Solvation Dynamics Research Articles

Understanding the solvation dynamics of metformin in water using theoretical tools

Metformin, brand nameGlucophage, is a medication used to regulate blood sugar levels in patients who have Type 2 diabetes. This drug has been in use for decades, and the main aim of this manuscript is to find how the drug interacts with a solvent system (water) using theoretical tools. We used PBE0-D3/def2-TZVP method for optimizations and other calculations and LED and AIMD PBE0-D3/def2-TZVP and DLPNO-CCSD(T) levels. There are five different possible locations of binding between metformin and water. Qualitative analysis of the non-covalent interactions showed hydrogen bonding interaction between them, which is confirmed by NBO and AIM studies. Local energy decomposition studies dissected the NCI quantitatively into different components. In the AIMD assay, the velocity of all atom's boundaries of metformin with solvent molecules simulations were calculated depending on time. The implicit solvation assay also shows the same result as LED and AIMD.

Ionic Conduction Mechanism and Design of Metal-Organic Framework Based Quasi-Solid-State Electrolytes.

We report the theoretical and experimental investigation of two polyoxometalate-based metal–organic frameworks (MOFs), [(MnMo6)2(TFPM)]imine and [(AlMo6)2(TFPM)]imine, as quasi-solid-state electrolytes. Classical molecular dynamics coupled with quantum chemistry and grand canonical Monte Carlo are utilized to model the corresponding diffusion and ionic conduction in the two materials. Using different approximate levels of ion diffusion behavior, the primary ionic conduction mechanism was identified as solvent-assisted hopping (>77%). Detailed static and dynamic solvation structures were obtained to interpret Li+ motion with high spatial and temporal resolution. A rationally designed noninterpenetrating MOF-688(one-fold) material is proposed to achieve 6–8 times better performance (1.6–1.7 mS cm–1) than the current state-of-the-art (0.19–0.35 mS cm–1).

OH Stretching and Libration Bands of Solitary Water in Ionic Liquids and Dipolar Solvents Share a Single Dependence on Solvent Polarity.

Ionic liquids are an emerging class of materials which are finding application in a variety of technologically important areas. Because of their hydrophilic character, at least a small concentration of water is often present when ionic liquids are used in practical applications. This study employs infrared spectroscopy in the OH stretching and libration regions together with DFT calculations to better characterize the state of dilute water in ionic liquids. Water mole fractions (xw ∼ 0.1) are chosen such that nearly all water occurs in monomeric form and spectra probe the solvation structure and dynamics of solitary water molecules. New data are reported for a series of 1-ethyl-3-methylimidazolium liquids [Im21][X] with X- = (C2F5)3F3P-, (CF3SO2)2N-, BF4-, B(CN)4-, CF3SO3-, C2H5SO4-, NO3-, SCN-, and CH3CO2-, as well as for the two 1-hexyl-3-methylimidazolium liquids [Im61][Cl] and [Im61][I]. For comparison, spectra are also recorded in a variety of dipolar solvents, and much of the available literature data are summarized, providing a comprehensive perspective on monomeric water in homogeneous solution. Most prior studies of dilute water in ionic liquids interpreted OH stretching spectra only in terms of water being specifically bonded to two anions in A-···H-O-H···A- type solvates. The more detailed analysis presented here indicates the additional presence of asymmetrically solvated water, which in some cases includes both singly solvated (A-···H-O-H) and more subtle forms of asymmetric solvation. The same pattern of solvation also pertains to dipolar solvents capable of accepting hydrogen bonds from water. No clear distinction is found between OH spectra in high-polarity conventional solvents and ionic liquids. In all solvents, OH frequencies are strongly correlated to measures of solvent basicity or hydrogen bond accepting ability. Far-infrared spectra of the water libration band also show common trends in ionic and dipolar solvents. Despite the different character of the libration and OH modes, the frequencies of these vibrations show virtually the same solvent dependence (apart from sign) except in weakly polar or nonpolar solvents.

In Situ Observation of the Structure of Crystallizing Magnesium Sulfate Heptahydrate Solutions with Terahertz Transmission Spectroscopy.

Terahertz time-domain spectroscopy in a transmission geometry combined with visual analysis was used to investigate the crystallization process of MgSO4 solution. Careful spectral analysis of both a feature at 1.6 THz and the overall magnitude of absorption allowed the extraction of information about the liquid phase before and during crystallization, aiding the investigation of solvation dynamics and the behavior of molecular species at phase boundaries. The method was reproducibly applied to a number of measurements on a series of solutions of three chosen concentrations at different temperatures. When increasing temperature at the end of the measurement, the dissolution of crystals was observed as well. The temperature-dependent absorption data of the semicrystalline systems were converted to the solvent concentrations using a recently developed method. Solutions of a series of concentrations were also investigated in the temperature range of 4–25 °C. The results were compared to the theoretical calculated values, and the consistent differences proved the existence of a hydration shell around the salt ions whose behavior is different from bulk water. Future work will focus on triggering nucleation at specific positions in order to study the very beginning of the crystallization process. MgSO4 heptahydrate is used as a model system in this study, while the concept and the setup can be applied to other systems.

Direct Observation of the Dynamics of Ylide Solvation by Hydrogen-bond Donors Using Time-Resolved Infrared Spectroscopy.

The photoexcitation of α-diazocarbonyl compounds produces singlet carbene intermediates that react with nucleophilic solvent molecules to form ylides. The zwitterionic nature of these newly formed ylides induces rapid changes in their interactions with the surrounding solvent. Here, ultrafast time-resolved infrared absorption spectroscopy is used to study the ylide-forming reactions of singlet carbene intermediates from the 270 nm photoexcitation of ethyl diazoacetate in various solvents and the changes in the subsequent ylide–solvent interactions. The results provide direct spectroscopic observation of the competition between ylide formation and C–H insertion in reactions of the singlet carbene with nucleophilic solvent molecules. We further report the specific solvation dynamics of the tetrahydrofuran (THF)-derived ylide (with a characteristic IR absorption band at 1636 cm–1) by various hydrogen-bond donors and the coordination by lithium cations. Hydrogen-bonded ylide bands shift to a lower wavenumber by −19 cm–1 for interactions with ethanol, −14 cm–1 for chloroform, −10 cm–1 for dichloromethane, −9 cm–1 for acetonitrile or cyclohexane, and −16 cm–1 for Li+ coordination, allowing the time evolution of the ylide–solvent interactions to be tracked. The hydrogen-bonded ylide bands grow with rate coefficients that are close to the diffusional limit. We further characterize the specific interactions of ethanol with the THF-derived ylide using quantum chemical (MP2) calculations and DFT-based atom-centered density matrix propagation trajectories, which show preferential coordination to the α-carbonyl group. This coordination alters the hybridization character of the ylidic carbon atom, with the greatest change toward sp2 character found for lithium-ion coordination.

Lipid Clustering in Mycobacterial Cell Envelope Layers Governs Spatially Resolved Solvation Dynamics.

The mycobacterial cell envelope acts as a multilayered barrier to drugs. However, the role of lipid composition in the properties of different mycobacterial membranes, otherwise dictating their interactions with drugs, is poorly understood. In this study, we found that hydration states, solvation relaxation kinetics, rotational lipid mobility, and lateral lipid diffusion differed between inner and outer mycobacterial membranes. Molecular modeling showed that lipid clustering patterns governed membrane dynamics in the different layers of the cell envelope. By regulating membrane properties, lipid composition and structure modulated water abundance and interactions with lipid head groups. These findings can help deepen our understanding of the physical chemistry underlying membrane structure and function, as well as the interaction of mycobacterial membranes with drugs and host membranes.

Field-Induced Electron Generation in Water: Solvation Dynamics and Many-Body Interactions

The solvated electron represents an elementary quantum system in a liquid environment. Electrons solvated in water have raised strong interest because of their prototypical properties, their role in radiation chemistry, and their relevance for charge separation and transport. Nonequilibrium dynamics of photogenerated electrons in water occur on ultrafast time scales and include charge transfer, localization, and energy dissipation processes. We present new insight into the role of fluctuating electric fields of the liquid for generating electrons in the presence of an external terahertz field and address polaronic many-body properties of solvated electrons. This Perspective combines a review of recent results from experiment and theory with a discussion of basic electric interactions of electrons in water.

Dependence of Quinone Electrochemistry on Solvent Polarity and pH

We studied the polarographic reduction of quinones in aqueous/organic mixtures with dielectric constants (ε) from 78.4 down to 47. Added organic co-solvents were either protic or aprotic. The increase in polarographic half-wave potential, E 1/2, with declining ε was successfully fit to the Born equation down to ε ≈ 55. Cu2+ and ubiquinone0 were reduced in a single two-electron step that was more ε-sensitive when the added organic co-solvent was aprotic. Naphtho- and anthraquinone were reduced in two successive one-electron steps that were influenced identically by protic or aprotic organic co-solvents. The product of the first reduction wave was neutral semiquinone (·QH), which surprisingly, had to be protonated to ·QH2 + before reduction in the second wave. Except for r H+, radii derived from fitting our E 1/2 vs ε results to the Born equation were too small; in other words, non-electrostatic effects destabilized the oxidized species, greatly enhancing the Born electrostatic increase in E 1/2 with declining ε. Additionally, for ε < 55, we observed deviation from the Born equation, which may be due to changes in solvent structure and dynamics, and solvent-solute interactions. Finally, we studied quinones incorporated into phosphatidyl choline sonicated bilayer vesicles: Ubiquinone0 had two distinct irreversible two-electron reduction waves, one due to a population bound at the membrane surface, and another (whose E 1/2 was negatively shifted by 150 mV) due to a population localized in the membrane interior. Ubiquinone10 had a single irreversible two-electron reduction wave that was 250 mV more negative than the UQ0 membrane-interior population.

Enhanced sensitivity of dilute aqueous adrenaline solution with an asymmetric hexagonal ring structure in the terahertz frequencies

Quantitative detection of neurotransmitters in aqueous environment is crucial for the early diagnosis of many neurological disorders. Terahertz waves, as a non-contact and non-labeling tool, have demonstrated large potentials in quantitative biosensing. Although the detection of trace-amount analyte has been achieved with terahertz metamaterials in the recent decades, most studies have been focused on dried samples. Here, a hexagonal asymmetric metamaterial sensor was designed and fabricated for aqueous solution sensing with terahertz waves in the reflection geometry. An absorption enhancement of 43 was determined from the simulation. Dilute adrenaline solutions ranging from 30 µM to 0.6 mM were measured on our sensor using a commercial terahertz time-domain spectroscopy system, and the effective absorption was found to be linearly correlated with the concentration (R2 = 0.81). Furthermore, we found that as the concentration becomes higher (>0.6 mM), a non-linear relationship starts to take place, which confirmed the previous theory on the extended solvation shell that can be probed on the picosecond scale. Our sensor, without the need of high-power and stable terahertz sources, has enabled the detection of subtle absorption changes induced by the solvation dynamics.

Hollow-core optical fibre sensors for operando Raman spectroscopy investigation of Li-ion battery liquid electrolytes

Improved analytical tools are urgently required to identify degradation and failure mechanisms in Li-ion batteries. However, understanding and ultimately avoiding these detrimental mechanisms requires continuous tracking of complex electrochemical processes in different battery components. Here, we report an operando spectroscopy method that enables monitoring the chemistry of a carbonate-based liquid electrolyte during electrochemical cycling in Li-ion batteries with a graphite anode and a LiNi0.8Mn0.1Co0.1O2 cathode. By embedding a hollow-core optical fibre probe inside a lab-scale pouch cell, we demonstrate the effective evolution of the liquid electrolyte species by background-free Raman spectroscopy. The analysis of the spectroscopy measurements reveals changes in the ratio of carbonate solvents and electrolyte additives as a function of the cell voltage and show the potential to track the lithium-ion solvation dynamics. The proposed operando methodology contributes to understanding better the current Li-ion battery limitations and paves the way for studies of the degradation mechanisms in different electrochemical energy storage systems.

Structure and dynamics of hydrophobic deep eutectic solvents composed from terpene-fatty acids investigated by molecular dynamics simulation

Hydrophobic deep eutectic solvents (HDES) composed of Terpenes and Fatty acids have recently been the subject of great interest for removing pollutants from an aqueous environment. Despite the specific application of Hydrophobic DES and the important role of molecular dynamics simulation in predicting the properties of these compounds, not many studies have been done on their intermolecular interaction. In this work, we performed molecular dynamics simulations for the eutectic mixture based on monoterpene (Menthol, Thymol) and Fatty acids such as Caprylic Acid, Decanoic Acid, Lauric Acid, and Myristic acid. Binary mixtures of Terpene and Fatty acids were prepared at molar ratios 1:1, and their properties were investigated at 323 K. We have carried out 50 ns in the ensemble NPT to understand thermo-physical properties that are largely dependent on the interaction between molecules. Here, the structural properties of the binary mixtures were evaluated, and the possible explanations for their thermo-physical properties have been presented. The interaction between Terpenes and Fatty acids was studied by the structural properties such as the atom-atom radial distribution functions (RDF) and the Hydrogen bonding network between species and Spatial distribution functions (SDF). The structural properties studies revealed that the interaction between Terpenes and Fatty acids decreased the reduction of the accumulation of Terpene molecules around each other in the binary mixtures. Evidence has been acquired that the interaction between the menthol molecules was mostly affected by the Fatty acids molecules. Also, the transport properties of the binary mixtures were explored using the mean-square displacement (MSD) for the centers of mass of molecules, self-diffusion of species, and vector reorientation dynamics (VRD) of bonds. The simulation results indicated that intermolecular interactions play an important role in the dynamic properties of species, and maintains the low melting point of the mixture.

A Trefoil Knot Polymer Chain Translocates through a Funnel-like Channel: A Multi-Particle Collision Dynamics Study.

With combining multi-particle collision dynamics (MPCD) for the solvent and molecular dynamics (MD) for the polymer chains, we have studied the conformation and untying behaviors of a trefoil knot polymer chain translocated through a confined funnel-like channel. For the trefoil knot chain, we found that the untying knot behavior mostly happens during the translocation process, and the translocation behavior of linear chains is also simulated as a comparison. Some characteristics of the trefoil knot chain during translocation process, such as average gyration radius <Rg> and the average end-to-end distances <S> are discussed, and we statistic the scale relations of the translocation time versus the chain length, and that of the chain rigidity. This study may help to understand translocation behaviors of the knotted linear polymer chain in the capillary flow field.

Hydrogen bonds between valsartan and solvents (water and methanol): Evidences for solvation dynamics using local energy decomposition and abinitio molecular dynamics analysis

The change in Gibbs energy when an ion or molecule moves from a vacuum to a solvent is known as solvation energy and solvation is the process of attracting and associating molecules of a solvent with molecules or ions of a solute. Valsartan belongs to the class of drugs known as angiotensin II inhibitors. It is primarily used to treat excessive blood pressure, congestive heart failure and improve the odds of living longer after a heart attack. The main aim of this paper is to study how solvent molecules like water and methanol interact with valsartan. The systems are optimized using the level DFT/B3LYP cc-pVDZ and this geometry was used for Natural bond orbital (NBO), bin-covalent interactions (NCI), and wavefunction assay. PBE0-D3/def2-TZVP is used to perform abinitio molecular dynamics (AIMD) simulations and DLPNO-CCSD(T) for Local Energy Decomposition (LED). Valsartan can produce five fragments: biphenylmethane-, butyl, isopropyl-, N-acyl-Nmethylglycine- and tetrazole, and bond energy (change in enthalpy) is 2451.11 kcal/mol. NBO shown orbital energies of valsartan in a vacuum and its complexes are in order of oxygen electron pairs is valsartan-water > valsartan-methanol > valsartan; similarly, nitrogen electron pairs valsartan-methanol > valsartan > valsartan-water and carbon electron pairs valsartan-water = valsartan-methanol > valsartan. NCI explains the noncovalent interactions of valsartan in vacuum and valsartan with water and methanol (complex) molecules; inter and intra interactions of them. Binding energies of interactions and total binding energies indicated that valsartan-water is of lower energy with more stability than valsartan-methanol is higher energy with less stable. AIMD of valsartan-water is greater simulations and valsartan-methanol is poor simulations between them.

Energy transfer and thermoelectricity in molecular junctions in non-equilibrated solvents

We consider a molecular junction immersed in a solvent where the electron transfer is dominated by Marcus-type steps. However, the successive nature of the charge transfer through the junction does not imply that the solvent reaches thermal equilibrium throughout the transport. In our previous work [Kirchberg et al., J. Phys. Chem. Lett. 11, 1729 (2020)], we have determined the nonequilibrium distribution of the solvent where its dynamics, expressed by a friction, is considered in two limiting regimes of fast and slow solvent relaxation. In dependence of the nonequilibrium solvent dynamics, we investigate now the electrical, thermal, and thermoelectric properties of the molecular junction. We show that by suitable tuning of the friction, we can reduce the heat dissipation into the solvent and enhance the heat transfer between the electrodes. Interestingly, we find that the Seebeck coefficient grows significantly by adapting the solvent friction in both regimes.

Molecular Picture of the Effect of Cosolvent Crowding on Ligand Binding and Dispersed Solvation Dynamics in G-Quadruplex DNA.

Understanding molecular interactions and dynamics of proteins and DNA in a cell-like crowded environment is crucial for predicting their functions within the cell. Noncanonical G-quadruplex DNA (GqDNA) structures adopt various topologies that were shown to be strongly affected by molecular crowding. However, it is unknown how such crowding affects the solvation dynamics in GqDNA. Here, we study the effect of cosolvent (acetonitrile) crowding on ligand (DAPI) solvation dynamics within human telomeric antiparallel GqDNA through direct comparison of time-resolved fluorescence Stokes shift (TRFSS) experiments and molecular dynamics (MD) simulations results. We show that ligand binding affinity to GqDNA is drastically affected by acetonitrile (ACN). Solvation dynamics probed by DAPI in GqDNA groove show dispersed dynamics from ∼100 fs to 10 ns in the absence and presence of 20% and 40% (v/v) ACN. The nature of dynamics remain similar in buffer and 20% ACN, although in 40% ACN, distinct dynamics is observed in <100 ps. MD simulations performed on GqDNA/DAPI complex reveal preferential solvation of ligand by ACN, particularly in 40% ACN. Simulated solvation time-correlation functions calculated from MD trajectories compare very well to the overall solvation dynamics of DAPI in GqDNA, observed in experiments. Linear response decomposition of simulated solvation correlation functions unfolds the origin of dispersed dynamics, showing that the slower dynamics is dominated by DNA-motion in the presence of ACN (and also by the ACN dynamics at higher concentration). However, water-DNA coupled motion controls the slow dynamics in the absence of ACN. Our data, thus, unravel a detailed molecular picture showing that though ACN crowding affect ligand binding affinity to GqDNA significantly, the overall dispersed solvation dynamics in GqDNA remain similar in the absence and the presence of 20% ACN, albeit with a small effect on the dynamics in the presence of 40% ACN due to preferential solvation of ligand by ACN.

Solvation dynamics of tetracyclic irbesartan in water and dichloromethane: Insights from local energy decomposition and ab initio molecular dynamics simulations library of the heterocyclic rings

Solvation energy changes Gibb’s energy when an ion or molecule is transferred from a vacuum to a solvent. Solvation is the attraction and association of molecules of a solvent with molecules or ions of a solute. Irbesartan is an angiotensin II receptor blocker used to treat hypertension and diabetic nephropathy alone or with other drugs. The central theme presented in this manuscript is the effect of explicit solvent on this drug. We optimized the molecules at the DFT/B3LYP cc-pVDZ level for Natural bond orbitals (NBO), noncovalent interactions (NCI), and wavefunction assay. Solvation energy and ab initio molecular dynamics were studied using PBE0-D3/def2-TZVP and energy decomposition analysis at DLPNO-CCSD(T). Fragmentation studies showed that Irbesartan can produce four fragments: biphenylmethan, butyl-, tetrazole, and diazaspironenone. NBO delocalisation energy of the molecule, and solvated complexes are found to be in the order irbesartan-DCM > irbesartan-water > irbesartan (for oxygen) and irbesartan-water > irbeasartan > irbesartan-DCM (at carbon) and irbesartan-DCM > irbesartan > irbesartan-water (at hydrogen). Noncovalent interactions in water and DCM at different pores showed significant interaction as evident from the binding energies. Ab initio molecular dynamics (AIMD) simulations proved that irbesartan-water pores are less stable than irbesartan-DCM. CPCM delivers solvated free energy and non-electrostatic free energy of irbesartan in water.

Intramolecular Charge Transfer of Curcumin and Solvation Dynamics of DMSO Probed by Time-Resolved Raman Spectroscopy.

Intramolecular charge transfer (ICT) of curcumin in dimethyl sulfoxide (DMSO) solution in the excited state was investigated by femtosecond electronic and vibrational spectroscopy. Excited-state Raman spectra of curcumin in the locally-excited and charge-transferred (CT) state of the S1 excited state were separated due to high temporal (<50 fs) and spectral (<10 cm−1) resolutions of femtosecond stimulated Raman spectroscopy. The ultrafast (0.6–0.8 ps) ICT and subsequent vibrational relaxation (6–9 ps) in the CT state were ubiquitously observed in the ground- and excited-state vibrational modes of the solute curcumin and the νCSC and νS=O modes of solvent DMSO. The ICT of curcumin in the excited state was preceded by the disruption of the solvation shells, including the breakage of hydrogen bonding between curcumin and DMSO molecules, which occurs at the ultrafast (20–50 fs) time scales.

Evolution of microscopic heterogeneity and dynamics in choline chloride-based deep eutectic solvents

Deep eutectic solvents (DESs) are an emerging class of non-aqueous solvents that are potentially scalable, easy to prepare and functionalize for many applications ranging from biomass processing to energy storage technologies. Predictive understanding of the fundamental correlations between local structure and macroscopic properties is needed to exploit the large design space and tunability of DESs for specific applications. Here, we employ a range of computational and experimental techniques that span length-scales from molecular to macroscopic and timescales from picoseconds to seconds to study the evolution of structure and dynamics in model DESs, namely Glyceline and Ethaline, starting from the parent compounds. We show that systematic addition of choline chloride leads to microscopic heterogeneities that alter the primary structural relaxation in glycerol and ethylene glycol and result in new dynamic modes that are strongly correlated to the macroscopic properties of the DES formed.

Impacts of Solvent and Alkyl Chain Length on the Lifetime of Singlet Cyclopentane-1,3-diyl Diradicaloids with π-Single Bonding.

The singlet 2,2-dialkoxycyclopentane-1,3-diyl diradicaloids are not only the important key intermediates in the process of bond homolysis but are also attracting attention as π-single bonding compounds. In the present study, the effects of solvent viscosity η (0.24-125.4 mPa s) and polarity π* (-0.11 to 1.00 kcal mol-1) on the reactivity of localized singlet diradicaloids were thoroughly investigated using 18 different solvents including binary mixed solvent systems containing ionic liquids. In low-η solvents (η < 1 mPa s), the lifetimes of singlet diradicaloids, which are determined by the rate constant for the isomerization of π-single-bonded singlet diradicaloids to the σ-bonded isomer, were substantially dependent on π*. Slower isomerization was observed in more polar solvents. In high-η solvents (η > 2 mPa s), the rate of isomerization was largely influenced by η in addition to π*. Slower isomerization was observed in more viscous solvents. Experimental results demonstrated the crucial roles of both solvent polarity and viscosity in the reactivity of singlet diradicaloids and thus clarified the characters of singlet diradicaloids and molecular motions during the chemical transformation. The dynamic solvent effect was further proved by a long alkyl chain introduced at a remote position of the reaction site.

Conformational and Solvation Dynamics of an Amyloidogenic Intrinsically Disordered Domain of a Melanosomal Protein.

The conformational plasticity of intrinsically disordered proteins (IDPs) allows them to adopt a range of conformational states that can be important for their biological functions. The driving force for the conformational preference of an IDP emanates from an intricate interplay between chain-chain and chain-solvent interactions. Using ultrafast femtosecond and picosecond time-resolved fluorescence measurements, we characterized the conformational and solvation dynamics around the N- and C-terminal segments of a disordered repeat domain of a melanosomal protein Pmel17 that forms functional amyloid responsible for melanin biosynthesis. Our time-resolved fluorescence anisotropy results revealed slight compaction and slower rotational dynamics around the amyloidogenic C-terminal segment when compared to the proline-rich N-terminal segment of the repeat domain. The compaction of the C-terminal region was also associated with the restrained mobility of hydration water as indicated by our solvation dynamics measurements. Our findings indicate that sequence-dependent chain-solvent interactions govern both the conformational and solvation dynamics that are crucial in directing the conversion of a highly dynamic IDP into an ordered amyloid assembly. Such an interplay of amino acid composition-dependent conformational and solvation dynamics might have important physicochemical consequences in specific water-protein, ion-protein, and protein-protein interactions involved in amyloid formation and phase transitions.