Conformation Of Molecule Research Articles

A perspective on ToF-SIMS analysis of biosensor interfaces: Controlling and optimizing multi-molecular composition, immobilization through bioprinting, molecular orientation

The biosensor interface is the heart of biosensing devices and point-of-need platforms. Analyte detection relies on biosensor surface modifications with different molecules (specific binding molecules, blocking molecules, etc.), accomplished following multi-step functionalization and assay procedures, but discrimination of these molecules is not provided by biosensor response. Mass fabrication of biosensors integrated on a chip is facilitated by spatially-selective functionalization through printing of probe molecules, but the resulting multi-molecular distributions are not readily available. Assay efficiency is determined by the orientation and conformation of probe molecules on biosensor surface, but they are rarely determined during assay development. Above challenges in biosensor functionalization and assay can be solved by microanalysis and chemical imaging provided by Time-of-Flight Secondary Ion Mass Spectrometry. This perspective article shows that biosensor surface modifications can be compared with ToF-SIMS not only to determine but also to optimize multi-molecular composition, bioprinting-based immobilization and molecular orientation. These features are controlled through relevant surface phenomena of adsorption and desorption or droplet evaporation as revealed by ToF-SIMS data. The paper highlights the advantages of molecular discrimination with ToF-SIMS, such as accurate characterization of molecular composition that cannot be deduced only by biosensor response, verification of applied biofunctionalization protocol efficiency, and assay optimization with respect to probe immobilization conditions. Finally, application of ToF-SIMS imaging to biomolecules printed into microarrays, biosensors’ arrays or separate biosensor’s components on a chip are presented, with the printed domains comparable, wider or narrower than the nominal diameter of the printing pin. We hope that the reviewed experimental developments could be an inspiration for future research as to how TOF-SIMS analysis methods could assist in our understanding of complex phenomena taking place onto a surface.

Water in the crystal structure of NaBiO3-based phase: A spectroscopical insight

Water embedded in the crystal structure of a solid hydrate may affect the functional properties of the material. A decisive step towards understanding the role of water in the restricted geometry is to unravel the arrangement and dynamics of water molecules. The paper attacks this issue using the example of NaBiO3–based material containing at ambient conditions a mixture of dehydrated NaBiO3 and hydrated NaBiO3⋅nH2O phase, with the latter being predominant. Inelastic neutron scattering and infrared spectroscopy are applied to explore the vibrations of water molecules for the hydrated phase in the initial state and during the release of water upon heating that eventually leads to a complete transformation to the dehydrated phase. The major peaks in the infrared spectra were assigned, particularly with the help of deuteration. Dynamic interaction of structurally equivalent water molecules was revealed from the analysis of water bending modes in infrared and Raman spectra. The change in the conformation of water molecules is discussed, as well as the deformation of matrix bonds during sample dehydration.

Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

Investigation the influences of water-extractable and water-unextractable arabinoxylan on the quality of whole wheat you-tiao and its mechanism

This research aimed to investigate the effects of water-extractable arabinoxylan (WEAX) and water-unextractable arabinoxylan (WUAX) on the quality of you-tiao. In this work, the interactions between different amounts of AX and wheat gluten were extensively evaluated during frying treatment. The results showed that WEAX impaired the surface hydrophobicity of gluten and improved its solubility, while WUAX had the opposite effect. The fluorescence spectra revealed that WEAX and WUAX changed the conformation of gluten molecules. Besides, chemical interaction measurement indicated that WEAX and WUAX prevented the formation of partial disulfide bonds and inhibited the thermal aggregation of gluten proteins. In summary, the results indicated that WEAX partly improved the properties of you-tiao. Meanwhile, WUAX reduced the dough's oil content and specific volume, resulting in you-tiao with poor quality.

Poly-L-Arginine Molecule Properties in Simple Electrolytes: Molecular Dynamic Modeling and Experiments.

Physicochemical properties of poly-L-arginine (P-Arg) molecules in NaCl solutions were determined by molecular dynamics (MD) modeling and various experimental techniques. Primarily, the molecule conformations, the monomer length and the chain diameter were theoretically calculated. These results were used to interpret experimental data, which comprised the molecule secondary structure, the diffusion coefficient, the hydrodynamic diameter and the electrophoretic mobility determined at various ionic strengths and pHs. Using these data, the electrokinetic charge and the effective ionization degree of P-Arg molecules were determined. In addition, the dynamic viscosity measurements for dilute P-Arg solutions enabledto determine the molecule intrinsic viscosity, which was equal to 500 and 90 for ionic strength of 10−5 and 0.15 M, respectively. This confirmed that P-Arg molecules assumed extended conformations and approached the slender body limit at the low range of ionic strength. The experimental data were also used to determine the molecule length and the chain diameter, which agreed with theoretical predictions. Exploiting these results, a robust method for determining the molar mass of P-Arg samples, the hydrodynamic diameter, the radius of gyration and the sedimentation coefficient was proposed.

Understanding the Interactions between Triolein and Cosolvent Binary Mixtures Using Molecular Dynamics Simulations

Biodiesel is one of the emerging renewable sources of energy to replace fossil-fuel-based resources. It is produced by a transesterification reaction in which a triglyceride reacts with methanol in the presence of a catalyst. The reaction is slow because of the low solubility of methanol in triglycerides, which results in low concentrations of methanol available to react with triglyceride. To speed up the reaction, cosolvents are added to create a single phase which helps to improve the concentration of methanol in the triglyceride phase. In this study, molecular dynamics simulations are used to help understand the role of cosolvents in the solvation of triglyceride (triolein). Six binary mixtures of triolein/cosolvent were used to study the solvation of triolein at 298.15 K. Results of 100 ns simulations at constant temperature and pressure to simulate mixing experiments show that in the first 10 ns all the binary mixtures remain largely unmixed. However, for the cosolvents that are fully miscible with triolein, the partial densities across the simulation boxes show that the systems are fully mixed in the final 10 ns. Some solvents were found to interact strongly with the polar part of triolein, while others interacted with the aliphatic part. The radial distribution functions and clustering of the solvents around triolein were also used as indicators for solvation. The presence of cosolvents also influenced the conformation of triolein molecules. In the presence of solvents that solubilize it, triolein preferred a propeller conformation but took up a trident conformation when there is less or no solubilization. The results show that tetrahydrofuran is the best solvent at solubilizing triolein, followed by cyclopentyl methyl ether, diethyl ether, and hexane. With 1,4-dioxane, the solubility improves with an increase in temperature. The miscibility of a solvent in triolein is aided by its ability to interact with both the polar and nonpolar parts of triolein.

The Pursuit of Shortwave Infrared-Emitting Nanoparticles with Bright Fluorescence through Molecular Design and Excited-State Engineering of Molecular Aggregates.

Shortwave infrared (SWIR) fluorescence detection gradually becomes a pivotal real-time imaging modality, allowing one to elucidate biological complexity in deep tissues with subcellular resolution. The key challenge for the further growth of this imaging modality is the design of new brighter biocompatible fluorescent probes. This review summarizes the recent progress in the development of organic-based nanomaterials with an emphasis on new strategies that extend the fluorescence wavelength from the near-infrared to the SWIR spectral range and amplify the fluorescence brightness. We first introduce the most representative molecular design strategies to obtain near-infrared-SWIR wavelength fluorescence emission from small organic molecules. We then discuss how the formation of nanoparticles based on small organic molecules contributes to the improvement of fluorescence brightness and the shift of fluorescence to SWIR, with a special emphasis on the excited-state engineering of molecular probes in an aggregate state and spatial packing of the molecules in nanoparticles. We build our discussion based on a historical perspective on the photophysics of molecular aggregates. We extend this discussion to nanoparticles made of conjugated polymers and discuss how fluorescence characteristics could be improved by molecular design and chain conformation of the polymer molecules in nanoparticles. We conclude the article with future directions necessary to expand this imaging modality to wider bioimaging applications including single-particle deep tissue imaging. Issues related to the characterization of SWIR fluorophores, including fluorescence quantum yield unification, are also mentioned.

Schistosomicidal evaluation of synthesized bromo and nitro chalcone derivatives

Chalcones are compounds associated to several biological activities. The modification of chemical structures is one of the most widely used tool in the pharmaceutical industry to obtain new drugs. In this study, we synthetized chalcones with nitro and bromo substituents in different positions in the aromatic rings. NMR spectroscopy was used for characterization. Simultaneously, a conformational study of the compounds was carried out employing theoretical calculations. Furthermore, the schistosomicidal in vitro effect of bromo and nitro chalcone substituents on adult Schistosoma mansoni was investigated. The results showed that most chalcones have a conformational preference for s-cis geometry, which is favored by the conjugative effect of electronic delocalization. However, chalcones with ortho substituents dissipate greater stabilization of s-trans conformations, possibly for favoring surfaces with weak interactions such as Van der Waals. In addition, a significant effect of chalcones on female and male S. mansoni was observed. All samples evaluated reduced the motor activity of worms, caused mortality in male and female worms, and resulted in morphological alterations in a concentration- dependent manner (25–200 μg/mL) in a period of 6–24 h of incubation. Additionally, chalcones influenced the separation of couple worms and suppressed egg production at sublethal concentrations. Our results demonstrated that chalcones present potential to be used as schistosomicidal drugs, contributing to the clarification of the relation between the molecule conformation and the associated biological effects.

Semi-flexible star-shaped molecules: conformational analysis of nano-segregated mesogens forming columnar liquid-crystal phases

Abstract The structural prerequisites are investigated, which make star-shaped molecules suitable precursors for the formation of columnar liquid-crystalline phases. Electronic structure calculations on smaller mesogens show that not all conformers exhibit the atomistic structure, the stability against distortion, and additional dipole moments, which favour columnar stacking. For the presently studied compounds with short terminating alkyl chains, the calculations indicate that the steric factor becomes dominant with increasing star size. Thus, the optimised geometric structures were employed to generate a simplified mathematical model of the structures, which accounts only for the steric interaction in the larger stars. With the help of these diagrams, the most common conformers of star-shaped molecules can be derived in a systematic fashion.

Promoting a desired conformational preference of an aromatic amide in various crystals by rational design of intramolecular hydrogen bonding

Although the conformational mobility of flexible ligands provides a way to generate structural diversity in the crystalline structure, strategies are needed to promote a conformational preference based on rational design. Herein, two methoxy groups were introduced onto N,N'-bis(4-pyridyl)isophthalamide (BPI) in order to gain a conformational preference by intramolecular hydrogen bonding. Therefore, we synthesized 4,6-dimethoxy-N,N'-bis(4-pyridyl)isophthalamide (DMBPI), and further prepared organic crystals and coordination polymers of DMBPI. Single crystal X-ray diffraction revealed that all DMBPI molecules in these crystals adopt anti,anti-conformations owing to the intramolecular-hydrogen-bond formation. In contrast, the diverse conformations of BPI molecules in the 27 BPI-containing crystals are categorized into three conformation types. The remarkable difference in conformational distribution may be attributed to that the energy gaps between the different conformations of DMBPI are significantly greater than those of BPI on the basis of density functional theory calculations. These results demonstrate that introduction of a suitable substituent to form intramolecular hydrogen bonds is an effective and rational strategy for achieving an expected conformation of molecules in crystals, which may facilitate the design and controllable assembly of functional materials.

Morphological Behavior of DPPC-DMPC Two-dimensional Mixed Monolayer on Water Surface by Dropping Method

We have investigated the morphology of dipalmitoyl phosphatidyl choline (DPPC)-dimyristoyl PC (DMPC) mixed monolayer formed on the water surface by the dropping method using surface tension measurement (STm), Brewster angle microscopy (BAM), and infrared external reflection spectroscopy (IERS). The limiting molecular area (A0) obtained by STm showed that the negative deviation at < mole fraction (xDMPC)= 0.4 whereas the positive deviation at > xDMPC =0.6 when DMPC was added to the DPPC monolayer. BAM images also showed that the condensed rigid monolayer at xDMPC < 0.4 changed to the expandable monolayer at xDMPC > 0.5. Moreover, IER spectra showed that the alkyl chains of both DPPC and DMPC molecules are in trans conformation in mixed monolayer at xDMPC =0.2 whereas gauche conformation existed at xDMPC = 0.8. Above findings have justified the transition of flexible gauche conformation alkyl chains of DMPC molecule into rigid trans conformation by the addition of DPPC molecule at xDMPC < 0.4 whereas alkyl chains retained flexible gauche conformation in both DPPC and DMPC molecules at xDMPC > 0.6.

Comparative Molecular Modelling of Capsular Polysaccharide Conformations in Streptococcus suis Serotypes 1, 2, 1/2 and 14 Identifies Common Epitopes for Antibody Binding.

Streptococcus suis is an encapsulated, commensal, potentially pathogenic bacterium that infects swine globally and causes sporadic life-threatening zoonotic septicemia and meningitis infections in humans. The capsular polysaccharide is a primary virulence factor for S. suis. As S. suis serotype 2 is the most prevalent serotype globally, the serotype 2 CPS is the primary target of current efforts to develop an effective glycoconjugate veterinary vaccine against S. suis. Possible cross-protection with related serotypes would broaden the coverage of a vaccine. The CPS in serotypes 2 and 1/2 differ at a single residue (Gal versus GalNAc), and both are similar to serotypes 1 and 14: all contain a terminal sialic acid on a side chain. However, despite this similarity, there is complex pattern of cross-protection for these serotypes, with varying estimations of the importance of sialic acid in a protective epitope. Further, a pentasaccharide without the terminal sialic acid has been identified as minimal epitope for serotype 2. Here we use molecular simulation to model the molecule conformations of the CPS in serotypes 2, 1/2, 1 and 14, as well as three vaccine candidate oligosaccharides. The common epitopes we identify assist in rationalizing the apparently contradictory immunological data and provide a basis for rational design of S. suis vaccines in the future.

Quantitative Structure Activity Relationship Analysis of Antiviral Activity of PF74 Type HIV-1 Capsid Protein Inhibitors by Simplex Representation of Molecular Structure

Human immunodeficiency virus type 1 (HIV-1) capsid protein (CA) plays essential roles in both early and late stages of HIV-1 replication and it is an important target for developing new therapeutic drugs. In the present study, quantitative structure–activity relationships (QSARs) models were developed for a series of 46 derivatives of PF74 CA inhibitors binding to the HIV1 capsid. The Partial least square (PLS) method was applied to obtain QSAR models based on simplex representation of molecular structure (SiRMS). Molecular docking studies were performed to find the optimal conformation of molecules within the binding site, and to compute 3D SiRMS descriptors. The study produced several statistically significant and acceptable QSAR models (R2 = 0.98, Q2 = 0.76–0.78, R2 predict = 0.84). A consensus model developed from the five excellent PLS QSAR models which was statistically validated for its predictive power using cross-validation, Y-randomization, and applicability domain evaluation procedures. The obtained results have satisfactory statistical parameters within acceptable range. The model interpreted by a reverse analysis identified the molecular fragments that promote and interfere with antiviral activity and the degree to which they influence activity. The influence of the physical–chemical properties of the molecules on antiviral activity was determined. It has been observed that antiviral activity is mainly governed by electrostatic characteristics of molecular structure and hydrophobic factors. The results obtained may further assist in the design of new CA inhibitor compounds and prediction of their activity.

Soft X-ray Spectroscopy Simulations with Multiconfigurational Wave Function Theory: Spectrum Completeness, Sub-eV Accuracy, and Quantitative Reproduction of Line Shapes.

Multireference methods are known for their ability to accurately treat states of very different nature in many molecular systems, facilitating high-quality simulations of a large variety of spectroscopic techniques. Here, we couple the multiconfigurational restricted active space self-consistent field RASSCF/RASPT2 method (of the CASSCF/CASPT2 methods family) to the displaced harmonic oscillator (DHO) model, to simulate soft X-ray spectroscopy. We applied such an RASSCF/RASPT2+DHO approach at the K-edges of various second-row elements for a set of small organic molecules that have been recently investigated at other levels of theory. X-ray absorption near-edge structure (XANES) and X-ray photoelectron spectroscopy (XPS) are simulated with a sub-eV accuracy and a correct description of the spectral line shapes. The method is extremely sensitive to the observed spectral shifts on a series of differently fluorinated ethylene systems, provides spectral fingerprints to distinguish between stable conformers of the glycine molecule, and accurately captures the vibrationally resolved carbon K-edge spectrum of formaldehyde. Differences with other theoretical methods are demonstrated, which show the advantages of employing a multireference/multiconfigurational approach. A protocol to systematically increase the number of core-excited states considered while maintaining a contained computational cost is presented. Insight is eventually provided for the effects caused by removing core–electrons from a given atom in terms of bond rearrangement and influence on the resulting spectral shapes within a unitary orbital-based framework for both XPS and XANES spectra.

Electrochemically deposited molybdenum disulfide surfaces enable polymer adsorption studies using quartz crystal microbalance with dissipation monitoring (QCM-D)

Polymer and small molecules are often used to modify the wettability of mineral surfaces which facilitates the separation of valuable minerals such as molybdenum disulfide (MoS2) from gangue material through the process of froth flotation. By design, traditional methods used in the field for evaluating the separation efficacy of these additives fail to give proper access to adsorption kinetics and molecule conformation, crucial aspects of flotation where contact times may not allow for full thermodynamic equilibrium. Thus, there is a need for alternative methods for evaluating additives that accurately capture these features during the adsorption of additives at the solid/liquid interface. Here, we present a novel method for preparing MoS2 films on quartz crystals used for Quartz Crystal Microbalance with Dissipation (QCM-D) measurements through an electrochemical deposition process. The resulting films exhibit well-controlled structure, composition, and thickness and therefore are ideal for quantifying polymer adsorption. After deposition, the sensors can be annealed without damaging the quartz crystal, resulting in a phase transition of the MoS2 from the as-deposited, amorphous phase to the 2H semiconducting phase. Furthermore, we demonstrate the application of these sensors to study the interactions of additives at the solid/liquid interface by investigating the adsorption of a model polymer, dextran, onto both the amorphous and crystalline MoS2 surfaces. We find that the adsorption rate of dextran onto the amorphous surface is approximately twice as fast as the adsorption onto the annealed surface. These studies demonstrate the ability to gain insight into the short-term kinetics of interaction between molecules and mineral surface, behavior that is key to designing additives with superior separation efficiency.

Graph Neural Networks as a Potential Tool in Improving Virtual Screening Programs.

Despite the increasing number of pharmaceutical companies, university laboratories and funding, less than one percent of initially researched drugs enter the commercial market. In this context, virtual screening (VS) has gained much attention due to several advantages, including timesaving, reduced reagent and consumable costs and the performance of selective analyses regarding the affinity between test molecules and pharmacological targets. Currently, VS is based mainly on algorithms that apply physical and chemistry principles and quantum mechanics to estimate molecule affinities and conformations, among others. Nevertheless, VS has not reached the expected results concerning the improvement of market-approved drugs, comprising less than twenty drugs that have reached this goal to date. In this context, graph neural networks (GNN), a recent deep-learning subtype, may comprise a powerful tool to improve VS results concerning natural products that may be used both simultaneously with standard algorithms or isolated. This review discusses the pros and cons of GNN applied to VS and the future perspectives of this learnable algorithm, which may revolutionize drug discovery if certain obstacles concerning spatial coordinates and adequate datasets, among others, can be overcome.

Mapping the broadband circular dichroism of copolymer films with supramolecular chirality in time and space

Measurements of the electronic circular dichroism (CD) are highly sensitive to the absolute configuration and conformation of chiral molecules and supramolecular assemblies and have therefore found widespread application in the chemical and biological sciences. Here, we demonstrate an approach to simultaneously follow changes in the CD and absorption response of photoexcited systems over the ultraviolet−visible spectral range with 100 fs time resolution. We apply the concept to chiral polyfluorene copolymer thin films and track their electronic relaxation in detail. The transient CD signal stems from the supramolecular response of the system and provides information regarding the recovery of the electronic ground state. This allows for a quantification of singlet−singlet annihilation and charge-pair formation processes. Spatial mapping of chiral domains on femtosecond time scales with a resolution of 50 μm and diffraction-limited steady-state imaging of the circular dichroism and the circularly polarised luminescence (CPL) of the films is demonstrated.

New Bicyclic Azalide Macrolides Obtained by Tandem Palladium Catalyzed Allylic Alkylation/Conjugated Addition Reaction

Unprecedented tandem allylic alkylation/intermolecular Michael addition was used in the preparation of novel bicyclic azalides. NMR spectroscopy was used not only to unambiguously determine and characterize the structures of these unexpected products of chemical reaction but also to investigate the effect the rigid bicyclic modification has on the conformation of the whole molecule. Thus, some of the macrolides prepared showed antibacterial activity in the range of well-known antibiotic drug azithromycin.

Exact Maximum Clique Algorithm for Different Graph Types Using Machine Learning

Finding a maximum clique is important in research areas such as computational chemistry, social network analysis, and bioinformatics. It is possible to compare the maximum clique size between protein graphs to determine their similarity and function. In this paper, improvements based on machine learning (ML) are added to a dynamic algorithm for finding the maximum clique in a protein graph, Maximum Clique Dynamic (MaxCliqueDyn; short: MCQD). This algorithm was published in 2007 and has been widely used in bioinformatics since then. It uses an empirically determined parameter, Tlimit, that determines the algorithm’s flow. We have extended the MCQD algorithm with an initial phase of a machine learning-based prediction of the Tlimit parameter that is best suited for each input graph. Such adaptability to graph types based on state-of-the-art machine learning is a novel approach that has not been used in most graph-theoretic algorithms. We show empirically that the resulting new algorithm MCQD-ML improves search speed on certain types of graphs, in particular molecular docking graphs used in drug design where they determine energetically favorable conformations of small molecules in a protein binding site. In such cases, the speed-up is twofold.

Changes in properties of nano protein particles (NPP) of fish muscle stored at 4 °C and its application in food quality assessment

Nano protein particles (NPP) in solutions of myofibrillar protein extracted from northern snakeheads (Channa argus) were studied. The results revealed that their particles size kept growing from 177 ± 2 nm at day 0–218 ± 5 nm at day 3 after slaughter while the corresponding ζ-potential enhanced from −19.0 ± 0.2 mv to −9.0 ± 1.2 mv. In addition, NPP became compact during this period, as inferred by their fractal dimension (df). These changes could be ascribed to the myofibrillar protein's structural alteration, including protein molecule conformation change. The simultaneous food quality assessments upon fish muscle illustrated that they all had very strong positive correlations to those two properties of NPP (r ≥ 0.87). This indicates that these two properties (particle size and ζ-potential) have potential to food quality assessment.