DMSO-water Mixtures Research Articles

Cosolvent Dimethyl Sulfoxide Influences Protein–Ligand Binding Kinetics via Solvent Viscosity Effects: Revealing the Success Rate of Complex Formation Following Diffusive Protein–Ligand Encounter

Protein-ligand-exchange kinetics determines the duration of biochemical signals and consequently plays an important role in drug design. Binding studies commonly require solubilization of designed ligands in solvents such as dimethyl sulfoxide (DMSO), resulting in residual amounts of DMSO following titration of solubilized ligands into aqueous protein samples. Therefore, it is critical to establish whether DMSO influences protein-ligand binding. Here, we address the general and indirect effect of DMSO on protein-ligand binding caused by solvent viscosity, which is strongly dependent on the relative concentrations of DMSO and water. As a model system, we studied the binding of a drug-like ligand to the carbohydrate recognition domain of galectin-3 in the presence of variable amounts of DMSO. We used isothermal titration calorimetry to characterize binding thermodynamics and 15N NMR relaxation to monitor kinetics. The binding enthalpy is not affected, but we observe a subtle trend of increasingly unfavorable entropy of binding, and consequently decreased affinity, with increasing DMSO concentration. The increasing concentration of DMSO results in a reduced association rate of binding, while the dissociation rate is less affected. The observed association rate is inversely proportional to the viscosity of the DMSO-water mixture, as expected from theory, but significantly reduced from the diffusion-controlled limit. By comparing the viscosity dependence of the observed association rate with that of the theoretical diffusion-controlled association rate, we estimate the success rate of productive complex formation following an initial encounter of proteins and ligands, showing that only one out of several hundred binding "attempts" are successful.

Dimethyl sulfoxide fosters larger micelles of docusate sodium in the mixed solutions with water

Docusate sodium also referred to as sodium bis(2-ethylhexyl)sulfosuccinate and dioctyl sulfosuccinate sodium (AOT) represents a green salt with proven potential across pharmacy, biology, and medicine. Physicochemical understanding of its inherent structural patterns, transport properties, and phase behavior in solutions is a challenging but essential endeavor. We hereby report conductometry, surface tension, density, and dynamic light scattering measurements of AOT in the dimethyl sulfoxide (DMSO)-water mixtures. The ab initio simulations are used to shed light on the electron density distributions and non-covalent interactions in the systems of our interest. We determine critical micelle concentration (CMC) and thermodynamic parameters of micellization (Gibbs free energy, enthalpy, and entropy) using the conductometry data at 298.15, 303.15, 308.15, 313.15, and 318.15 K. The CMC of AOT increases as DMSO mole fraction in the DMSO-water mixture increases. Negative free energies of micellization are observed over the entire investigated temperature range. Furthermore, higher contents of DMSO foster micellization gradually.The high contents of DMSO (X > 0.3) in the DMSO-water mixtures lead to abrupt changes in CMC and thermodynamics of AOT micellization. We link such changes to the formation of the DMSO self-associates and the associated structural changes in the liquid phase. The dynamic light scattering measurements reveal that larger micellar agglomerates and multilamellar AOT vesicles emerge at high DMSO fractions. The reported data fosters the thoughtful design of practically important systems in medicine.

Spectral characteristics of 3,5-diaminobenzoic acid in pure and mixed solvents: Experimental and theoretical study

The effect of solvents on the absorption and fluorescence (FL) spectra of 3,5-diaminobenzoic acid (DABA) was explored in pure solvents of diverse polarities and hydrogen bonding abilities. A bathochromic shift was observed in FL spectra while moving from non-polar to polar aprotic/protic solvents. The solvatochromic-based approaches showed that the dipole moment of DABA in the excited state (ES) is higher than its ground state (GS), which signifies that the ES is more polarized, corresponding to the GS. Moreover, the Catalan solvent polarity scale analysis suggested that the solvent acidity (SA) and dipolarity (SdP) influenced the absorption and FL spectra of DABA in solvents, signifying the presence of non-specific and specific interactions. The FL decay analysis in solvents was correlated with the observed steady-state results and suggested the presence of intramolecular charge transfer (ICT). The preferential solvation concept was utilized to understand the spectral variations of DABA in MeOH-water and DMSO-water mixtures. Further, the computational calculations utilizing the DFT (density functional theory) and TD-DFT (its time extension) for DABA were performed in the gas phase and solvents to estimate the electronic transitions and dipole moments. Furthermore, the natural bond orbital analysis and non-linear optical parameters were also obtained by DFT, and the findings revealed that ICT stabilizes the molecular system. Thus, DABA may have potential applications in the field of optoelectronics and fluorescence sensing.

N,O-bidentate BF2-enaminone complexes: Synthesis, electronic structure, photophysical properties, and biological behaviour

Twenty-six examples of 2,2-difluoro-3,6-diaryl-2,3-dihydro-1,3,2-oxazaborinines were synthesised at 42–98% yield from commercially available reagents with a set of simple procedures and were structurally fully characterised by 1H, 13C, 19F, and 11B NMR spectroscopy and single-crystal X-ray diffraction. Quantum chemical calculations at (Time-Dependent) Density Functional Theory ((TD)-DFT) level were performed to study structural and electronic properties of these new N,O-boron complexes with variable structures. A comprehensive experimental and computational investigation of the photophysical properties of these BF2-complexes showed that they are emissive in solutions and have a pronounced fluorescence in the solid state (up to 100%). They also demonstrated aggregation-induced emission enhancement (AIEE) effect, with a quantum yield up to 29%, blue–green-yellow emissions and good photostability. The dynamic light scattering (DLS) experiments confirmed the formation of nanoparticles in DMSO-water and EtOH-water mixtures. Confocal laser detection revealed that these BF2-complexes may penetrate living cells and accumulate in the endoplasmic reticulum.

Infrared spectroscopic analysis of hydrogen-bonding interactions in cryopreservation solutions

BackgroundIn this study we investigated hydrogen bonding interactions in hydrated and frozen solutions of different cryoprotective agents (CPAs) including dimethyl sulfoxide, glycerol, ethylene glycol, propylene glycol, and trehalose. We also investigated the effect of CPAs on ice crystal growth during storage and correlated this with storage stability of liposomes. MethodsFTIR spectroscopy was used to study hydrogen bonding interactions in CPA solutions in H2O and D2O, and their thermal response was analyzed using van ’t Hoff analysis. The effect of CPAs on ice crystal growth during storage was investigated by microscopy and correlated with storage stability of liposomes encapsulated with a fluorescent dye. ResultsPrincipal component analyses demonstrated that different CPAs can be recognized based on the shape of the OD band region only. Chemically similar molecules such as glycerol and ethylene glycol closely group together in a principal component score plot, whereas trehalose and DMSO appear as condensed separated clusters. The OH/OD band of CPA solutions exhibits an overall shift to higher wavenumbers with increasing temperature and changed fractions of weak and strong hydrogen interactions. CPAs diminish ice crystal formation in frozen samples during storage and minimize liposome leakage during freezing but cannot prevent leakage during frozen storage. ConclusionsCPAs can be distinguished from one another based on the hydrogen bonding network that is formed in solution. DMSO-water mixtures behave anomalous compared to other CPAs that have OH groups. CPAs modulate ice crystal formation during frozen storage but cannot prevent liposome leakage during frozen storage.

Delamination by Repulsive Osmotic Swelling of Synthetic Na-Hectorite with Variable Charge in Binary Dimethyl Sulfoxide-Water Mixtures.

Swelling of clays is hampered by increasing layer charge. With vermiculite-type layer charge densities, crystalline swelling is limited to the two-layer hydrate, while osmotic swelling requires ion exchange with bulky and hydrophilic organic molecules or with Li+ cations to trigger repulsive osmotic swelling. Here, we report on surprising and counterintuitive osmotic swelling behavior of a vermiculite-type synthetic clay [Na0.7]inter[Mg2.3Li0.7]oct[Si4]tetO10F2 in mixtures of water and dimethyl sulfoxide (DMSO). Although swelling in pure water is restricted to crystalline swelling, with the addition of DMSO, osmotic swelling sets in at some threshold composition. Finally, when the DMSO concentration is increased further to 75 vol %, swelling is restricted again to crystalline swelling as expected. Repulsive osmotic swelling thus is observed in a narrow composition range of the binary water-DMSO mixture, where a freezing point suppression is observed. This suppression is related to DMSO and water molecules exhibiting strong interactions leading to stable molecular clusters. Based on this phenomenological observation, we hypothesize that the unexpected swelling behavior might be related to the formation of different complexes of interlayer cations being formed at different compositions. Powder X-ray diffraction and 23Na magic angle spinning-NMR evidence is presented that supports this hypothesis. We propose that the synergistic solvation of the interlayer sodium at favorable compositions exerts a steric pressure by the complexes formed in the interlayer. Concomitantly, the basal spacing is increased to a level, where entropic contributions of interlayer species lead to a spontaneous thermodynamically allowed one-dimensional dissolution of the clay stack.

Effect of solvents and glutathione on the decomposition of the nitrosyl iron complex with N-ethylthiourea ligands: An experimental and theoretical study

Dinitrosyl iron complexes (DNICs) are a depot and potential source of free NO in organisms. Their synthetic analog, N-ethylthiourea DNIC [Fe(SC(NH2)(NHC2H5))2(NO)2]+Cl−∙[Fe(SC(NH2)(NHC2H5))Cl(NO)2]0 (complex 1), as cardioprotective and cytostatic agent is a promising prodrug for the treatment of socially relevant diseases. In this work, transformation mechanism of complex 1 has been studied in anaerobic aqueous solution (pH = 7.0), DMSO, and ethanol. It was shown that the solvent has a significant effect on the decomposition of complex. According to EPR-spectroscopy, only cationic part of complex is found upon its dissolution in water; only neutral part is retained in DMSO, and both fragments are present in ethanol. Effective generation of NO occurs in an aqueous solution. The structures of the decomposition products were proposed for all solvents, their UV-spectra and rate constants were calculated. From the experimental and theoretical data obtained, it follows that complex 1 is most stable in DMSO. Solutions of complex in a DMSO-water mixture can be used to improve its bioavailability in further in vitro and in vivo studies. Also, we have analyzed its interaction with glutathione (GSH), which can participate in the metabolism of this compound. This study shows that complex 1 reacts with GSH to form a new binuclear DNIC with two GS−-ligands. It was found that the resulting complex is a more prolonged NO-donor than the initial one: k = 6.1∙10−3·s−1 in buffer, k = 6.4∙10−5 s−1 with GSH. This reaction may prevent S-glutathionylation of the essential enzyme systems and is important for metabolism of complex, associated with its antitumor activity.

A benzoxazole-based smart molecule for relay detection of zinc and phosphate ions and its implication towards molecular logic gate constructions

A benzoxazole-based fluorescent chemosensor (OPMP) has been designed, synthesized, and characterized by various analytical techniques. The as-prepared OPMP is employed for the cascade detection of Zn2+ and PO43- ions, respectively, based on the ‘off–on-off’ photoluminescence mechanism in 30% (v/v) water-DMSO mixture. A significant fluorescence enhancement of OPMP at 495 nm is observed due to chelation-enhanced fluorescence upon binding with Zn2+ ions. A visual bluish-green color could be seen under 365 nm UV light irradiation, which is also well supported by the color chromaticity diagram. The fluorescence of the Zn2+chelated OPMP complex is quenched in the presence of PO43- ions. The sensitivity of OPMP and Zn2+chelated OPMP complex towards detection of Zn2+ and PO43- ions can be possible down to 38 nM and 48 nM, respectively. Such as dual ions detection system with outstanding reversibility and reproducibility led us to consider our OPMP as a feasible candidate for the construction of molecular logic circuits, molecular keypad locks, and set-reset memorized molecular devices. Further, an OPMP staining paper strips-based test kit has been fabricated and demonstrated for the sequential detection of Zn2+ and PO43- ions, respectively.

Hydrogen bonding structure and dynamics of cis- and trans- conformers of N-methylformamide in water, DMSO and water-DMSO mixtures at varying compositions

The local hydrogen bonding structure and dynamics of cis- and trans- N-methylformamide (NMF) in water, DMSO and in water–DMSO mixture is investigated by classical molecular dynamics simulations. We have considered five different concentrations of NMF in water as well as in DMSO at 298 K. In the case of NMF (XNMF = 0.20) in water–DMSO mixtures, we have considered six different concentrations, varying from NMF in pure water to DMSO. It is observed that the donating ability of amide–hydrogen of NMF to the oxygen of DMSO is higher compared to the oxygen of water. The variation of DMSO shows negligible effects on the HNMF…ODMSO radial distribution function (RDF), whereas the HNMF…OWAT decreases with the addition of water to the solution. In the case of NMF in water–DMSO mixtures, the addition of DMSO strengthens the HNMF…ODMSO as well as HNMF…OWAT correlation, but it differently affects for cis- and trans- NMF in the solution. DMSO prefers cis- conformer, whereas water prefers trans- NMF. In NMF–water–DMSO mixtures, the addition of DMSO strengthens HWAT…ONMF up to intermediate DMSO concentration, but at very high DMSO concentration, it decreases due to preferable HNMF…ODMSO interaction. The probability of hydrogen bonding between NMF–NMF is higher in NMF–DMSO solution compared to NMF–water. The dynamical slowdown is observed for all the species in water–NMF mixtures at intermediate concentration, whereas in the case of NMF–DMSO solution, faster dynamics are observed with the addition of DMSO. For NMF in water–DMSO mixtures, the dynamical slowdown is observed as DMSO is added to the NMF–water solution. Our calculated hydrogen-bond lifetime suggested that the DMSO forms a stronger hydrogen bond with cis-NMF whereas water generally prefers trans-NMF.

Elucidation of molecular interactions between sugar alcohol and dimethyl sulfoxide in aqueous system: Volumetric and acoustic study

Sugar alcohols have a significant role in the pharmaceutical and food industry due to their dominant effect on blood glucose levels and as artificial sweeteners in dairy products. The volumetric and acoustic study of sugar alcohol is the easiest way to characterize the solvation behavior that is in demand to get better considerations about mechanisms of sweet taste chemoreception and give valuable information about protein stabilization, and solute–solvent interactions. Densities and sound speeds of meso-erythritol in water and water-DMSO mixtures were measured at 293.15 K, 298.15 K, 303.15 K, 308.15 K, and 313.15 K under ambient pressure. The experimental data was further used to calculate the apparent molar volume, apparent molar volume at infinite dilution, partial molar volume transfer (Δt∅Vo), apparent specific volume, expansibility, and compressibility to evaluate the solvation behavior and taste quality of investigated mixtures of meso-erythritol in an aqueous DMSO system. Apparent specific volume values i.e. 0.51–0.71 cm3/g can predict the taste quality which is consistent with their ability to evoke a pure sweet taste. Positive values of Hepler’s constant (∂2∅vo /∂T2) represent structure making capability of meso-erythritol in water and aqueous DMSO. The obtained parameters were used to get the different mixing effects due to the interactions between meso-erythritol in water and in aqueous DMSO solutions that characterize the hydration properties and solvation behavior of sugar alcohol.

Unique phase behaviour and self-assembly of a lysine derivative, Fmoc-homoarginine, in water-DMSO mixtures.

Ternary solutions of an amino acid derivative, Fmoc-homoarginine (Fmoc-hArg), dimethylsulfoxide (DMSO), and water exhibit unique phase behaviour. Fmoc-hArg is dissolved in DMSO to provide a clear solution, but the solution becomes turbid after aging (turn-over phase separation). The turbid DMSO solution of Fmoc-hArg becomes clear by addition of water at a volume fraction of water in the DMSO-water mixture from 0.2 to 0.4, and turbid again at . Concentrated-phase droplets in the turbid solutions at act as centers of spherulite and needle-like crystal formation. This unique phase behaviour is explained theoretically on the basis of the competition between the micellization and phase separation and the Flory-Huggins theory.

STUDY OF ELECTRICAL PROPERTIES AND SOLVENT BEHAVIOUR OF 6-(4-CHLOROPHENYL)-1, 2, 3, 4- TETRAHYDRO-4-OXO-2-THIOXOPYRIMIDINE-5- CARBONITRILE AT DIFFERENT TEMPERATURES

Conductance has been measured in 60% DMSO-water mixture at various concentration in the temperature range 298-313K. The limiting molar conductance (λ0m), degree of dissociation (α), dissociation constant (Kd), Walden constant, energy of activation and thermodynamic parameters are evaluated. The results obtained have been interpreted in terms of molecular interactions and solvent properties.

Apparent molar volume anomaly in water-dimethyl sulfoxide liquid mixtures. Molecular dynamics computer simulations

We have studied the composition dependence of density of liquid water-DMSO mixtures at different temperatures by using the isobaric-isothermal (NPT) molecular dynamics computer simulations. The non-polarizable semi-flexible, P1 and P2 models for the DMSO molecule combined with the TIP4P-2005 water model are considered. The excess mixing volume and the apparent molar volumes of the species are reported. We have established that the P1-TIP4P-2005 model for the mixture provides a very good description of the location of the minimum of apparent molar volume for DMSO species indicating the anomaly. Most important is that the temperature interval where the hydrophobic effect exists, is correctly captured with this modelling, in contrast to the P2-TIP4P-2005 model.

Revisiting the composition dependence of the properties of water-dimethyl sulfoxide liquid mixtures. Molecular dynamics computer simulations

We have revisited the composition dependence of principal properties of liquid water-DMSO mixtures by using the isobaric-isothermal molecular dynamics computer simulations. A set of non-polarizable semi-flexible models for the DMSO molecule combined with the TIP4P-2005 and TIP4P/ε water models is considered. We restrict calculations to atmospheric pressure, 0.1013 MPa, and room temperature, 298.15 K. Composition trends of density, excess mixing volume and excess mixing enthalpy, partial molar volumes and partial molar enthalpies of species, apparent molar volumes are reported. Besides, we explore composition trends of the self-diffusion of species, the static dielectric constant and the surface tension. Evolution of the microscopic structure of the mixture with composition is analyzed in terms of radial distributions functions, coordination numbers and the fractions of hydrogen-bonded molecules. We intend to capture the peculiarities of mixing the species in the mixture upon the DMSO molar fraction and the anomalous behaviors, if manifested in each of the properties under study. The quality of several combinations of the models for species is evaluated in detail to establish the possibility of necessary improvements.

Novel Y-shaped AIEE-TICT active π-extended quinoxalines-based donor–acceptor molecules displaying acidofluorochromism and temperature dependent emission

Seven novel donor–acceptor-donor type push–pull quadrupolar quinoxaline scaffolds exhibiting blue or green emission in solution were synthesised in good yields by Heck coupling reaction. The photophysical properties of these quinoxaline derivatives were tuned by introducing functional groups of varying electronic nature on the quinoxaline moiety. Mega Stokes shifts and large bathochromic shifts in emission wavelength were observed on moving from non-polar toluene to polar DMSO. A twisted structural conformation and donor–acceptor interactions along with herringbone arrangement were revealed by single crystal XRD studies. “on–off-on” fluorescence switching was observed upon increasing water fraction in DMSO-water mixture. A reversible switching in colour and emission properties upon treatment with TFA and TEA in both solution and solid state was also observed which was utilised for the fabrication of filter paper strips for the detection of volatile acids. These compounds also displayed linear dependence of emission maxima on temperature.

Understanding the Effect of Solvent Environment on the Interaction of Hydronium Ion with Biomass Derived Species: A Molecular Dynamics and Metadynamics Investigation.

The addition of aprotic solvents results in higher reactivities and selectivities in many key aqueous phase biomass reactions, including the acid-catalyzed conversion of fructose to 5-hydroxyl methyl furfural (HMF). The addition of certain co-solvents inhibits the formation of humins via preferential solvation of key functional groups and can alter reaction kinetics. An important factor in this context is the relative stability of the hydronium ion (the catalyst) in the vicinity of the biomass moiety as compared to that in bulk, as it could determine its efficacy in the protonation step. Hence, in the present work, molecular dynamics (MD) simulations of HMF (the model product) and fructose (the model reactant) in acidic water and water-DMSO mixtures are performed to analyze their interaction with the hydronium ions. We show that the presence of DMSO favors the interaction of the hydronium ion with fructose, whereas it has a detrimental effect on the interaction of hydronium ion with HMF. Well-tempered metadynamics (WT-MTD) simulations are performed to determine the relative stability of the hydronium ion in the immediate vicinity of fructose and HMF, as compared to that in the bulk solvent phase, as a function of solvent composition. We find that DMSO improves the stabilization of the hydronium ions in the first solvation shell of fructose compared to that in the bulk solvent. On the other hand, hydronium ions become less stable in the immediate vicinity of HMF, as the concentration of DMSO increases.

Liquid-liquid phase separation and self-assembly of a lysine derivative Fmoc-L-lysine in water-DMSO mixtures

Liquid-liquid phase separation and self-assembly of a lysine derivative Fmoc-L-lysine in water-DMSO mixtures

Solvent-controlled intramolecular excimer emission from organosilicon derivatives of naphthalene

New mono-, bis- and tetra-fluorophoric organosilicon naphthalene derivatives, that are able to form intramolecular excimers have been synthesized and characterized. The synthesized compounds show only monomeric fluorescence in dilute solutions of common organic solvents, but exhibit relatively strong excimer-like emission in DMSO-water and THF-water mixtures. In all cases, the intensity of excimer fluorescence increases with increasing water content and decreases with increasing temperature. Fully and partially overlapping excimer conformations have been modeled by DFT-based calculations. Properties of different intramolecular excimers in an ensemble of four naphthalene molecules linked to a cyclotetrasiloxane ring in an all-cis arrangement are considered.

Viscometric study of metformin complexes with some transition metal ions at different temperatures

The measurement of densities, specific viscosities of metformin drugs complexes with some transition metal ions at different concentration in the range (1 x10−2 M to 6 x10−4 M) in 70% (DMSO + water) solvent at 303K are reported. The experimental data shows, the effect of concentration of solute on viscosity in DMSO-water mixtures which gives idea about the molecular interactions present in different solutions. Appreciable molecular interactions were observed between the metal complexes of metformin and binary mixture. The thermodynamic properties such as free energy change (ΔG), enthalpy change (ΔH) and entropy change (ΔS) of metal complexes of metformin drugs were analyzed in 70% (DMSO + water) mixture at different temperature such as 308 K, 313 K and 318 K. The experimental data gives the idea about effect of temperature on the molecular interaction and structural changes in solute.

Calorimetric observation of lysozyme degradation at elevated temperature in water and DMSO-water mixtures

The reversibility of protein denaturation is an essential factor for biotechnology. Previous differential scanning calorimetry (DSC) studies demonstrated the development of the low-temperature shoulder on the calorimetric denaturation peak of lysozyme in successive heating-cooling cycles, which implies irreversible denaturation. However, this effect was not thoroughly investigated. In the present work, we have quantitatively studied the effect of incubation at the elevated temperature on the state of lysozyme in water and mixtures of water with dimethyl sulfoxide (DMSO) using DSC. The changes to the state of the lysozyme molecule indicated by DSC thermograms were also evaluated by circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS) techniques. It is noted that with the increase of duration or temperature of incubation, the low-temperature peak on DSC thermograms grows, while the height of the unfolding peak of native structure decreases. The increase in the height of the low-temperature peak in DSC scans correlates with the development of the sideband associated with the absorption of the carboxyl group in the infrared spectra. This result suggests that the low-temperature endothermic peak corresponds to the unfolding of the deamidated protein. At the same time, DLS measurements indicate absence of aggregation, while FTIR and CD data demonstrate that deamidated protein maintains a native-like structure. The evaluation of the DSC thermograms allowed to determine the rates and activation energy of the degradation of protein molecules at the elevated temperatures. The addition of DMSO slows down the protein degradation but has little effect on the apparent activation energy of the process.