Molecular Kinetics Research Articles

Modeling of high-speed, methane–air, turbulent combustion, Part I: One-dimensional turbulence modeling with comparison to DNS

The ability of the one-dimensional turbulence (ODT) model to serve as a surrogate direct numerical simulation (DNS) is assessed for highly turbulent flames. The ODT model is applied to freely propagating premixed methane–air flames at Karlovitz numbers 10, 102, 103, and 104, and results are compared with DNS. The ODT model solves the conservation equations for momentum, energy, and species on a one-dimensional domain, which corresponds to a streamwise line of sight spanning the DNS domain. The effects of turbulent advection are modeled via a stochastic process, in which the Kolmogorov and reactive length and time scales are explicitly resolved. Molecular transport and chemical kinetics are concurrently advanced in time. Both the ODT and DNS simulations use a 21-species skeletal chemical model for methane combustion. The accuracy of the ODT model is assessed by comparing its predictions of several key characteristics of the flames for each Karlovitz number tested, including the turbulent flame speed and width and the joint probability density functions (jPDFs) of major and selected minor species as well as the heat release rate conditioned on temperature with the results of DNS under comparable conditions. The ODT model is shown to yield qualitative and quantitative agreement with the DNS data for most of the above flame characteristics. Discrepancies are observed primarily for the jPDFs of several minor species examined. Overall, the ODT approach is shown to be an effective surrogate of DNS, potentially useful for guiding chemical reaction model reduction and for assessing the sensitivities of the flame structure and the burning rate to chemistry under highly turbulent conditions.Novelty and Significance:The direct numerical simulations (DNS) of premixed turbulent methane–air flames presented in this work span a uniquely wide range of turbulent intensities, from relatively modest corresponding to Karlovitz number Ka=10 to ultra-high intensities at Ka=104. This represents virtually the entire range of turbulent intensities that could be encountered in any realistic situation. This is also the first time that such a wide range of conditions is probed for methane in high-fidelity, fully resolved simulations, which use a fully compressible set of flow equations. The one-dimensional turbulence (ODT) model utilizes the same forcing that is present in the DNS enabling a direct comparison between the ODT and DNS. The results show that ODT captures the key features of the DNS results. ODT is shown to be an effective surrogate for DNS and may be useful in guiding chemical reaction model reduction, where many simulations are required.

Molecular kinetics of transcription and chromatin mobility during embryonic development

Molecular kinetics of transcription and chromatin mobility during embryonic development

Molecular kinetics of polycomb body formation during development

Molecular kinetics of polycomb body formation during development

Molecular kinetics of transcription regulation during embryonic development

Molecular kinetics of transcription regulation during embryonic development

Reaction coordinate flows for model reduction of molecular kinetics.

In this work, we introduce a flow based machine learning approach called reaction coordinate (RC) flow for the discovery of low-dimensional kinetic models of molecular systems. The RC flow utilizes a normalizing flow to design the coordinate transformation and a Brownian dynamics model to approximate the kinetics of RC, where all model parameters can be estimated in a data-driven manner. In contrast to existing model reduction methods for molecular kinetics, RC flow offers a trainable and tractable model of reduced kinetics in continuous time and space due to the invertibility of the normalizing flow. Furthermore, the Brownian dynamics-based reduced kinetic model investigated in this work yields a readily discernible representation of metastable states within the phase space of the molecular system. Numerical experiments demonstrate how effectively the proposed method discovers interpretable and accurate low-dimensional representations of given full-state kinetics from simulations.

Monitoring the response of a model protocell to dye and surfactant molecules through second harmonic generation and fluorescence imaging.

Probing the interaction between molecules and protocells is crucial for understanding the passive transport of functional molecules in and out of artificial and real cells. Second-harmonic generation (SHG) has been proven to be a powerful method for analyzing the adsorption and cross-membrane transport of molecules on lipid bilayers. In this study, we used SHG and two-photon fluorescence (TPF) imaging to study the interaction of charged dye molecules (D289) with a lipid vesicle. Unexpectedly, it was observed that the transport of D289 at a relatively high concentration is not as efficient as that at a lower dye concentration. Periodic shrinking of the model protocell and discharging of D289 out from the vesicle were revealed by combined analyses of SHG and TPF images. The response of the vesicle to a surfactant was also analyzed with D289 as a probe. This work demonstrates that the combined SHG and TPF imaging method is a unique approach that can provide detailed information on the interaction of molecules and lipids (both morphology and molecular kinetics). Determining these subtle interfacial kinetics in molecules is important for understanding the mechanism of many biophysical processes occurring on lipids.

Understanding the application of covalent adaptable networks in self-repair materials based on molecular simulation.

Covalent adaptable networks (CANs) are widely used in the field of self-repair materials. They are a group of covalently cross-linked associative polymers that undergo reversible chemical reactions, and can be further divided into dissociative CANs (Diss-CANs) and associative CANs (Asso-CANs). Self-repair refers to the ability of a material to repair itself without external intervention, and can be classified into self-adhesion and self-healing according to the utilization of open stickers. Unlike conventional materials, the viscoelastic properties of CANs are influenced by both the molecular structure and reaction kinetics, ultimately affecting their repair performance. To gain deeper insight into the repair mechanism of CANs, we conducted simulations by using the hybrid MC/MD algorithm, as previously proposed in our research. Interestingly, we observed a significant correlation between reaction kinetics and repair behavior. Asso-CANs exhibited strong mechanical strength and high creep resistance, rendering them suitable as self-adhesion materials. On the other hand, Diss-CANs formed open stickers that facilitated local relaxation, aligning perfectly with self-healing processes. Moreover, the introduction of crosslinkers in the form of small molecules enhanced the repair efficiency. Theoretically, it was found that the repair timescale of Asso-CANs is slower than that of Diss-CANs with identical molecular structures. Our study not only clarifies the similarities and differences between Diss-CANs and Asso-CANs in terms of their self-repairing capabilities, but more importantly, it provides valuable insights guiding the effective utilization of CANs in the development of self-repair materials.

In silico screening and characterization, inhibition mechanism on ACE, and stability of antihypertensive peptides with Zn-chelating capacity identified from millet bran albumin hydrolysates

To obtain Angiotensin-I-Converting Enzyme (ACE) inhibition peptides with Zn-chelating capacity, millet bran albumin hydrolysates (MBAH) were subjected to Sephadex G-15 gel and reverse phase-high liquid performance chromatography, and UPLC-ESI-MS/MS analysis. Five oligopeptides including Val-Gly-Ser-Asp-Gly-Leu (VGSDGL), Thr-Gly-His-Gly-Val-Ala (TGHGVA), Gly-Cys-His-His-Tyr (GCHHY), Leu-Val-Glu-Ala-Val-Pro-Arg-Gly (LVEAVPRG) and Val-Leu-Ala-Gln-Glu-Glu (VLAQEE) were identified in MBAH. Of these, only pentapeptide GCHHY showed both ACE-inhibitory activity (IC50: 134.78 μmol/L) and Zn-chelating capacity (14.16 mg/g). Molecular docking and inhibition kinetics showed that GCHHY was a competitive inhibitor of ACE, because it could bind with Lys511 of ACE which belongs to the central S2 pocket. Moreover, GCHHY can affect zinc tetrahedral coordination in ACE through binding with Glu411 and His383. The sulfhydryl, amino and carboxyl groups of GCHHY can bind with zinc ions. Under the gastrointestinal digestion, the ACE-inhibitory activity of GCHHY was relatively stable, and the zinc solubility of GCHHY-Zn complexes was more stable than zinc sulfate (P < 0.05). In addition, both GCHHY and GCHHY-Zn complexes lowered the diastolic blood pressure and systolic blood pressure of spontaneous hypertensive rats at dose of 50–200 mg/kg body weight. These results suggested the potential applications of millet albumin peptides as ingredients for antihypertension or zinc fortification.

2-Dimensional Materials for Performance Enhancement of Surface Plasmon Resonance Biosensor: Review Paper

Surface plasmon resonance (SPR)--based biosensors compete and excel among optical biosensors because of exceptional features such as high sensitivity, label-free, and real-time measurement, allowing the observation of molecular binding kinetics. In SPR biosensors and other biosensor techniques, surface functionalization and bioreceptor attachment are effective strategies to improve sensor performance. The application of an appropriate immobilization matrix for the bioreceptor is an essential step in maximizing the absorption of the bioreceptor on the sensor surface, thereby improving a specific target-sensor interaction. Furthermore, the materials should provide excellent optical properties to enhance the response signal. The high surface-to-volume ratio and high optical absorption of 2D materials qualify these requirements, thus promising advancements for SPR biosensors. This article reviews the recent SPR biosensor study with the use of the 2D materials family to improve the sensor performance, including graphene, transition metal dichalcogenides (TMDCs), MXene, black phosphorus (BP), perovskite, and boron nitride (BN). The materials properties and enhancement mechanisms of different 2D materials are discussed comprehensively. This review was expected to provide a future perspective and design approach for 2D materials-based SPR biosensors.

A theoretical kinetic study of 1-butyne, 2-butyne, and 3-methyl-1-butyne combustion

Propargylic radicals are an essential component in molecular weight growth kinetics and can react to form polycyclic aromatic hydrocarbons and soot. To establish rate rules for propargylic radicals, a total of 16 H-atom abstraction reactions of three alkynes, namely 1-butyne (1-C4H6), 2-butyne (2-C4H6), and 3-methyl-1-butyne (C5H8), were calculated using high-level quantum chemistry, in which four active radicals including Ḣ, ȮH, ĊH3, and HȮ2 were involved. Considering the completeness of the establishment of rate rules, the H-atom abstraction sites have included the primary and secondary site of 1-C4H6, primary site of 2-C4H6, and tertiary site of C5H8. The M06–2X/6–311++G(d,p) level of density function theory was used for the geometry optimization, vibrational frequency, and dihedral scan calculations. Single point energy calculations were carried out at the CCSD/cc-pVXZ (X = T, Q) level of coupled cluster theory. The rate coefficients for all of the abstraction reactions and the thermochemical quantities of 1-C4H6, 2-C4H6, and C5H8 and their corresponding radical products were calculated. The results indicate that H-atom abstraction by ȮH radicals has the fastest reaction rates for all three species. Moreover, abstraction from the tertiary site on C5H8 is the fastest, followed by abstraction of secondary hydrogen atoms on 1-C4H6 and primary hydrogen atoms on 2-C4H6, while abstraction of primary hydrogen atoms on 1-C4H6 are the slowest. NUIGMech1.3 (mechanism of version 1.3 proposed by National University of Ireland, Galway) has been updated based on our calculations, and ignition delay times (IDTs) were predicted using the updated mechanism. The predicted IDTs gave better agreement with the experiment data at pressures of 1, 30 and 50 bar. Sensitivity analyses were performed to understand observed model predicted differences at low to intermediate temperatures (700–1000 K) at 10 bar. The results show that the reactions 1-C4H6/2-C4H6 + HȮ2 and HȮ2 + HȮ2<=> H2O2 + O2 have a significant effect on promoting and inhibiting reactivity, respectively. Further Flux analyses show that the H-atom abstraction from 1-C4H6 and 2-C4H6 by ȮH radical is a dominant channel in changing branching ratios.

Continuous therapy response references for BCR::ABL1 monitoring in pediatric chronic myeloid leukemia

Response to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML) is monitored by quantification of BCR::ABL1 transcript levels. Milestones for assessing optimal treatment response have been defined in adult CML patients and are applied to children and adolescents although it is questionable whether transferability to pediatric patients is appropriate regarding genetic and clinical differences. Therefore, we analyzed the molecular response kinetics to TKI therapy in 129 pediatric CML patients and investigated whether response assessment based on continuous references can support an early individual therapy adjustment. We applied a moving quantiles approach to establish a high-resolution response target curve and contrasted the median responses in all patients with the median of the ideal target curve obtained from a subgroup of optimal responders. The high-resolution response target curve of the optimal responder group presents a valuable tool for continuous therapy monitoring of individual pediatric CML patients in addition to the fixed milestones. By further comparing BCR::ABL1 transcript levels with BCR::ABL1 fusion gene copy numbers, it is also possible to model the differential dynamics of BCR::ABL1 expression and cell number under therapy. The developed methodology can be transferred to other biomarkers for continuous therapy monitoring.

A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation

Cell cycle transitions result from global changes in protein phosphorylation states triggered by cyclin-dependent kinases (CDKs). To understand how this complexity produces an ordered and rapid cellular reorganisation, we generated a high-resolution map of changing phosphosites throughout unperturbed early cell cycles in single Xenopus embryos, derived the emergent principles through systems biology analysis, and tested them by biophysical modelling and biochemical experiments. We found that most dynamic phosphosites share two key characteristics: they occur on highly disordered proteins that localise to membraneless organelles, and are CDK targets. Furthermore, CDK-mediated multisite phosphorylation can switch homotypic interactions of such proteins between favourable and inhibitory modes for biomolecular condensate formation. These results provide insight into the molecular mechanisms and kinetics of mitotic cellular reorganisation.

Biodegradation of fipronil: molecular characterization, degradation kinetics, and metabolites.

Fipronil (C12H4Cl2F6N4OS) is a commonly used insecticide effective against numerous insects and pests. Its immense application poses harmful effects on various non-target organisms as well. Therefore, searching the effective methods for the degradation of fipronil is imperative and logical. In this study, fipronil-degrading bacterial species are isolated and characterized from diverse environments using a culture-dependent method followed by 16S rRNA gene sequencing. Phylogenetic analysis showed the homology of organisms with Acinetobacter sp., Streptomyces sp., Pseudomonas sp., Agrobacterium sp., Rhodococcus sp., Kocuria sp., Priestia sp., Bacillus sp., Aeromonas sp., and Pantoea sp. The bacterial degradation potential for fipronil was analyzed through high-performance liquid chromatography(HPLC). Incubation-based degradation studies revealed that Pseudomonas sp. and Rhodococcus sp. were found to be the most potent isolates that degraded fipronil at 100mg L-1 concentration, with removal efficiencies of 85.9 and 83.6%, respectively. Kinetic parameter studies, following the Michaelis-Menten model, also revealed the high degradation efficiency of these isolates. Gas chromatography-mass spectrometry (GC-MS) analysis revealed fipronil sulfide, benzaldehyde, (phenyl methylene) hydrazone, isomenthone, etc., as major metabolites of fipronil degradation. Overall investigation suggests that native bacterial species isolated from the contaminated environments could be efficiently utilized for the biodegradation of fipronil. The outcome derived from this study has immense significance in formulating an approach for bioremediation of fipronil-contaminated surroundings.

Tethered particle motion of the adaptation enzyme CheR in bacterial chemotaxis

Bacteria perform chemotactic adaptation by sequential modification of multiple modifiable sites on chemoreceptors through stochastic action of tethered adaptation enzymes (CheR and CheB). To study the molecular kinetics of this process, we measured the response to different concentrations of MeAsp for the Tar-only Escherichia coli strain. We found a strong dependence of the methylation rate on the methylation level and established a new mechanism of adaptation kinetics due to tethered particle motion of the methylation enzyme CheR. Experiments with various lengths of the C-terminal flexible chain in the Tar receptor further validated this mechanism. The tethered particle motion resulted in a CheR concentration gradient that ensures encounter-rate matching of the sequential modifiable sites. An analytical model of multisite catalytic reaction showed that this enables robustness of methylation to fluctuations in receptor activity or cell-to-cell variations in the expression of adaptation enzymes and reduces the variation in methylation level among individual receptors.

Combined SPT and FCS methods reveal a mechanism of RNAP II oversampling in cell nuclei

Gene expression orchestration is a key question in fundamental and applied research. Different models for transcription regulation were proposed, yet the dynamic regulation of RNA polymerase II (RNAP II) activity remains a matter of debate. To improve our knowledge of this topic, we investigated RNAP II motility in eukaryotic cells by combining single particle tracking (SPT) and fluorescence correlation spectroscopy (FCS) techniques, to take advantage of their different sensitivities in order to analyze together slow and fast molecular movements. Thanks to calibrated samples, we developed a benchmark for quantitative analysis of molecular dynamics, to eliminate the main potential instrumental biases. We applied this workflow to study the diffusion of RPB1, the catalytic subunit of RNAP II. By a cross-analysis of FCS and SPT, we could highlight different RPB1 motility states and identifyed a stationary state, a slow diffusion state, and two different modes of subdiffusion. Interestingly, our analysis also unveiled the oversampling by RPB1 of nuclear subdomains. Based on these data, we propose a novel model of spatio-temporal transcription regulation. Altogether, our results highlight the importance of combining microscopy approaches at different time scales to get a full insight into the real complexity of molecular kinetics in cells.

Enrichment, analysis, identification and mechanism of antioxidant components in Toona sinensis

• Toona sinensis has strong antioxidant activity. • Liquid-liquid-refining extraction was developed to enrich antioxidants from extract. • Pentagalloyl glucose and ethyl gallate were the main antioxidants. • Single electron transfer followed by proton transfer is main antioxidant mechanism. The tender leaves of Toona sinensis not only taste delicious, but also have a wide range of biological activities, including strong antioxidant activity. In this study, a method based on liquid-liquid-refining extraction and bioassay-guided separation were established and developed for enrichment, analysis and identification of antioxidant components in T. sinensis . Two main antioxidants, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) and ethyl gallate (EG) with strong antioxidant capacity were responsible for the antioxidant activity of T. sinensis . The EC 50 of EG scavenging ABTS· + and DPPH· were 4.46 ± 0.05 μg/mL and 7.61 ± 0.13 μg/mL, and the EC 50 of PGG were 12.90 ± 0.16 μg/mL and 16.29 ± 0.20 μg/mL. The thermodynamic parameters of various pathways indicated that single electron transfer followed by proton transfer (SET-PT) was the main antioxidant mechanism of PGG and EG. Furthermore, the results of frontier molecular orbital theory and reaction kinetics showed that PGG had low energy gap and reaction energy barrier, which was the fundamental reason why its antioxidant activity was better than EG. Graphical Abstract. .

(Energy Technology Division Graduate Student Award sponsored by BioLogic) Probing and Engineering Electrode-Electrolyte Interfaces in Electrochemical Energy Storage and Conversion

Climate change demands the development of clean energy technologies, where rechargeable batteries and fuel cells promise a bright future by integrating with solar or wind energy. Li-ion batteries and fuel cells also play essential roles in electrifying transportation in replacement of internal combustion engines. Central to these electrochemical systems is the electrode-electrolyte interface, where (electro)chemical surface reactions or intercalation reactions occur, and its thermodynamic and kinetic properties determine the energy density, power density, and lifetime of the electrochemical devices. However, the molecular structures at the interface and how they promote or suppress the desired reactions remain unclear, hindering the rational design of electrode-electrolyte interfaces to improve the performance of electrochemical devices.This talk focuses on the fundamental understanding of the interfacial (electro)chemical reaction mechanisms at the molecular level and charges transfer kinetics at the electrified interfaces. First, an in situ Fourier-transform infrared spectroscopy (FTIR) method was developed to examine the parasitic reactions between carbonate electrolytes and lithium nickel, manganese and cobalt oxides (NMC) in Li-ion batteries, and unique evidence for dehydrogenation reactions on Ni-rich NMC was revealed, which accounted for interface impedance build-up and battery capacity fading. Based on the proposed mechanism, strategies based on electrolyte non-covalent interactions were demonstrated to improve battery lifetime. In the second part of the talk, the research extended in situ FTIR characterization and electrolyte engineering to electrocatalytic reactions central to fuel cell technologies. An interfacial layer of protic ionic liquids with different acid dissociation constants were found to enhance the oxygen-reduction reaction (ORR), attributed to strengthened hydrogen bonding between ORR products and ionic liquids, revealed by in situ surface-enhanced infrared absorption spectroscopy and density functional theory (DFT) calculations. For the hydrogen evolution reaction (HER), similarly, promoting hydrogen bonding between interfacial water molecules also facilitated proton-coupled electron transfer kinetics, resulting in favorable HER in controllable organic confinements. Finally, this talk will introduce fundamental, theoretical aspects of charge transfer processes at the electrode-electrolyte interface - the kinetic mechanism for ion intercalation. Experimental evidence from a charge-adjusted electrochemical method showed that Li-ion intercalation occurs by coupled ion-electron transfer (CIET), which governs the current-dependent maximum capacity and power density of intercalation batteries. these research efforts have laid a solid foundation for the rational design of electrochemical interfaces employing the physical chemistry of electrodes and electrolytes, for next-generation electrochemical storage devices with improved energy and power density and cycle life.

The physicochemical behavior of temozolomide stabilized on folic acid−targeted−gold−thiol modified surface via covalent conjugation towards cancer cells

Conjugation via covalent bonding on nanocarriers is an effective strategy to stabilize drugs and prodrugs, improve their efficiency and decrease their side effects. In this study, temozolomide (TMZ) is used as a prodrug and stabilized via covalent conjugation on folic acid−targeted−gold−thiol modified surface, and then, the physicochemical behavior of the integrated system towards cancer cells is studied by surface techniques, votammetric methods, electrochemical impedance spectroscopy (EIS), and quartz crystal microbalance (QCM). The voltammetric and ATR−FTIR studies revealed that the conjugated TMZ is stable at least for 48 h. The adsorption behavior of A2780 cancer cells onto the system is well described by Freundlich adsorption isotherm with adsorption capacity of 50.11 and adsorption intensity of 1/n = 0.15. The process is controlled by a first order kinetic model with rate constant of 0.036 ± 0.002 min−1 and t1/2 of 18 ± 1 min. To our knowledge, this is the first time that the physicochemical behavior of the TMZ prodrug integrated onto Au−thiol SAM nanostructures is studied by EIS and QCM concerning cancer cells. The results of this research are noteworthy and can improve our physicochemical insights into anticancer drugs in conjunction with gold targeted nanocarriers, regarding the stability of prodrugs, mixed molecular nanostructures, adsorption kinetics and isotherms for sensing and capture of cancer cells.

Efficient approximation of molecular kinetics using random Fourier features.

Slow kinetic processes in molecular systems can be analyzed by computing the dominant eigenpairs of the Koopman operator or its generator. In this context, the Variational Approach to Markov Processes (VAMP) provides a rigorous way of discerning the quality of different approximate models. Kernel methods have been shown to provide accurate and robust estimates for slow kinetic processes, but they are sensitive to hyper-parameter selection and require the solution of large-scale generalized eigenvalue problems, which can easily become computationally demanding for large data sizes. In this contribution, we employ a stochastic approximation of the kernel based on random Fourier features (RFFs) to derive a small-scale dual eigenvalue problem that can be easily solved. We provide an interpretation of this procedure in terms of a finite, randomly generated basis set. By combining the RFF approach and model selection by means of the VAMP score, we show that kernel parameters can be efficiently tuned and accurate estimates of slow molecular kinetics can be obtained for several benchmarking systems, such as deca alanine and the NTL9 protein.

Temperature-dependent determination of NO2 dimerization reaction based on dual-comb spectroscopy.

Dimerization reactions play a critical role in various fields of research, including cell biology, biomedicine, and chemistry. In particular, the dimerization reaction of 2NO2⇌N2O4 has been extensively applied in pollution control and raw material preparation. Spectroscopy, as a powerful tool for investigating molecular structures and reaction kinetics, has been increasingly employed to study dimerization reactions in recent years. In this study, we successfully demonstrated the application of dual-comb spectroscopy (DCS) to analyze NO2 dimerization reactions, making the first report on the application of this technique in this context. Parallel measurements of NO2 and N2O4 fingerprints spectra with high resolution at 3000 cm-1 was performed, benefiting from the unprecedented broadband and high-precision capability of DCS. The absorption cross-sections of N2O4 from 296 to 343 K was obtained from the measured spectra, which contributes to further research on the molecular spectrum of N2O4. These results demonstrate the potential of DCS for studying the dimerization reaction mechanism.