Viscosity effects on the dynamics of diols and diol-based deep eutectic solvents.

Diols, characterized by the presence of two hydroxyl groups, form extended hydrogen-bonded networks. Increasing hydrocarbon chain length is known to elevate the viscosity of diols. Given the established influence of viscosity on solvent dynamics, it becomes imperative to comprehend the impact of viscosity on the fluctuation dynamics within diols and establish connections with hydrogen bond formation and breaking dynamics. In this study, we employ two-dimensional infrared spectroscopy to investigate the viscosity dependence of the structural evolution dynamics in three diols with varying chain lengths. Complementing our experimental approach, molecular dynamics simulations are conducted to extract hydrogen bond lifetimes. Our findings reveal a linear correlation between bulk viscosity, solvent fluctuation timescales, and hydrogen bond lifetimes. Notably, the selected diols exhibit the capability to form deep eutectic solvents upon mixing with choline chloride at specific molar ratios. In contrast to molecular solvents like diols, deep eutectic solvents are characterized by the formation of heterogeneous nanodomains, comprising various intercomponent hydrogen-bonded networks. Interestingly, our observations indicate that while the fluctuation dynamics decelerate with increasing bulk viscosity in diol-based deep eutectic solvents, the relationship between viscosity and dynamics is not linear, in contrast to the observed linearity in diols. This nuanced understanding contributes to the broader comprehension of the interplay between viscosity and dynamics in both molecular and deep eutectic solvents.

Perturbation of Fermi Resonance on Hydrogen-Bonded > C═O: 2D IR Studies of Small Ester Probes.

We utilized linear and 2D infrared spectroscopy to analyze the carbonyl stretching modes of small esters in different solvents. Particularly noteworthy were the distinct carbonyl spectral line shapes in aqueous solutions, prompting our investigation of the underlying factors responsible for these differences. Through our experimental and theoretical calculations, we identified the presence of the hydrogen-bond-induced Fermi resonance as the primary contributor to the varied line shapes of small esters in aqueous solutions. Furthermore, our findings revealed that the skeletal deformation mode plays a crucial role in the Fermi resonance for all small esters. Specifically, the first overtone band of the skeletal deformation mode intensifies when hydrogen bonds form with the carbonyl group of esters, whereas such coupling is rare in aprotic organic solvents. These spectral insights carry significant implications for the utilization of esters as infrared probes in both biological and chemical systems.

A Systematic Study on the Role of Hydrogen Bond Donors in Dictating the Dynamics of Choline-Based Deep Eutectic Solvents.

Deep eutectic solvents, promising green alternatives to conventional solvents, consist of a hydrogen bond donor and a hydrogen bond acceptor. The hydrogen bonding components in deep eutectic solvents form an extended hydrogen bonding network, which can be tuned to specific applications by changing the hydrogen bond donors. In this work, we have changed the hydrogen bond donor from a diol to a dicarboxylic acid by systematically replacing a hydroxyl group with an acid group one at a time to investigate the solvation structure and dynamics of the deep eutectic systems. Using a combination of ultrafast vibrational spectroscopy and molecular dynamics simulations, we compared the spectral diffusion and orientational relaxation dynamics of three deep eutectic systems using the vibrational responses of a dissolved anion. Our results indicate that although the solvation structures are marginally different across the systems, distinct differences are present in the solvent fluctuation and solute reorientation dynamics. This work provides a detailed molecular understanding of carboxylic-acid-based deep eutectic systems and how they differ from alcohol-based deep eutectic systems.

Does variation in composition affect dynamics when approaching the eutectic composition?

Deep eutectic solvent is a mixture of two or more components, mixed in a certain molar ratio, such that the mixture melts at a temperature lower than individual substances. In this work, we have used a combination of ultrafast vibrational spectroscopy and molecular dynamics simulations to investigate the microscopic structure and dynamics of a deep eutectic solvent (1:2 choline chloride: ethylene glycol) at and around the eutectic composition. In particular, we have compared the spectral diffusion and orientational relaxation dynamics of these systems with varying compositions. Our results show that although the time-averaged solvent structures around a dissolved solute are comparable across compositions, both the solvent fluctuations and solute reorientation dynamics show distinct differences. We show that these subtle changes in solute and solvent dynamics with changing compositions arise from the variations in the fluctuations of the different intercomponent hydrogen bonds.

Elucidation of pH-Induced Protein Structural Changes: A Combined 2D IR and Computational Approach.

The acid-base behavior of amino acids plays critical roles in several biochemical processes. Depending on the interactions with the protein environment, the pKa values of these amino acids shift from their respective solution values. As the side chains interact with the polypeptide backbone, a pH-induced change in the protonation state of aspartic and glutamic acids might significantly influence the structure and stability of a protein. In this work, we have combined two-dimensional infrared spectroscopy and molecular dynamics simulations to elucidate the pH-induced structural changes in an antimicrobial enzyme, lysozyme, over a wide range of pH. Simultaneous measurements of the carbonyl signals arising from the backbone and the acidic side chains provide detailed information about the pH dependence of the local and global structural features. An excellent agreement between the experimental and the computational results allowed us to obtain a residue-specific molecular understanding. Although lysozyme retains the helical structure for the entire pH range, one distinct loop region (residues 65-75) undergoes local structural deformation at low pH. Interestingly, combining our experiments and simulations, we have identified the aspartic acid residues in lysozyme, which are influenced the most/least by pH modulation.

Blue Fluorescence of Cyano-tryptophan Predicts Local Electrostatics and Hydrogen Bonding in Biomolecules.

Cyano-tryptophan is an unnatural fluorescent amino acid that emits in the visible region. Along with the structural similarity with tryptophan, the unique photophysical properties of this fluorophore make it an ideal probe for biophysical research. Herein, combining fluorescence spectroscopy, infrared spectroscopy, and molecular dynamics simulations, we show that the cyano-tryptophan's emission energy quantifies the underlying bond-specific noncovalent interactions in terms of the electric field. We further report the use of fluorophore's emission energy to predict its hydrogen bond characteristics. We demonstrate that combining experiments with molecular dynamics simulations can provide the hydrogen bonding status of the nitrile moiety. In addition, we report a method to differentiate between aqueous and nonaqueous hydrogen-bonding partners. Using a phenomenological approach, we demonstrate that the presence of the cyano-indole moiety is responsible for the distinct correlations between the fluorophore's emission and the electrostatic forces on the nitrile bond. As indole is a privileged scaffold for both native amino acids and nucleobases, cyano-indoles will have many multifaceted applications.

Does Viscosity Drive the Dynamics in an Alcohol-Based Deep Eutectic Solvent?

Deep eutectic solvents, consisting of heterogeneous nanodomains of hydrogen-bonded networks, have evolved into a range of viscous fluids that find applications in several fields. As viscosity is known to influence the dynamics of other neoteric solvents like ionic liquids, understanding the effect of viscosity on deep eutectic solvents is crucial to realize their full potential. Herein, we combine polarization-selective pump-probe spectroscopy, two-dimensional infrared spectroscopy, and molecular dynamics simulations to elucidate the impact of viscosity on the dynamics of an alcohol-based deep eutectic solvent, ethaline. We compare the solvent fluctuation and solute reorientation time scales in ethaline with those in ethylene glycol, an ethaline constituent. Interestingly, we find that the solute's reorientation apparently scales the bulk viscosity of the solvent, but the same is not valid for the overall solvation dynamics. Using the variations in the estimated intercomponent hydrogen bond lifetimes, we show that a dissolved solute does not sense the bulk viscosity of the deep eutectic solvent; instead, it senses domain-specific local viscosity determined by the making and breaking of the hydrogen bond network. Our results indicate that understanding the domain-specific local environment experienced by the dissolved solute is of utmost importance in deep eutectic solvents.

Water-Controlled Keto-Enol Tautomerization of a Prebiotic Nucleobase.

Barbituric acid is believed to be a proto-RNA nucleobase that was used for biological information transfer on prebiotic earth before DNA and RNA in their present forms evolved. Nucleobases have various tautomeric forms and the relative stability of these forms is critical to their biological function. It has been shown that barbituric acid has a tri-keto form in the gas phase and an enol form in the solid state. However, its dominant tautomeric form in aqueous medium that is most relevant for biology has been investigated only to a limited extent and the findings are inconclusive. We have used multiple approaches, namely, molecular dynamics, quantum chemistry, NMR, and IR spectroscopy to determine the most stable tautomer of barbituric acid in solution. We find a delicate balance in the stability of the two tautomers, tri-keto and enol, which is tipped toward the enol as the extent of solvation by water increases.

On-Off Infrared Absorption of the S═O Vibrational Probe of Dimethyl Sulfoxide.

Dimethyl sulfoxide (DMSO), a polar solvent molecule, is used in a wide range of therapeutic and pharmacological applications. Different intermolecular interactions, such as dimerization and hydrogen bonding with water, are crucial to understanding the role of DMSO in applications. Herein, we study DMSO in various solvation environments to decipher the environment-dependent dimerization and hydrogen-bonding propensity. We use a combination of infrared spectroscopy, quantum mechanical calculations, and molecular dynamics simulations to reach our conclusions. Although DMSO can exist in a dynamic equilibrium between monomers and dimers, our results show that the relative intensity of the S═O stretch and the CH3 rocking modes is a spectroscopic indicator of the extent of DMSO dimerization in solution. The dimerization (self-association) is seen to be maximum in neat DMSO. When dissolved in different solvents, the dimerization propensity decreases with increasing solvent polarity. In the presence of a protic solvent, such as water, DMSO forms a hydrogen bond with the solvent molecules, thereby reducing the extent of dimerization. Further, we estimate the hydrogen-bond occupancy of DMSO. Our results show that DMSO predominantly exists as doubly hydrogen-bonded in water.

Predicting the Redox Potentials of Phenazine Derivatives Using DFT-Assisted Machine Learning.

This study investigates four machine-learning (ML) models to predict the redox potentials of phenazine derivatives in dimethoxyethane using density functional theory (DFT). A small data set of 151 phenazine derivatives having only one type of functional group per molecule (20 unique groups) was used for the training. Prediction accuracy was improved by a combined strategy of feature selection and hyperparameter optimization, using the external validation set. Models were evaluated on the external test set containing new functional groups and diverse molecular structures. High prediction accuracies of R 2 > 0.74 were obtained on the external test set. Despite being trained on the molecules with a single type of functional group, models were able to predict the redox potentials of derivatives containing multiple and different types of functional groups with good accuracies (R 2 > 0.7). This type of performance for predicting redox potential from such a small and simple data set of phenazine derivatives has never been reported before. Redox flow batteries (RFBs) are emerging as promising candidates for energy storage systems. However, new green and efficient materials are required for their widespread usage. We believe that the hybrid DFT-ML approach demonstrated in this report would help in accelerating the virtual screening of phenazine derivatives, thus saving computational and experimental costs. Using this approach, we have identified promising phenazine derivatives for green energy storage systems such as RFBs.

Ligand Dynamics Time Scales Identify the Surface-Ligand Interactions in Thiocyanate-Capped Cadmium Sulfide Nanocrystals.

The nanocrystal surface, which acts as an interface between the semiconductor lattice and the capping ligands, plays a significant role in the attractive photophysical properties of semiconductor nanocrystals for use in a wide range of applications. Replacing the long-chain organic ligands with short inorganic variants improves the conductivity and carrier mobility of nanocrystal-based devices. However, our current understanding of the interactions between the inorganic ligands and the nanocrystals is obscure due to the lack of experiments to directly probe the inorganic ligands. Herein, using two-dimensional infrared spectroscopy, we show that the variations in the inorganic ligand dynamics within the heterogeneous nanocrystal ensemble can identify the diversities in the inorganic ligand-nanocrystal interactions. The ligand dynamics time scale in SCN- capped CdS nanocrystals identifies three distinct ligand populations and provides molecular insight into the nanocrystal surface. Our results demonstrate that the SCN- ligands engage in a dynamic equilibrium and stabilize the nanocrystals by neutralizing the surface charges through both direct binding and electrostatic interaction.

Association-Dissociation Dynamics of Ionic Electrolytes in Low Dielectric Medium.

Ionic electrolytes are known to form various complexes which exist in dynamic equilibrium in a low dielectric medium. However, structural characterization of these complexes has always posed a great challenge to the scientific community. An additional challenge is the estimation of the dynamic association-dissociation time scales (lifetime of the complexes), which are key to the fundamental understanding of ion transport. In this work, we have used a combination of infrared absorption spectroscopy, two-dimensional infrared spectroscopy, molecular dynamics simulations, and density functional theory calculations to characterize the various ion complexes formed by the thiocyanate-based ionic electrolytes as a function of different cations in a low dielectric medium. Our results demonstrate that thiocyanate is an excellent vibrational reporter of the heterogeneous ion complexes undergoing association-dissociation dynamics. We find that the ionic electrolytes exist as contact ion pairs, dimers, and clusters in a low dielectric medium. The relative ratios of the various ion complexes are sensitive to the cations. In addition to the interactions between the thiocyanate anion and the countercation, the solute-solvent interactions drive the dynamic equilibrium. We have estimated the association-dissociation dynamics time scales from two-dimensional infrared spectroscopy. The exchange time scale involving the cluster is faster than that between a dimer and an ion pair. Moreover, we find that the dynamic equilibrium between the cluster and another ion complex is correlated to the solvent fluctuations.

Transition of a Deep Eutectic Solution to Aqueous Solution: A Dynamical Perspective of the Dissolved Solute.

Disruption of the deep eutectic solvent (DES) nanostructure around the dissolved solute upon addition of water is investigated by polarization-selective two-dimensional infrared spectroscopy and molecular dynamics simulations. The heterogeneous DES nanostructure around the solute is partially retained up to 41 wt % of added water, although water molecules are gradually incorporated in the solute's solvation shell even at lower hydration levels. Beyond 41 wt %, the solute is observed to be preferentially solvated by water. This composition denotes the upper hydration limit of the deep eutectic solvent above which the solute senses an aqueous solvation environment. Interestingly, our results indicate that the transition from a deep eutectic solvation environment to an aqueous one around the dissolved solute can happen at a hydration level lower than that reported for the "water in DES" to "DES in water" transition.

Stabilization of Azapeptides by Namide···H-Namide Hydrogen Bonds.

An unusual Namide···H-Namide hydrogen bond (HB) was previously proposed to stabilize the azapeptide ß-turns. Herein we provide experimental evidence for the Namide···H-Namide HB and show that this HB endows a stabilization of 1-3 kcal·mol-1 and enforces the trans-cis-trans (t-c-t) and cis-cis-trans (c-c-t) amide bond conformations in azapeptides and N-methyl-azapeptides, respectively. Our results indicate that these Namide···H-Namide HBs can have stabilizing contributions even in short azapeptides that cannot fold to form ß-turns.

Evidence of an nN(amide) → π*Ar Interaction in N-Alkyl-N,N'-diacylhydrazines.

1,2-Dibenzoyl-1-tert-butylhydrazine (RH-5849) and related N-alkyl-N,N'-diacylhydrazines are environmentally benign insect growth regulators. Herein, we show that an unusual nN(amide) → π*Ar interaction mediated by a hydrazide amide nitrogen atom plays a crucial role in stabilizing their biologically active trans-cis (t-c) rotameric conformations. We provide NMR and IR spectroscopic evidence for the presence of these interactions, which is also supported by X-ray crystallographic and computational studies.

The Curious Case of Aqueous Warfarin: Structural Isomers or Distinct Excited States?

Warfarin is a potent anti-coagulant drug and is on the World Health Organization's List of Essential Medicines. Additionally, it displays fluorescence enhancement upon binding to human serum albumin, making warfarin a prototype fluorescent probe in biology. Despite its biological significance, the current structural assignment of warfarin in aqueous solution is based on indirect evidence in organic solvents. Warfarin is known to exist in different isomeric forms-open-chain, hemiketal, and anionic forms-based on the solvent and pH. Moreover, warfarin displays a dual absorption feature in several solvents, which has been employed to study the ring-chain isomerism between its open-chain and hemiketal isomers. In this study, our pH-dependent experiments on warfarin and structurally constrained warfarin derivatives in aqueous solution demonstrate that the structural assignment of warfarin solely on the basis of its absorption spectrum is erroneous. Using a combination of steady-state and time-resolved spectroscopic experiments, along with quantum chemical calculations, we assign the observed dual absorption to two distinct π → π* transitions in the 4-hydroxycoumarin moiety of warfarin. Furthermore, we unambiguously identify the isomeric form of warfarin that binds to human serum albumin in aqueous buffer.

Electrostatic Manifestation of Micro-Heterogeneous Solvation Structures in Deep-Eutectic Solvents: A Spectroscopic Approach.

Deep eutectic solvents have emerged as inexpensive green alternatives to conventional solvents for diverse applications in chemistry and biology. Despite their importance as useful media in various applications, little is known about the microscopic solvation structures of deep eutectic solvents around solutes. Herein, we show that the electrostatic field, which can be estimated both from infrared experiments and theory, can act as a unified concept to report on the microscopic heterogeneous solvation of deep eutectic solvents. Using a fluorophore containing the carbonyl moiety as the solute and the electrostatic field as a descriptor of the solvation structure of the deep eutectic solvents, we report the residue-specific distribution, orientation, and hydrogen bonding in deep eutectic solvents constituting of choline chloride and alcohols of varying chain-lengths. We observe that an increase in alcohol chain-length not only affects the alcohol's propensity to form hydrogen bond to the solute but also alters the spatial arrangement of choline cations around the solute, thereby leading to a microheterogeneity in the solvation structure. Moreover, to extend our electrostatic field based strategy to other deep eutectic solvents, we report an emission spectroscopy based method. We show that this method can be applied, in general, to all deep eutectic solvents, irrespective of their constituents. Overall, this work integrates experiments with molecular dynamics simulations to provide insights into the heterogeneous DES solvation.

Hydrocarbon Chain-Length Dependence of Solvation Dynamics in Alcohol-Based Deep Eutectic Solvents: A Two-Dimensional Infrared Spectroscopic Investigation.

Deep eutectic solvents (DESs) have gained popularity in recent years as an environmentally benign, inexpensive alternative to organic solvents for diverse applications in chemistry and biology. Among them, alcohol-based DESs serve as useful media in various applications due to their significantly low viscosity as compared to other DESs. Despite their importance as media, little is known how their solvation dynamics change as a function of the hydrocarbon chain length of the alcohol constituent. In order to obtain insights into the chain-length dependence of the solvation dynamics, we have performed two-dimensional infrared spectroscopy on three alcohol-based DESs by systematically varying the hydrocarbon chain length. The results reveal that the solvent dynamics slows down monotonically with an increase in the chain length. This increase in the dynamic timescales also shows a strong correlation with the concomitant increase in the viscosity of DESs. In addition, we have performed molecular dynamics simulations to compare with the experimental results, thereby testing the capacity of simulations to determine the amplitudes and timescales of the structural fluctuations on fast timescales under thermal equilibrium conditions.