Molecules In Aqueous Solution Research Articles

Mechanisms of ssDNA aptamer binding to Cd2+ in aqueous solution: A molecular dynamics study

ssDNA aptamers have been increasingly used to detect heavy metal ions as recognition elements due to their high affinity and specificity. However, the specific recognition and binding mechanisms between aptamers and most heavy metals were still unclear, which limits the development of aptamer-based detection methods. In this work, the interaction mechanisms of CD-2-1 aptamers with Cd2+ in aqueous solutions were investigated using molecular dynamic simulations. The most stable complex was found where Cd2+ binding at aptamer's stem-loop junction and preferred at the phosphate backbone or bases. Noteworthily, two binding modes of Cd2+ combining aptamer in aqueous solution were discovered: direct and indirect. In the former mode, Cd2+ directly coordinated O atoms of bases. For the latter, Cd2+ connected to bases with coordinated water molecules as bridges. Electrostatic interaction was found to be the main driving force, and differences of residues role between two binding modes were elucidated. Buffer molecules in aqueous solutions can stabilize aptamer-Cd2+ complex by hydrogen bonds. This study revealed the specific interaction mechanisms of aptamer with Cd2+ at an atomic level, which provided theoretical references for aptamer-based Cd2+ detection methods establishment as well as an efficient technical route of screening potential aptamers for heavy metal ions.

PEG: The Magic Bullet for Biophysical Analysis of Highly Aggregating Small Molecules in Aqueous Solutions.

Biophysical research plays a crucial role in drug discovery, but many druglike molecules are poorly soluble and prone to aggregation, making their analysis challenging and susceptible to artifacts. To address this issue, we propose an approach that uses poly(ethylene glycol) (PEG) as an excipient in aqueous buffers to reduce the propensity of small molecules to aggregate. We show how PEG allows us to measure the thermodynamics of a complex formed by a heterobifunctional Small Molecule (hSM) that brings two proteins together. Our model accounts for all of the equilibrium states of the small molecule in solution, resulting in more precise parameters for describing how the proteins and the ligand interact. These precise parameters are important for designing better lead molecules.

Determination of the Number of Free Water Molecules in Aqueous Solutions on the Basis of Interrelated Consideration of the Polarization Processes in Water in the THz Frequency Range

Determination of the Number of Free Water Molecules in Aqueous Solutions on the Basis of Interrelated Consideration of the Polarization Processes in Water in the THz Frequency Range

Direct determination of intramolecular structure of D2O in the first hydration shell of Ni2+

Time-of-flight (TOF) neutron diffraction measurements have been carried out for aqueous 6 mol% NiCl2 solution in D2O in order to obtain experimental information on intramolecular structure of D2O molecules involved in the first hydration shell of Ni2+. The O-D bond length, rg OD = 0.982 ± 0.002 Å has been determined through the least squares fitting analysis of the observed difference interference term between the NiCl2 solution and pure D2O in the high-Q region (14 ≤ Q ≤ 40 Å−1). The present O-D bond length is significantly longer than that determined for pure liquid D2O (rg OD = 0.978 ± 0.001 Å), confirming strong hydrogen bonds between D2O molecules in the first- and the second hydration shell of Ni2+. These results are in good agreement with the νOD-rOD relationship obtained from infrared spectra for uncoupled O-D stretching frequency of HDO and O-D bond length of D2O molecule in aqueous solutions determined by neutron diffraction.

Molecular Dynamics Study on the Aggregation Behavior of Triton X Micelles with Different PEO Chain Lengths in Aqueous Solution.

The aggregation structure of Triton X (TX) amphiphilic molecules in aqueous solution plays an important role in determining the various properties and applications of surfactant solutions. In this paper, the properties of micelles formed by TX-5, TX-114, and TX-100 molecules with different poly(ethylene oxide) (PEO) chain lengths in TX series of nonionic surfactants were studied via molecular dynamics (MD) simulation. The structural characteristics of three micelles were analyzed at the molecular level, including the shape and size of micelles, the solvent accessible surface area, the radial distribution function, the micelle configuration, and the hydration numbers. With the increase of PEO chain length, the micelle size and solvent accessible surface area also increase. The distribution probability of the polar head oxygen atoms on the surface of the TX-100 micelle is higher than that in the TX-5 or TX-114 micelle. In particular, the tail quaternary carbon atoms in the hydrophobic region are mainly located at the micelle exterior. For TX-5, TX-114, and TX-100 micelles, the interactions between micelles and water molecules are also quite different. These structures and comparisons at the molecular level contribute to the further understanding of the aggregation and applications of TX series surfactants.

Acetylcholine Conformational Flexibility and Its Neutral Hydrolysis in Aqueous Solution

AbstractEnzymatic hydrolysis is the main target to deal with ACh depletion. However, a recent study indicates that the non‐enzymatic one may contribute to the depletion. This study highlights the necessity of considering possible conformers, discrete‐continuum models, and dispersive effects for investigating the neutral (non‐enzymatic) hydrolysis of flexible molecules in aqueous solution. We systematically built the possible conformers within the first‐principles framework. The results confirm the reactivity of high‐energy ACh conformer towards neutral hydrolysis. We proposed that conformational changes occur before the hydrolysis. The calculated activation and reaction energy shows that the discrete‐continuum solvation model gives the closest result to experimental observations. This study also shows that neglecting dispersive effects brings unreliable structures in the initial state, which leads to unreliable activation energy.

Chirality of Alanine Molecules in Water Solvent: A Theoretical Perspective

Sequential quantum mechanics/molecular mechanics (QM/MM) calculations combining the average solvent electrostatic configuration (ASEC) and the free energy gradient method are employed to locate minimum structures of α- and β-alanine in a water environment. Herein, we study the solvation effects in the nuclear magnetic resonance (NMR) spectroscopy, vibrational circular dichroism (VCD) spectroscopy, and electronic circular dichroism (ECD) spectroscopy of dl-α-alanine and β-alanine molecules. Our results point out that the ASEC-FEG (average solvent electrostatic configuration with the free energy gradient) method is a suitable approach for finding equilibrium structures of the alanine molecules in aqueous solution. Its accuracy is checked by comparing the optimized structures with those reached by the polarizable continuum model (PCM) and via experimental data. NMR parameters and vibrational and electronic UV-vis spectra are computed with a remarkable agreement with their corresponding experimental values.

Inequivalent Solvation Effects on the N 1s Levels of Self-Associated Melamine Molecules in Aqueous Solution.

This work shows how the N 1s photoemission (PE) spectrum of self-associated melamine molecules in aqueous solution has been successfully rationalized using an integrated computational approach encompassing classical metadynamics simulations and quantum calculations based on density functional theory (DFT). The first approach allowed us to describe interacting melamine molecules in explicit waters and to identify dimeric configurations based on π-π and/or H-bonding interactions. Then, N 1s binding energies (BEs) and PE spectra were computed at the DFT level for all structures both in the gas phase and in an implicit solvent. While pure π-stacked dimers show gas-phase PE spectra almost identical to that of the monomer, those of the H-bonded dimers are sensibly affected by NH···NH or NH···NC interactions. Interestingly, the solvation suppresses all of the non-equivalences due to the H-bonds yielding similar PE spectra for all dimers, matching very well our measurements.

Rational design of wettability-patterned microchips for high-performance attomolar surface-enhanced Raman detection

Recent progress in wettability-patterned microchips has facilitated the development of ultra-trace detection in multiple biomedical and food safety fields. The existence of a superhydrophilic trap can realize targeted deposition of the analyte. However, the wetting transition from the Cassie-Baxter state to the Wenzel state usually occurs during evaporation and leads to a larger deposition footprint, which has a strong impact on the detection sensitivity and uniformity. In this paper, we report an integrated design, fabrication, and evaporation strategy to avoid the transition for high-performance attomolar surface-enhanced Raman scattering (SERS) detection. An improved force balance model was proposed to design the microstructures of wettability-patterned microchips, which were fabricated by nanosecond laser direct writing and surface fluorination. The microchips were composed of superhydrophobic micro-grooves and superhydrophilic traps, by which the targeted deposition of Au nanoparticles and rhodamine 6G (R6G) onto a minimal area of ∼70 × 70 μm2 was realized after a two-step heated evaporation. Accordingly, the detection limit was down to the attomolar level (5 × 10−18 M) with SERS enhancement factors (EFs) exceeding 1010. More importantly, the Raman signals showed good uniformity (RSD of 11.5%) for the concentration of 2 × 10−17 M. A good linear relationship was obtained in the quantitative concentration range of 10−12 M to 5 × 10−18 M with a high correlation coefficient (R2) of 0.996. These wettability-patterned microchips exhibit high performance (that is, both good sensitivity and good uniformity) in the detection of ultra-trace molecules in aqueous solutions, avoiding the need for expensive equipment and considerable skill in operations. The proposed strategy could also be applied to other microfluidic devices for rapid and simple analyte pre-concentration.

New Implementation of an Equation-of-Motion Coupled-Cluster Damped-Response Framework with Illustrative Applications to Resonant Inelastic X-ray Scattering

We present an implementation of a damped response framework for calculating resonant inelastic X-ray scattering (RIXS) at the equation-of-motion coupled-cluster singles and doubles (CCSD) and second-order approximate coupled-cluster singles and doubles (CC2) levels of theory in the open-source program eT. This framework lays the foundation for future extension to higher excitation methods (notably, the coupled-cluster singles and doubles with perturbative triples, CC3) and to multilevel approaches. Our implementation adopts a fully relaxed ground state and different variants of the core-valence separation projection technique to address convergence issues. Illustrative results are compared with those obtained within the frozen-core core-valence separated approach, available in Q-Chem, as well as with experiment. The performance of the CC2 method is evaluated in comparison with that of CCSD. It is found that, while the CC2 method is noticeably inferior to CCSD for X-ray absorption spectra, the quality of the CC2 RIXS spectra is often comparable to that of the CCSD level of theory, when the same valence excited states are probed. Finally, we present preliminary RIXS results for a solvated molecule in aqueous solution.

Features of l-Tryptophan Solvation in Some Water–Organic Mixtures at T = 298.15 K

The effect of changes in the composition of some water–organic mixtures on the thermodynamic parameters of dissolution and solvation of l-tryptophan was studied by the method of calorimetry of dissolution at T = 298.15 K. To explain the experimental results, the enthalpic coefficients of pairwise interactions between l-tryptophan and organic cosolvent molecules and the energy contributions of the side chain to the energy of intermolecular interactions are calculated, and the influence of some properties of organic solvents on these interactions is estimated. All the data obtained were compared with those for l-phenylalanine to reveal the influence of the side chain structure on the energy of intermolecular interactions of aromatic amino acids with organic solvent molecules in aqueous solutions.

Aryl-Extended and Super Aryl-Extended Calix[4]pyrroles: Design, Synthesis, and Applications.

ConspectusProteins exhibit high-binding affinity and selectivity, as well as remarkable catalytic performance. Their binding pockets are hydrophobic but also contain polar and charged groups to contribute to the binding of polar organic molecules in aqueous solution. In the past decades, the synthesis of biomimetic receptors featuring sizable aromatic cavities equipped with converging polar groups has received considerable attention. "Temple" cages, naphthotubes, and aryl-extended calix[4]pyrroles are privileged examples of synthetic scaffolds displaying functionalized hydrophobic cavities capable of binding polar substrates. In particular, calix[4]pyrroles are macrocycles containing four pyrrole rings connected through their pyrrolic 2- and 5-positions by tetra-substituted sp3 carbon atoms (meso-substituents). In 1996, Sessler introduced the meso-octamethyl calix[4]pyrrole as an outstanding receptor for anion binding. Independently, Sessler and Floriani also showed that the introduction of aryl substituents in the meso-positions produced aryl-extended calix[4]pyrroles as a mixture of configurational isomers. In addition, aryl-extended calix[4]pyrroles bearing two and four meso-aryl substituents (walls) were reported. The cone conformation of "two-wall" αα-aryl-extended calix[4]pyrroles features an aromatic cleft with a polar binding site defined by four converging pyrrole NHs. On the other hand, "four-wall" αααα-calix[4]pyrrole isomers possess a deep polar aromatic cavity closed at one end by the converging pyrrole NHs. Because of their functionalized interior, aryl-extended calix[4]pyrroles are capable of binding anions, ion-pairs, and electron-rich neutral molecules in organic solvents. However, in water, they are restricted to the inclusion of neutral polar guests.Since the early 2000s, our research group has been involved in the design and synthesis of "two-wall" and "four-wall" aryl-extended calix[4]pyrroles and their derivatives, such as aryl-extended calix[4]pyrrole cavitands and super aryl-extended calix[4]pyrroles. In this Account, we mainly summarize our own results on the binding of charged and neutral polar guests with these macrocyclic receptors in organic solvents and in water. We also describe the applications of calix[4]pyrrole derivatives in the sensing of creatinine, the facilitated transmembrane transport of anions and amino acids, and the monofunctionalization of bis-isonitriles. Moreover, we explain the use of calix[4]pyrrole receptors as model systems for the quantification of anion-π interactions and the hydrophobic effect. Finally, we discuss the self-assembly of dimeric capsules and unimolecular metallo-cages based on calix[4]pyrrole scaffolds. We comment on their binding properties, as well as on those of bis-calix[4]pyrroles having a fully covalent structure.In molecular recognition, aryl-extended calix[4]pyrroles and their derivatives are considered valuable receptors owing to their ability to interact with a wide variety of electron-rich, neutral, and charged guests. Calix[4]pyrrole scaffolds have also been applied in the development of molecular sensors, ionophores, transmembrane carriers, supramolecular protecting groups and molecular containers modulating chemical reactivity, among others. We believe that the design of new calix[4]pyrrole receptors and the investigation of their binding properties may lead to promising applications in many research areas, such as supramolecular catalysis, chemical biology and materials science. We hope that this Account will serve to spread the knowledge of the supramolecular chemistry of calix[4]pyrroles among supramolecular and nonsupramolecular chemists alike.

An Acrylonitrile-Based Copolymer Gel as an NMR Alignment Medium for Extraction of Residual Dipolar Couplings of Small Molecules in Aqueous Solution.

An NMR weakly-aligning polymer gel has been prepared by copolymerization of acrylonitrile and 2-acrylamide-2-methyl-1-propanesulfonic acid in the presence of 1,4-butanediol diacrylate as a cross-linker. The polymer readily swells in water in a large range of temperatures, although the swelling ratio is decreased in saline solutions. The swollen gel can be mechanically compressed, in a reversible way, generating anisotropy, as easily shown in 2 H NMR experiments, and allowing measurement of 1 DCH residual dipolar couplings (RDCs) through F1-coupled HSQC experiments. The performance of this gel as a NMR alignment medium was evaluated in several water-soluble organic molecules and, while it provided RDCs of proper size for sucrose and even such as small molecule as 5-norbornen-2-ol, in the case of azidothymidine and cefuroxime sodium salt the strong interaction of these molecules with the gel prevented successful extraction of the RDCs.

Solubilisation and Enhanced Oral Absorption of Curcumin Using a Natural Non-Nutritive Sweetener Mogroside V.

Curcumin (CUR) is a functional ingredient from the spice turmeric. It has attracted considerable attention recently, owing to its diverse biological activities. However, curcumin has low water solubility, which limited its applications. Some sugar molecules were found to be able to solubilise poorly water-soluble compounds by forming micelles in aqueous solutions. To improve the water solubility and oral absorption of CUR, using a non-nutritive natural sweetener, namely, Mogroside V (Mog-V). A solid dispersion of CUR in Mog-V was prepared using a solvent evaporation method. The solid dispersion was characterised by using X-ray diffraction and differential scanning calorimetry. The solid dispersion can dissolve in water to form micelles with a diameter of ~160 nm, which were characterised by using dynamic light scattering. To find out the mechanism of solubilisation, the aggregation behaviour of Mog-V molecules in aqueous solution was investigated using nuclear magnetic resonance spectroscopy. Finally, oral absorption of CUR in the solid dispersion was evaluated using a rodent model. A solid dispersion was formed in a ratio of 1 CUR to 10 Mog-V by weight. Upon dissolution into water, CUR laden micelles formed via self-assembly of Mog-V molecules, which increased the solubility of CUR by nearly 6000 times compared with pure CUR crystals. In rats, the solid dispersion increased the oral absorption of CUR by 29 folds, compared with CUR crystals. In terms of solubilisation mechanism, it was found that Mog-V self-assembled into micelles with a core-shell structure and CUR molecules were incorporated into the hydrophobic core of the Mog-V micelles. Mog-V can form a solid dispersion with CUR. Upon dissolution in water, the Mog-V in the solid dispersion can self-assemble into micelles, which solubilise CUR and increase its oral absorption.

Theoretical study of Ponceau S oxidation using the electro-Fenton process under optimal operational conditions.

Electrochemical methods as one of the Advanced Oxidation Processes (AOPs) have been applied effectively to the degradation of recalcitrant organic molecules in aqueous solutions. In the present study, the performance of the electro-Fenton (EF) process on the oxidation of Ponceau S(PS) dye was studied. The experimental study performed at the optimal factors like the solution pH, the PS concentration and the ferrous ions dose provided 74.35% of PS degradation. The results, however, showed a decreased removal efficiency of PS when using sodium sulphate as the supporting electrolyte. From a theoretical point of view, the hydroxyl radical being an electron acceptor and the PS dye an electron donor, from a theoretical point of view, the hydroxyl radical being an electron acceptor and the PS dye an electron donor, furthermore, the nitrogen atom 2N being the most nucleophilic site of the PS dye with the most electrophilic site of the hydroxyl radical being the oxygen atom, the first stage of the reaction between PS and the hydroxyl radical was suggested.

Studying of the temperature influence on stability of fibrinogen macromolecules in aqueous solution: A literature mini-review

A review of the literature, multiple authors in order to systematize information on the effect of temperature in the range of 25-42 ° C on blood proteins, to conduct further studies of the effect of temperature on the stability of fibrinogen molecules in aqueous solution. Study of works on the determination of conformation and stability of protein molecules in the temperature range of living organisms.

Reaction-driven assembly: controlling changes in membrane topology by reaction cycles.

Chemical reaction cycles are prototypical examples how to drive systems out of equilibrium and introduce novel, life-like properties into soft-matter systems. We report simulations of amphiphilic molecules in aqueous solution. The molecule's head group is permanently hydrophilic, whereas the reaction cycle switches the molecule's tail from hydrophilic (precursor) to hydrophobic (amphiphile) and vice versa. The reaction cycle leads to an arrest in coalescence and results in uniform vesicle sizes that can be controlled by the reaction rate. Using a continuum description and particle-based simulation, we study the scaling of the vesicle size with the reaction rate. The chemically active vesicles are inflated by precursor, imparting tension onto the membrane and, for specific parameters, stabilize pores.

Calculation of the Proportion of Free Water Molecules in Aqueous Solutions Using the Parameters of Their Dielectric Permittivity in the Terahertz Range, Based on the Onsager Theory

The question of the structure of aqueous solutions is one of the most fundamental and complex, while it is relevant to all natural science disciplines. An important parameter of the dynamically equilibrium structure of an aqueous solution is the number of free water molecules. To date, there are no reliable and fully justified methods for determining this parameter. Recently, the terahertz time-domain spectroscopy (THz-TDS) method has been developing. It makes it possible to record the spectra of the complex permittivity in the THz region, where an orientation relaxation band of free water molecules is detected for aqueous solutions. The purpose of this work is to establish the relationship of the parameters of THz dielectric permittivity with the number of free water molecules. For this purpose, the process of polarization of water in the THz region was theoretically considered using the formalism of electrodynamics of continuous media. The Onsager theory is taken as a basis and its development is carried out for the case of high-frequency fields. As a result, an analytical ratio was obtained for calculating the proportion of free water molecules in solutions. A comparison with other well-known, more simplified and poorly substantiated approaches is presented. Calculations of the fraction of free molecules for a number of aqueous solutions have been carried out. It can be argued that the first theoretically justified approach to calculating the population of free water molecules in a solution, which does not contain internal contradictions, is presented.

Ab Initio Studies of NMNH(2-) Conformers in Water-Methanol Solutions: Comparative Analysis of the Biexponential Fluorescence Signals for NMNH(2-) and NADH.

Ab initio studies of the structure of reduced β-nicotinamide d-ribonucleotide (NMNH(2-)) conformations in water and methanol solutions have been carried out for clarifying the role of the phosphate groups in fluorescence parameters of the NMNH(2-) molecule and the reduced β-nicotinamide adenine dinucleotide (NADH) molecule. Relaxed potential energy surfaces as a function of the dihedral rotation angle of the amide group in the NMNH(2-) molecule were calculated in the ground electronic state and the first excited electronic state to better understand the effect of phosphate groups on the nonradiative decay rates in the nicotinamide chromophore groups. The differences in the weighting coefficients in the biexponential fluorescence signals for NMNH(2-) and NADH molecules in solution were explained. A strong hydrogen bonding between the amide hydrogen atom and the nearest oxygen O- atom from the phosphate group was detected by ab initio calculations for the folded NMNH(2-) conformations in the ground electronic state at trans configurations of the nicotinamide ring. This hydrogen bonding turned out to be much weaker for the first excited electronic state. These calculated data show that, after optical excitation of the NMNH(2-) molecule, a rapid change in the geometry of the molecule is possible. The strong interaction of the phosphate group with the amide group in NMNH(2-) molecules in aqueous solution leads to the predominance of the folded NMNH(2-) conformations and trans configurations of the nicotinamide ring. This explains the reason for the dominance of one fluorescence decay time of NMNH(2-) in the aqueous solution. Based on these data, an important conclusion can be drawn that the contribution of the exponent with the short decay time τ ≈ 0.28 ns to the fluorescence signal of NMNH(2-), NADH, and NADPH molecules is related to the trans configuration of the nicotinamide ring.

SOMAS: a platform for data-driven material discovery in redox flow battery development

Aqueous organic redox flow batteries offer an environmentally benign, tunable, and safe route to large-scale energy storage. The energy density is one of the key performance parameters of organic redox flow batteries, which critically depends on the solubility of the redox-active molecule in water. Prediction of aqueous solubility remains a challenge in chemistry. Recently, machine learning models have been developed for molecular properties prediction in chemistry and material science. The fidelity of a machine learning model critically depends on the diversity, accuracy, and abundancy of the training datasets. We build a comprehensive open access organic molecular database “Solubility of Organic Molecules in Aqueous Solution” (SOMAS) containing about 12,000 molecules that covers wider chemical and solubility regimes suitable for aqueous organic redox flow battery development efforts. In addition to experimental solubility, we also provide eight distinctive quantum descriptors including optimized geometry derived from high-throughput density functional theory calculations along with six molecular descriptors for each molecule. SOMAS builds a critical foundation for future efforts in artificial intelligence-based solubility prediction models.