high-pressure torsion (HPT) the dynamic equilibrium establishes with a certain steady-state composition of the solid solution along with the grain refinement by a factor of more than thousand. The formation of such HPT steady-state in copper alloys with Co, Ag and In has been studied. If precipitates of a second phase were present in the sample before HPT, their dissolution led to the enrichment in the (Cu) matrix solid solution. If precipitates of a second phase were absent, the HPT led to the depletion in the (Cu) matrix due to the segregation in newly formed defects like grain boundaries.

The mechanism of separation methods, for example, liquid chromatography, is realized through rapid multiple adsorption-desorption steps leading to the dynamic equilibrium state in a mixture of molecules with different partition coefficients. Sorting of colloidal particles, including protein complexes, cells, and viruses, is limited due to a high energy barrier, up to millions kT, required to detach particles from the interface, which is in dramatic contrast to a few kT for small molecules. Such a strong interaction renders particle adsorption quasi-irreversible. The dynamic adsorption-desorption equilibrium is approached very slowly, if ever attainable. This limitation is alleviated with a local oscillating repulsive mechanical force generated at the microstructured stimuli-responsive polymer interface to switch between adsorption and mechanical-force-facilitated desorption of the particles. Such a dynamic regime enables the separation of colloidal mixtures based on the particle-polymer interface affinity, and it could find use in research, diagnostics, and industrial-scale label-free sorting of highly asymmetric mixtures of colloids and cells.

The CorA family of proteins regulates the homeostasis of divalent metal ions in many bacteria, archaea, and eukaryotic mitochondria, making it an important target in the investigation of the mechanisms of transport and its functional regulation. Although numerous structures of open and closed channels are now available for the CorA family, the mechanism of the transport regulation remains elusive. Here, we investigated the conformational distribution and associated dynamic behaviour of the pentameric Mg2+ channel CorA at room temperature using small-angle neutron scattering (SANS) in combination with molecular dynamics (MD) simulations and solid-state nuclear magnetic resonance spectroscopy (NMR). We find that neither the Mg2+-bound closed structure nor the Mg2+-free open forms are sufficient to explain the average conformation of CorA. Our data support the presence of conformational equilibria between multiple states, and we further find a variation in the behaviour of the backbone dynamics with and without Mg2+. We propose that CorA must be in a dynamic equilibrium between different non-conducting states, both symmetric and asymmetric, regardless of bound Mg2+ but that conducting states become more populated in Mg2+-free conditions. These properties are regulated by backbone dynamics and are key to understanding the functional regulation of CorA.

The biophysical mechanism of the magnetic compass sensor in migratory songbirds is thought to involve photo-induced radical pairs formed in cryptochrome (Cry) flavoproteins located in photoreceptor cells in the eyes. In Cry4a – the most likely of the six known avian cryptochromes to have a magnetic sensing function – four radical pair states are formed sequentially by the stepwise transfer of an electron along a chain of four tryptophan residues to the photo-excited flavin. In purified Cry4a from the migratory European robin, the third of these flavin-tryptophan radical pairs is more magnetically sensitive than the fourth, consistent with the smaller separation of the radicals in the former. Here, we explore the idea that these two radical pair states of Cry4a could exist in rapid dynamic equilibrium such that the key magnetic and kinetic properties are weighted averages. Spin dynamics simulations suggest that the third radical pair is largely responsible for magnetic sensing while the fourth may be better placed to initiate magnetic signalling particularly if the terminal tryptophan radical can be reduced by a nearby tyrosine. Such an arrangement could have allowed independent optimisation of the essential sensing and signalling functions of the protein. It might also rationalise why avian Cry4a has four tryptophans while cryptochromes from plants have only three.

The function of synapses depends on spatially and temporally controlled molecular interactions between synaptic components that can be described in terms of copy numbers, binding affinities, and diffusion properties. To understand the functional role of a given synaptic protein, it is therefore crucial to quantitatively characterise its biophysical behaviour in its native cellular environment. Single molecule localisation microscopy (SMLM) is ideally suited to obtain quantitative information about synaptic proteins on the nanometre scale. Molecule counting of recombinant proteins tagged with genetically encoded fluorophores offers a means to determine their absolute copy numbers at synapses due to the known stoichiometry of the labelling. As a consequence of its high spatial precision, SMLM also yields accurate quantitative measurements of molecule concentrations. In addition, live imaging of fluorescently tagged proteins at synapses can reveal diffusion dynamics and local binding properties of behaving proteins under normal conditions or during pathological processes. In this perspective, it is argued that the detailed structural information provided by super-resolution imaging can be harnessed to gain new quantitative information about the organisation and dynamics of synaptic components in cellula. To illustrate this point, I discuss the concentration-dependent aggregation of α-synuclein in the axon and the concomitant changes in the dynamic equilibrium of α-synuclein at synapses in quantitative terms.

A model system of highly asymmetric polyelectrolyte with directional short-range attractive interactions was studied by canonical Monte Carlo computer simulations. Comparison of MC data with previously published theoretical results shows good agreement. For moderate values of binding energies, which matches those of molecular docking, a dynamic equilibrium between free and dimerized macroions is observed. Fraction of dimerized macroions depends on macroion concentration, binding energy magnitude, and on the valency of small counterions. Divalent counterions induce an effective attraction between macroions and enhance dimerization. This effect is most notable at low to moderate macroion concentrations., 8 pages, 6 figures

HspB1 is a mammalian sHsp that is ubiquitously expressed in almost all tissues and involved in regulating many vital functions. Although the recent crystal structure of human HspB1 showed that 24 monomers form the oligomeric complex of human HspB1 in a spherical configuration, the molecular architecture of HspB1 is still controversial. In this study, we examined the oligomeric structural change of CgHspB1 by sedimentation velocity analytical ultracentrifugation. At the low temperature of 4 °C, CgHspB1 exists as an 18-mer, probably a trimeric complex of hexamers. It is relatively unstable and partially dissociates into small oligomers, hexamers, and dodecamers. At elevated temperatures, the 24-mer was more stable than the 18-mer. The 24-mer is also in dynamic equilibrium with the dissociated oligomers in the hexameric unit. The hexamer further dissociates to dimers. The disulfide bond between conserved cysteine residues seems to be partly responsible for the stabilization of hexamers. The N-terminal domain is involved in the assembly of dimers and the interaction between hexamers. It is plausible that CgHspB1 expresses a chaperone function in the 24-mer structure.

Rhodamines are the most important class of fluorophores for applications in live-cell fluorescence microscopy. This is mainly because rhodamines exist in a dynamic equilibrium between a fluorescent zwitterion and a non-fluorescent but cell-permeable spirocyclic form. Different imaging applications require different positions of this dynamic equilibrium, which poses a challenge for the design of suitable probes. We describe here how the conversion of the ortho-carboxy moiety of a given rhodamine into substituted acyl benzenesulfonamides and alkylamides permits the systematic tuning of the equilibrium of spirocyclization with unprecedented accuracy and over a large range. This allows to transform the same rhodamine into either a highly fluorogenic and cell-permeable probe for live-cell stimulated emission depletion (STED) microscopy, or into a spontaneously blinking dye for single molecule localization microscopy (SMLM). We used this approach to generate differently colored probes optimized for different labeling systems and imaging applications.

Gram-negative bacteria pose a serious public health concern, primarily due to a higher frequency of antibiotic resistance conferred to them as a result of low permeability of their outer membrane (OM). Antibiotics capable of traversing the OM typically permeate through OM porins; thus, understanding the permeation properties of these porins is instrumental to the development of new antibiotics. A common macroscopic feature of many OM porins is their ability to transition between functionally distinct open and closed states that regulate transport properties and rate. To obtain a molecular basis for these processes, we performed tens of microseconds of molecular dynamics simulations of E. coli OM porin, OmpF. We observed that large-scale motion of the internal loop, L3, leads to widening and narrowing of the pore, suggesting its potential role in gating. Furthermore, Markov state analysis revealed multiple energetically stable conformations of L3 corresponding to open and closed states of the porin. Dynamics between these functional states occurs on the time scale of tens of microseconds and are mediated by the movement of highly conserved acidic residues of L3 to form H-bonds with opposing sides of the barrel wall of the pore. To validate our mechanism, we mutated key residues involved in the gating process that alter the H-bond pattern in the open/closed states and performed additional simulations. These mutations shifted the dynamic equilibrium of the pore towards open or closed states. Complementarily, the mutations favoring the open/closed states lead to increased/decreased accumulation of multiple antibiotics in our whole-cell accumulation assays. Notably, porins containing one of the mutations favoring the closed state has previously been found in antibiotic resistant bacterial strains. Overall, our 180 µs of simulation data (wild type and mutants) with concerted experiments suggests that regulation of the dynamic equilibrium between open and closed states of OM porins could be a mechanism by which Gram-negative bacteria acquire antibiotic resistance.

The cosolvent effect arises from the interaction of cosolute molecules with a protein and alters the equilibrium between native and unfolded states. Denaturants shift the equilibrium toward the latter, while osmolytes stabilize the former. The molecular mechanism whereby cosolutes perturb protein stability is still the subject of considerable debate. Probing the molecular details of the cosolvent effect is experimentally challenging as the interactions are very weak and transient, rendering them invisible to most conventional biophysical techniques. Here, we probe cosolute–protein interactions by means of NMR solvent paramagnetic relaxation enhancement together with a formalism we recently developed to quantitatively describe, at atomic resolution, the energetics and dynamics of cosolute–protein interactions in terms of a concentration normalized equilibrium average of the interspin distance, [Formula: see text] , and an effective correlation time, τ(c). The system studied is the metastable drkN SH3 domain, which exists in dynamic equilibrium between native and unfolded states, thereby permitting us to probe the interactions of cosolutes with both states simultaneously under the same conditions. Two paramagnetic cosolute denaturants were investigated, one neutral and the other negatively charged, differing in the presence of a carboxyamide group versus a carboxylate. Our results demonstrate that attractive cosolute–protein backbone interactions occur largely in the unfolded state and some loop regions in the native state, electrostatic interactions reduce the [Formula: see text] values, and temperature predominantly impacts interactions with the unfolded state. Thus, destabilization of the native state in this instance arises predominantly as a consequence of interactions of the cosolutes with the unfolded state.

Bulk phase chemistry is hardly ever a reasonable approximation to interpret chemical reactivity in compartmentalized systems, because multiphasic systems may alter the course of chemical reactions by modifying the local concentrations and orientations of reactants and by modifying their physical properties (acid-base equilibria, redox potentials, etc.), making them—or inducing them—to react in a selective manner. Exploiting multiphasic systems as beneficial reaction media requires an understanding of their effects on chemical reactivity. Chemical reactions in multiphasic systems follow the same laws as in bulk solution, and the measured or observed rate constant of bimolecular reactions can be expressed, under dynamic equilibrium conditions, in terms of the product of the rate constant and of the concentrations of reactants. In emulsions, reactants distribute between the oil, water, and interfacial regions according to their polarity. However, determining the distributions of reactive components in intact emulsions is arduous because it is physically impossible to separate the interfacial region from the oil and aqueous ones without disrupting the existing equilibria and, therefore, need to be determined in the intact emulsions. The challenge is, thus, to develop models to correctly interpret chemical reactivity. Here, we will review the application of the pseudophase kinetic model to emulsions, which allows us to model chemical reactivity under a variety of experimental conditions and, by carrying out an appropriate kinetic analysis, will provide important kineticparameters. Fundação para a Ciência e a Tecnologia | Ref. UIDB / QUI / 50006/2020 Fundação para a Ciência e a Tecnologia | Ref. POCI-01-0145-FEDER-032492 Fundação para a Ciência e a Tecnologia | Ref. SFRH / BD / 100889/2014 Fundação para a Ciência e a Tecnologia | Ref. PTDC / OCEETA / 32492/2017 Xunta de Galicia | Ref. 10TAL314003PR

Cyanodiarylethene chromophores are able to undergo constitutional exchange via dynamic covalent chemistry (DCC). During this process, the central ethylene bridge of the molecular scaffold can be broken and thereby enables the assembly of a new combination of aryl moieties around the reformed ethylene bridge. The reversible C═C double bond exchange has exemplarily been investigated using α-cyanostilbenes. Establishing a dynamic equilibrium reaction from α-cyanodiarylethene with arylacetonitriles under mild conditions has been the basis to access constitutional libraries of new photoswitches with potentially improved properties. When subject to irradiation with light of adequate wavelength, α-cyanodiarylethenes undergo Z/E isomerization followed by ring-closure. By screening the thus accessible dynamic chromophore libraries using a desired detection wavelength, we could identify specific dithienyl analogues that exhibit three-state photochromism. The combination of dynamic constitutional libraries of functional chromophores in combination with the light-guided screening and selection should lead to more rapid exploration of structural diversity dye chemistry.

The reaction of gold(i) chloride with two molecules of 1,5-diaza-3,7-diphosphacyclooctane derivative causes their reorganization into 16-membered macrocyclic tetraphosphine ligand. The structure of the trinuclear gold(i) complex obtained was confirmed by X-ray analysis. The dynamic equilibrium between dinuclear gold(i) complexes with eight-membered cyclic ligands and the trinuclear gold(i) complex with 16-membered ones has been revealed.

For the first time, 15N NMR data are obtained for a sample of nitric oxide at various temperatures. Spectra have been obtained in the liquid and solid state. In the former, the chemical shift as well as the spin-lattice relaxation time is characterized by the dynamic equilibrium of the dimerization reaction. Only the signal of the (NO)2 dimer is observed, while the paramagnetic NO has strong influences on the NMR parameter. From T1 relaxation and linewidth analysis a range for the correlation time of the exchange between monomer and dimer is obtained. SQUID measurements corroborate the NMR analysis.

The solution of various applied problems usually leads to the need to find answers to purely scientific fundamental questions and discover new phenomena. The article gives examples of such discoveries. It was discovered that flammability of polymeric materials can be decreased by dispersion of a material containing microencapsulated low-boiling flame retardants on exposure to an external fire source. The composition of the Earth’s atmosphere is analyzed in terms of dynamic equilibrium of the processes of oxygen production from forests and the consumption for their combustion during fires. The study of the amazing kinetics of the preparation of polyformaldehyde from formaldehyde and its cyclic trimer, trioxane, was explained, firstly, in the creation of the theory of reversible heterogeneous polymerization of trioxane and led to a fundamentally new, thermodynamic, method of regulating the molecular and supramolecular structure of the polymer. Secondly, on the example of polymerization of formaldehyde, a possible advantage of “diffusion” over “kinetic” modes was discovered. A similar effect was confirmed for the process of sulfuric acid alkylation of high-octane gasoline production.

Summary The twin-ATPase ABCE1 has a vital function in mRNA translation by recycling terminated or stalled ribosomes. As for other functionally distinct ATP-binding cassette (ABC) proteins, the mechanochemical coupling of ATP hydrolysis to conformational changes remains elusive. Here, we use an integrated biophysical approach allowing direct observation of conformational dynamics and ribosome association of ABCE1 at the single-molecule level. Our results from FRET experiments show that the current static two-state model of ABC proteins has to be expanded because the two ATP sites of ABCE1 are in dynamic equilibrium across three distinct conformational states: open, intermediate, and closed. The interaction of ABCE1 with ribosomes influences the conformational dynamics of both ATP sites asymmetrically and creates a complex network of conformational states. Our findings suggest a paradigm shift to redefine the understanding of the mechanochemical coupling in ABC proteins: from structure-based deterministic models to dynamic-based systems., Graphical Abstract, Highlights • Both ATP sites of ABCE1 are in an asymmetric conformational equilibrium • Each ATP site can adopt three functionally distinct conformational states • These equilibria shift during ribosome recycling depending on interaction partners • ATP binding, but not hydrolysis, is required for ribosome splitting, Gouridis et al. delineate the inner workings of ABCE1 by single-molecule FRET, demonstrating that the two asymmetric nucleotide-binding sites functionally and conformationally adopt distinct states during ribosome recycling. Unexpectedly, both sites are found in a dynamic equilibrium of conformational states governed by ribosomes, nucleotides, and release factors.

We report the x-ray crystal structure of intact, full-length human immunoglobulin (IgG4) at 1.8 A resolution. The data for IgG4 (S228P), an antibody targeting the natriuretic peptide receptor A, show a previously unrecognized type of Fab-Fc orientation with a distorted λ-shape in which one Fab-arm is oriented toward the Fc portion. Detailed structural analysis by x-ray crystallography and molecular simulations suggest that this is one of several conformations coexisting in a dynamic equilibrium state. These results were confirmed by small angle x-ray scattering in solution. Furthermore, electron microscopy supported these findings by preserving molecule classes of different conformations. This study fosters our understanding of IgG4 in particular and our appreciation of antibody flexibility in general. Moreover, we give insights into potential biological implications, specifically for the interaction of human anti-natriuretic peptide receptor A IgG4 with the neonatal Fc receptor, Fcγ receptors, and complement-activating C1q by considering conformational flexibility.

Nitromethane dissolved in carbontetrachloride or cyclohexane as inert solvents, exhibits some of its unique chemical properties in such solutions. Spectroscopic evidence reveals that the molecules are found as discrete entities in the concentration range of about 0.05–0.18 M. Beyond this concentration limit the molecules of nitromethane define a smooth but sharp inflexion point as the concentration increases signifying a transition region at which the formation of dimers by head to tail association of two of its molecules begins. The stability of the dimer is supported by ab initio and DFT calculations and its existence is implied by the results of calculated 1H and 13C NMR chemical shifts and confirmed by experimental 1H NMR evidence. In the transition region, only monomers and dimers of nitromethane coexist in dynamic equilibrium. By the end of the turn in the curve of inverse bandwidth against molar concentration of nitromethane, the dimer species start building up a more complex layered structure whose basic units are the dimers of nitromethane, at this point the curve defines a plateau of constant intensity and almost independent of the concentration of nitromethane in solution.

Dynamic covalent chemistry is a new research area based on reversible covalent reactions. In such systems, the interconnected small molecules under dynamic equilibrium served as a responsive entirety, providing the possibility for constitutional selections and optimizations upon internal or external stimuli. When the stimulus is biocatalyst-enzyme, on one hand, the single reversible reaction enables fast racemization of substrates’ enantiomers, leading to highly increased product’s yield and enantiomeric excess (ee) through dynamic kinetic resolution; on the other hand, dynamic combinatorial chemistry can be used for screening of optimal enzyme substrates, with the increased versatility of the dynamic systems, the best fitted substrates can be efficiently obtained, to further achieve information on enzyme’s catalytic activity and active sites, holding broad applications in future biomedical developments.

The self-assembly of virus capsids is a potential target for antivirals due to its importance in the virus lifecycle. Here, we investigate the effect of phenylpropenamide derivatives B-21 and AT-130 on the assembly of hepatitis B virus (HBV) core protein. Phenylpropenamides are widely believed to yield assembly of spherical particles resembling native, empty HBV capsids. Because the details of assembly can be overlooked with ensemble measurements, we performed resistive-pulse measurements on nanofluidic devices with four pores in series to characterize the size distributions of the products in real time. With its single particle sensitivity and compatibility with typical assembly buffers, resistive-pulse sensing is well suited for analyzing virus assembly in vitro. We observed that assembly with B-21 and AT-130 produced a large fraction of partially complete virus particles that may be on-path, off-path, or trapped. For both B-21 and AT-130, capsid assembly was more sensitive to disruption under conditions where the inter-protein association energy was low at lower salt concentrations. Dilution of the reaction solutions led to the rearrangement of the incomplete particles and demonstrated that these large intermediates may be on-path, but are labile, and exist in a frustrated dynamic equilibrium. During capsid assembly, phenylpropenamide molecules modestly increase the association energy of dimers, prevent intermediates from dissociating, and lead to kinetic trapping where the formation of too many capsids has been initiated leading to both empty and incomplete particles.

An electrochemical cell contains three open thermodynamic systems that, in dynamic equilibrium, equalize their electrochemical potentials with that of their surrounding by forming an electric-double-layer-capacitor at the interface of the electrolyte with each of the two electrodes. Since the electrode/electrolyte interfaces are heterojunctions, the electrochemical potentials or Fermi levels of the two materials that contact the electrolyte at the two electrodes determine the voltage of a cell. The voltage is the sum of the voltages of the two interfacial electric-double-layer capacitors at the two electrode/electrolyte interfaces. A theoretical analysis of the thermodynamics that gives a quantitative prediction of the observed voltages in an asymmetric cell with an S8 relay at the positive electrode is provided. In addition, new discharge data and an X-ray photoelectron spectroscopy analysis of the lithium plated on the positive electrode of a discharged cell is presented. Ab initio, DFT methods were used to calculate the band structure and surface-state energies of the crystalline S8 solid sulfur relay. The theoretical exposition of the thermodynamics of the operative driving force of the chemical reactions in an electrochemical cell demonstrate that our initial experimental data and conclusions are valid. Other reported observations of lithium plating on the positive electrode, observations that were neither exploited nor their origins specified, are also cited.

Controlling how, when and where a self-assembly process occurs is essential for the design of the next generation of smart materials. Along this route, enzyme-assisted self-assembly is a powerful tool developed during the last decade. Here we introduce another strategy allowing for spatiotemporal control over peptide self-assemblies. We use a Fmoc-peptide precursor in dynamic equilibrium with its low molecular weight hydrogelator (LMWH) through a reversible disulfide bond. In the absence of proteins, no self-assembly of the hydrogelator is observed. In the presence of proteins, their interactions with the precursor initiate a self-assembly process of the hydrogelator around them. This self-assembly displaces the equilibrium between precursor and LMWH according to Le Chatelier's principle, producing new hydrogelators available to pursue the self-assembly growth. One thus establishes a self-sustaining cycle fuelled by the self-assembly itself until full consumption of the LMWH. For proteins in solutions this process can lead to a supramolecular hydrogel whereas for proteins deposited on a surface, the gel growth is initiated exclusively from the surface. journal article 2019 May 14 2019 03 11 imported

Complex coacervate core micelles (C3Ms) are promising encapsulators for a wide variety of (bio)molecules. To protect and stabilize their cargo, it is essential to control their exchange dynamics. Yet, to date, little is known about the kinetic stability of C3Ms and the dynamic equilibrium of molecular building blocks with micellar species. Here we study the C3M exchange during the initial micellization by using Langevin dynamics simulations. In this way, we show that charge neutral heterocomplexes consisting of multiple building blocks are the primary mediator for exchange. In addition, we show that the kinetic stability of the C3Ms can be tuned not only by the electrostatic interaction but also by the nonelectrostatic attraction between the polyelectrolytes, the polyelectrolyte length ratio, and the overall polyelectrolyte length. These insights offer new rational design guides to aid the development of new C3M encapsulation strategies.

Intrinsically disordered proteins (IDPs) carry out many biological functions. They lack a stable 3D structure and are able to adopt many different conformations in dynamic equilibrium. The interplay between local dynamics and global rearrangements is key for their function. A widely used experimental NMR spectroscopy approach to study long-range contacts in IDPs exploits paramagnetic effects, and 1 H detection experiments are generally used to determine paramagnetic relaxation enhancement (PRE) for amide protons. However, under physiological conditions, exchange broadening hampers the detection of solvent-exposed amide protons, which reduces the content of information available. Herein, we present an experimental approach based on direct carbon detection of PRE that provides improved resolution, reduced sensitivity to exchange broadening, and complementary information derived from the use of different starting polarization sources.

The molecular mechanisms that help to place the division septum in bacteria is of fundamental importance to ensure cell proliferation and maintenance of cell shape and size. The Min protein system, found in many rod-shaped bacteria, is thought to play a major role in division site selection., Division site selection is a vital process to ensure generation of viable offspring. In many rod-shaped bacteria, a dynamic protein system, termed the Min system, acts as a central regulator of division site placement. The Min system is best studied in Escherichia coli, where it shows a remarkable oscillation from pole to pole with a time-averaged density minimum at midcell. Several components of the Min system are conserved in the Gram-positive model organism Bacillus subtilis. However, in B. subtilis, it is commonly believed that the system forms a stationary bipolar gradient from the cell poles to midcell. Here, we show that the Min system of B. subtilis localizes dynamically to active sites of division, often organized in clusters. We provide physical modeling using measured diffusion constants that describe the observed enrichment of the Min system at the septum. Mathematical modeling suggests that the observed localization pattern of Min proteins corresponds to a dynamic equilibrium state. Our data provide evidence for the importance of ongoing septation for the Min dynamics, consistent with a major role of the Min system in controlling active division sites but not cell pole areas.

The noncanonical heme oxygenase MhuD from Mycobacterium tuberculosis binds a heme substrate that adopts a dynamic equilibrium between planar and out-of-plane ruffled conformations. MhuD degrades this substrate to an unusual mycobilin product via successive monooxygenation and dioxygenation reactions. This article establishes a causal relationship between heme substrate dynamics and MhuD-catalyzed heme degradation, resulting in a refined enzymatic mechanism. UV/vis absorption (Abs) and electro-spray ionization mass spectrometry (ESI-MS) data demonstrated that a second-sphere substitution favoring the population of the ruffled heme conformation changed the rate-limiting step of the reaction, resulting in a measurable buildup of the monooxygenated meso-hydroxyheme intermediate. In addition, UV/vis Abs and ESI-MS data for a second-sphere variant that favored the planar substrate conformation showed that this change altered the enzymatic mechanism resulting in an α-biliverdin product. Single-turnover kinetic analyses for three MhuD variants revealed that the rate of heme monooxygenation depends upon the population of the ruffled substrate conformation. These kinetic analyses also revealed that the rate of meso-hydroxyheme dioxygenation by MhuD depends upon the population of the planar substrate conformation. Thus, the ruffled heme conformation supports rapid heme monooxygenation by MhuD, but further oxygenation to the mycobilin product is inhibited. In contrast, the planar substrate conformation exhibits altered heme monooxygenation regiospecificity followed by rapid oxygenation of meso-hydroxyheme. Altogether, these data yielded a refined enzymatic mechanism for MhuD where access to both substrate conformations is needed for rapid incorporation of three oxygen atoms into heme yielding mycobilin.

SUMMARYTemporal control of inflammation is critical to avoid pathological developments, and is largely defined through the differential stabilities of mRNAs. While TTP-directed mRNA deadenylation is known to destabilize ARE-containing mRNAs, this mechanism alone cannot explain the variety of mRNA expression kinetics observed during inflammation resolution. Here we show that inflammation resolution requires CPEB4 expression, in vitro and in vivo. Our results identify that CPEB4-directed polyadenylation and TTP-mediated deadenylation compete during the resolutive phase of the LPS response to uncouple the degradation of pro-inflammatory mRNAs from the sustained expression of anti-inflammatory mRNAs. The outcome of this equilibrium is quantitatively defined by the relative number of CPEs and AREs in each mRNA, and further shaped by the coordinated regulation by the MAPK signalling pathway of the levels and activities of their trans-acting factors, CPEB4 and TTP. Altogether, we describe a temporal- and transcript-specific regulatory network controlling the extent of the inflammatory response.

s Conventional synthesis of the phthalazine has already allowed affording the phthalazin-1-one phthalazin-1-ol dynamic equilibrium that decreases the anticancer activity due to diminishing the concentration of the phthalazin-1-ol product. Nowadays, pure phthalazin-1-ol (5) can be gaining by using green microwave tools that increase the power of the phthalazine nucleus as an anticancer drug. A microscopic thermal kinetic parameter like activation energy and the pre-exponential factor of the chemical plasma organic reactions affording pure phthalazin-1-ol (5) is calculated by using DFT simulation is obtained. Then we fed these parameters into the exact Arrhenius model to evaluate the distribution of chemical equilibrium conditions for producing phthalazin-1-ol. The proposed novel models that matching between microscopic and macroscopic show that the thermal stability of the equivalent temperature of phthalazin-1-ol is more stable than phthalazinone-1-one (4) in case of using plasma organic effect (green microwave) at 485 K. The structures of the prepared compounds were explained by physical and spectral data like FT-IR, 1H-NMR. Moreover, the theoretical calculations of Gibbs entropy of the phase transfer confirmed the equilibrium state of phthalazin-1-ol with the experimental result is achieved. Briefly, we introduce a good study for obtaining more stable phthalazin-1-ol isomer by using a green microwave method which is considered as good anticancer reagents of phenolic group (OH) and p-propenyl-anisole precursor as anise oil analogous., Efficient green microwave synthesis, Phthalazin-1(2H)-ol, Arrhenius model, DFT simulation, Anticancer HepG2, HCT-116 and MCF-7.

Small heat shock proteins (sHSPs) are ATP-independent molecular chaperones with low molecular weight that prevent the aggregation of proteins during stress conditions and maintain protein homeostasis in the cell. sHSPs exist in dynamic equilibrium as a mixture of oligomers of various sizes with a constant exchange of subunits between them. Many sHSPs form cage-like assemblies that may dissociate into smaller oligomers during stress conditions. We carried out the functional and structural characterization of a small heat shock protein, HSP18.5, from Entamoeba histolytica (EhHSP18.5). It showed a pH-dependent change in its oligomeric state, which varied from a tetramer to larger than 48-mer. EhHSP18.5 protected Nde I and lysozyme substrates from temperature and chemical stresses, respectively. The crystal structure of EhHSP18.5 was determined at a resolution of 3.28 a in C2221 cell with four subunits in the asymmetric unit forming two non-metazoan sHSP-type dimers. Unlike the reported cage-like structures, EhHSP18.5 formed a network of linear chains of molecules in the crystal. Instead of a single [IV]-X-[IV] motif, EhHSP18.5 has two overlapping I/V-X-I/V sequences at the C-terminus giving rise to novel interactions between the dimers. Negative staining Electron Microscopy images of EhHSP18.5 showed the presence of multiple oligomers: closed structures of various sizes and long tube-like structures. This article is protected by copyright. All rights reserved.

Since the discovery of muscle in the 19th century, myosins as molecular motors have been extensively studied. However, in the last decade, a new functional super-relaxed (SRX) state of myosin has been discovered, which has a 10-fold slower ATP turnover rate than the already-known non-actin-bound, disordered relaxed (DRX) state. These two states are in dynamic equilibrium under resting muscle conditions and are thought to be significant contributors to adaptive thermogenesis in skeletal muscle and can act as a reserve pool that may be recruited when there is a sustained demand for increased cardiac muscle power. This report provides an evolutionary perspective of how striated muscle contraction is regulated by modulating this myosin DRX↔SRX state equilibrium. We further discuss this equilibrium with respect to different physiological and pathophysiological perturbations, including insults causing hypertrophic cardiomyopathy, and small-molecule effectors that modulate muscle contractility in diseased pathology.

A copper(I) complex [CuCl{k1(P)-1a}{k2(P,N)-1a}] (1a = 2,5-bis(2-pyridyl)-1-phenylphosphole) with pseudo tetrahedral geometry was synthesized. In solution, 1a displays a hemilabile behaviour leading to a dynamic equilibrium between four and three-coordinate specie. Its catalytic potential was tested in synthesis of propargylamines and 1,2,3-triazoles via three-component reactions. Experimental results discussed on base to DFT calculations.