Aqueous Solutions Of N-methylacetamide Research Articles

Complex investigation of H-bond in Water-N-methylacetamide system: Volumetric properties, DFT, IR, MD analysis

• Behavior of the volumetric properties of the binary water-NMA mixture was studied over wide pressure ranges. • Hydrogen bonds in NMA–water mixtures were analyzed using computer chemistry and vibrational spectroscopy. • The analysis of the strength of the hydrogen bond between amides and surrounding water molecules is carried out. • The hydrogen atoms of water and amide compete as hydrogen bond donors. A combined approach of computational chemistry, vibrational spectroscopy experiments, and density measurements was used to study the structural properties of water-N-methylacetamide mixtures over the entire concentration range. The structure of N-methylacetamide dimers and hydrogen-bonded complexes of N-methylacetamide with water molecules was investigated by the quantum chemical method on the basis of the density functional theory. The vibrational spectra of aqueous solutions of N-methylacetamide were recorded. Based on quantum chemical calculations, the bands of the vibrational spectrum were identified, which made it possible to trace the change in hydrogen bonding in the system. At increased N-methylacetamide concentration, the hydrogen bond network rearranges. The number of hydrogen bonds between water molecules decreases, water molecules bind to N-methylacetamide molecules, changing the nature of its environment. Aqueous mixture containing N-methylacetamide shows strong deviations of volumetric properties from ideality. For the further analysis of the data obtained, molecular dynamics simulation of this system was conducted at various temperatures and pressures. It was shown that the resulting hydrogen bonds are of medium strength, but their strength depends on the water molecule environment, which is proved by NBO and QTAIM data. A network of hydrogen bonds is formed in N-methylacetamide aqueous solution, which is noticeably destroyed with an increase in temperature and slightly changes with an increase in pressure.

Understanding the interactions between protein stabilizers and the peptide bond through the analysis of the volumetric and compressibility properties for the model systems

This work confirms our earlier supposition, that volumetric and acoustic parameters for simple model proposed by us are directly related to stabilizing/destabilizing effect of osmolytes on proteins structure. The apparent molar volumes, VΦ, and the apparent molar isentropic compressions, KS, Φ, of glycine and N,N,N –trimethylglycine (betaine) were determined from densities and speed of sound measurements in aqueous solution of N-methylacetamide (as a model of peptide bond of protein). The standard molar parameters for osmolytes were obtained from concentration dependence of the calculated quantities at NMA concentration equal 2, 4, 6 and 8 (mol/kg) and at temperature T = (288.15, 298.15 and 308.15) K. The standard values were combined with volumetric and compressibility data for amino acids in pure water to obtain transfer properties from water to aqueous N-methylacetamide solutions. The standard partial molar volume of transfer of studied osmolytes, ΔtVΦ0, seems to be related mainly to hydrophilic/hydrophobic features of molecules. The stabilizing/destabilizing effect of solute on protein structure is reflected in temperature influence on the limiting partial molar quantities.

Pressure–Volume–Temperature Relationships for Aqueous Solutions of N-Methylacetamide at Temperatures Ranging from 278.15 to 323.15 K and Pressures up to 100 MPa

This paper deals with the densities of aqueous solutions of N-methylacetamide (NMA) in the range of concentrations x (starting from 0.0095 to 0.699) at T = 278.15, 288.15, 298.15, 308.15, 323.15, a...

Density measurements of water – N-methylacetamide mixture at temperatures from 274.15 to 333.15 K and ambient pressure. A comparison of the volumetric characteristics of some amides

The densities ρ of the binary mixture of N-methylacetamide with water have been measured in the entire composition range of the mixture liquid state at T = (278.15, 288.15, 298.15, 308.15, 323.15 and 333.15) K at atmospheric pressure (0.1 MPa). The densities were also measured for dilute aqueous solutions of N-methylacetamide (from 0.00455 to 0.05743 mol fractions) at a temperature from 274.15 to 283.15 K, with an increment of 1 K at atmospheric pressure, in order to study the effect of N-methylacetamide on the temperature of the maximum water density. These data were later used to calculate the excess molar volumes .VmE., partial molar volumes of water V1 and N-methylacetamide V2, and to obtain the limiting partial molar volumes Vi∞ and limiting partial molar isobaric expansion of N-methylacetamide EP,2∞. The following volumetric characteristics were then obtained from these values: the shift temperature of the maximum density, Hepler’s constant, the pressure derivative of the second virial coefficient, relative volumetric parameter of hydration. The obtained parameters show the effect of N-methylacetamide on water. The study also included a comparison of these volumetric characteristics for several aqueous solutions of amides: acetamide, urea and N-methylurea. The paper also presents a comparison of these parameters at the changes in the structure of amide molecules.

The interaction parameters for solutions of n-butylurea in aqueous solutions of N-methylacetamide – The volumetric and compressibility studies between 288.15 K and 308.15 K

Densities and speed of sound were measured for solutions of n-butylurea in aqueous solution of N-methylacetamide 2, 4, 6 and 8 (mol/kg) at T = (288.15, 298.15 and 308.15) K. From these data the apparent molar volumes, VΦ, the apparent molar isentropic compressions, KS, Φ, of the solute were determined. The concentration dependencies of the calculated quantities have been used to obtain the standard partial molar parameters. The latter values were combined with the previously published volumetric and compressibility data for n-butylurea in pure water to obtain the partial molar properties of transfer from water to aqueous N-methylacetamide solutions. These parameters were used to determine the interaction parameters according to the McMillan-Mayer theory. The calculated parameters and their temperature characteristics are discussed in terms of solute–solvent, solute–solute and solute–cosolute interactions.

The hydration properties of protein stabilizer, trimethylamine-N-oxide in aqueous solutions of N-methylacetamide—The volumetric and compressibility studies between 288.15 and 308.15 K

Apparent molar volumes, VΦ, and apparent molar isentropic compressions, KS,Φ, of the protein stabilizer, trimethylamine-N-oxide (TMAO) were determined from the densities and speed of sound measured at T = (288.15, 298.15 and 308.15) K in aqueous solutions of N-methylacetamide (NMA) at four different concentrations (2, 4, 6 and 8 mol/kg). The concentration dependencies of the calculated quantities extrapolated to the infinite dilution lead to the standard partial molar properties. The latter values were combined with the previously published data for TMAO in pure water, to obtain the partial molar properties of transfer from water to aqueous NMA solutions. From the transfer data the interaction parameters were determined according to the McMillan-Mayer theory formalism. The calculated parameters and their temperature characteristics are discussed in terms of solute-solvent, solute-solute and solute-cosolute interactions and compared with analogous data for protein denaturant, n-butylurea.

Aqueous solutions of NMA, Na2HPO4, and NaH2PO4 as models for interaction studies in phosphate–protein systems

Phosphate buffers are essential for many areas of studies. However, their influence on buffered systems is often ignored. The phosphate salts can interact with biologically important macromolecules (e.g. proteins) and stabilize or destabilize them. With our research, we want to answer question what kind of interactions, if any, occur between phosphate ions and a protein backbone model — N-methylacetamide (NMA). ATR-FTIR spectroscopy in the amide I range and in the regions characteristic for PO vibrations provides information on direct and indirect (water-mediated) interactions. The analysis is supported by chemometric, DFT, and QTAIM calculations. Our results indicate that direct NMA–phosphate ion interactions are quite rare and indirect. Water molecules seem to play an important role in such systems. The model studies indicate that no preferential interactions between NMA and phosphate ions in solutions are formed, and may imply that such interactions are also unfavorable in protein-based systems.

Hydrophobic Collapse in N-Methylacetamide-Water Mixtures.

Aqueous N-methylacetamide solutions were investigated by polarization-resolved pump–probe and 2D infrared spectroscopy (2D IR), using the amide I mode as a reporter. The 2D IR results are compared with molecular dynamics simulations and spectral calculations to gain insight into the molecular structures in the mixture. N-Methylacetamide and water molecules tend to form clusters with “frozen” amide I dynamics. This is driven by a hydrophobic collapse as the methyl groups of the N-methylacetamide molecules cluster in the presence of water. Since the studied system can be considered as a simplified model for the backbone of proteins, the present study forms a convenient basis for understanding the structural and vibrational dynamics in proteins. It is particularly interesting to find out that a hydrophobic collapse as the one driving protein folding is observed in such a simple system.

Behaviour of aqueous N-methylacetamide solution in presence of ethanol and 2,2,2 tri-fluoroethanol: Hydrogen bonding structure and dynamics

Effects of ethanol (EtOH) and 2,2,2-trifluoroethanol (TFE) on the hydrogen bonding structure and dynamics in aqueous N-methylacetamide (NMA) solution are investigated by classical molecular dynamics simulations. The interactions between NMA and water in presence of ethanol or 2,2,2-trifluoroethanol molecules are depicted here by different site-site radial distribution functions and the average interaction energies between these species in the solution. It is observed that the aqueous peptide hydrogen bond interaction is preferably stronger with increasing alcohol concentration in the solution, whereas hydrophobic solvation of CH3-groups of NMA decreases significantly. The ONMA…HNMA hydrogen-bond interaction is better maintained in TFE solution than in EtOH. TFE prefers to donate the hydrogen-bond towards water or NMA, whereas EtOH shows the hydrogen bond accepting ability. The lifetimes of NMA-water, water-water hydrogen bonds are found to increase with alcohol concentration in the solution and it is more significant in case of EtOH than TFE. Our calculated self-diffusion coefficients and orientational relaxation times shows slower dynamics of water in concentrated EtOH solution compared to TFE due to formation of preferable water-ethanol hydrogen bonds.

Aqueous N-methylacetamide: New analytic potentials and a molecular dynamics study

Recently formulated intermolecular potentials for the N-methylacetamide-water system have been used to model the hydrogen-bond like interactions in classical molecular dynamics (MD) simulations of aqueous solutions of N-methylacetamide (NMA). The MD calculations have been performed covering a wide concentration range at a temperature of 308K, in order to validate the model potential through the reproduction of structural and dynamical properties of liquid NMA. The analytic intermolecular potential energy surface (PES), obtained by decomposing the involved molecules into a number of interacting centers, is represented as sum of van der Waals and electrostatic pair interaction terms. The van der Waals terms contain parameters directly connected to physical observables, such as atomic and bond polarizabilities, and can be easily optimized in order to embody more collective contributions such as hydrogen bonding like interactions. The parametrization is flexible enough to correctly match the electrostatic contributions, reproducing the results on N-methylacetamide solutions, as available from previous studies based on dynamics simulations and ab initio calculations. The use of the PES, combined with classical trajectories, provides a computationally effective alternative to ab initio MD simulations, widely used to simulate similar systems. Moreover, the characterization of the interacting centers is portable to different molecular environments, so that the PES can be extended for perspective applications to larger molecular systems and biomolecules.

Effects of trimethylamine-N-oxide (TMAO) on aqueous N-methylacetamide solution: A comparison of different force fields of TMAO

We have performed the molecular dynamics simulations study to investigate the interaction of different force-field parameters of trimethylamine-N-oxide (TMAO) with aqueous solution of N-methylacetamide (NMA). We have calculated the number and energies of NMA-water, water-water and TMAO-water hydrogen bonds along with their hydrogen-bond lifetime, and structural relaxation times at varying concentrations of TMAO for three different force-fields. Our analysis indicates that compared to widely used Kast's model, other recently developed models strengthen the water-TMAO interaction. Since the TMAO force fields of Garcia and co-workers, and Netz and co-workers change the interaction behavior between the species in solution, it is expected that the observed translational, rotational and hydrogen bond properties will be changed accordingly. Our observations suggest that TMAO prefers to interact with NMA atomic sites through its methyl groups whereas hydrogen bonding interactions between oxygen atom of TMAO and amide-hydrogen of NMA (OTMAO…HNMA) also have a significant role which is more prominent in TMAO models of Garcia and Netz as compared to Kast's model. The hydrogen bond stability between oxygen of TMAO and hydrogen of water (OTMAO…HW) is overestimated by Netz and co-workers as compared with Kast and Garcia's models of TMAO.

Effects of dimethyl sulfoxide on the hydrogen bonding structure and dynamics of aqueous N-methylacetamide solution

Effects of dimethyl-sulfoxide (DMSO) on the hydrogen bonding structure and dynamics in aqueous N-methylacetamide (NMA) solution are investigated by classical molecular dynamics simulations. The modifications of structure and interaction between water and NMA in presence of DMSO molecules are calculated by various site-site radial distribution functions and average interaction energies between these species in the solution. It is observed that the aqueous peptide hydrogen bond interaction is relatively stronger with increasing concentration of DMSO, whereas methyl-methyl interaction between NMA and DMSO decreases significantly. The DMSO molecule prefers to interact with amide-hydrogen of NMA even at lower DMSO concentration. The lifetimes and structural-relaxation times of NMA-water, water-water and DMSO-water hydrogen bonds are found to increase with increasing DMSO concentration in the solution. The slower translational and rotational dynamics of NMA is observed in concentrated DMSO solution due to formation of stronger inter-species hydrogen bonds in the solution. Classical molecular dynamics simulations have been carried out to investigate the influence of DMSO on the structure and dynamics of hydrogen bonds in aqueous NMA solutions. Properties like inter-species average interaction energies, self-diffusion coefficients, orientational relaxation times as well as hydrogen bond structural relaxation times and lifetimes have been calculated.

A Comparative Study on the Aggregation and Thermodynamic Properties of Anionic Sodium Dodecylsulphate and Cationic Cetyltrimethylammonium Bromide in Aqueous Medium: Effect of the Co‐solvent N‐Methylacetamide

AbstractThe effect of co‐solvent N‐methylacetamide (NMA) (0.035, 0.046, 0.127, and 0.258 mol kg−1) on the micellization behaviour of anionic surfactant sodium dodecylsulphate (SDS) (3.21–10.35 mmol kg−1) and cationic surfactant cetyltrimethylammonium bromide (CTAB) (0.19–3.72 mmol kg−1) in aqueous solution was explored by employing conductivity measurements at different temperatures (298.15–313.15 K). The critical micelle concentration (CMC) values for SDS and CTAB in aqueous solutions of NMA were determined from the conductivity versus surfactant concentration plots. The variations in the CMC values of SDS with NMA concentration are in striking contrast to those observed in the case of CTAB. The various relevant thermodynamic parameters of micellization, viz. standard enthalpy change, ΔHmo, standard entropy change, ΔSmo, and standard Gibbs free energy change, ΔGmo, were determined using the temperature variation of the CMC values and counterion binding. The results not only relate these thermodynamic parameters to the consequences of intermolecular interactions but are also able to differentiate between SDS–water–NMA and CTAB–water–NMA systems in terms of contributions from head groups as well as alkyl chains of surfactants.

First-Principles Simulation Study of Vibrational Spectral Diffusion and Hydrogen Bond Fluctuations in Aqueous Solution of N-Methylacetamide.

We have presented a first-principles simulation study of the vibrational spectral diffusion and hydrogen bond dynamics in an aqueous solution of N-methylacetamide (NMA). We have studied the spectral diffusion of local OD stretch modes of deuterated water in the first hydration shells of the carbonyl (CO) and deuterated amide (ND) modes and their relations to the dynamics of hydrogen bonds formed by water with these groups. The frequency fluctuations of the amide I and amide A modes of the solute are also investigated. It is found that the vibrational spectral diffusion of water molecules in the first hydration shell of the carbonyl oxygen of NMA proceeds with three time scales: A short-time relaxation (∼100 fs) originating from the dynamics of NMA-water hydrogen bonds without breaking, a slower relaxation (∼3.3 ps) arising from the breaking dynamics of NMA(CO)-water hydrogen bonds, and another longer time constant (∼14 ps) coming from the escape dynamics of water from the first hydration shell of carbonyl oxygen. The current results show that the NMA(CO)-water hydrogen bonds have a longer lifetime than those between water molecules, although frequency calculations reveal a slightly higher stretch frequency of the water molecules in the first hydration shell of the carbonyl oxygen of NMA. An analysis of the vibrational spectral diffusion of solute modes is also presented in terms of the dynamics of solute-water hydrogen bonds. Effects of dispersion interactions on various calculated properties of the NMA-water system are also investigated in the present work.

Effects of co-solutes on the hydrogen bonding structure and dynamics in aqueous N-methylacetamide solution: a molecular dynamics simulations study

The effects of trimethylamine-N-oxide (TMAO), urea and tetramethyl urea (TMU) on the hydrogen bonding structure and dynamics of aqueous solution of N-methylacetamide (NMA) are investigated by classical molecular dynamics simulations. The modification of the water's hydrogen bonding structure and interactions is calculated in presence of these co-solutes. It is observed that the number of four-hydrogen-bonded water molecules in the solution decreases significantly in the presence of TMAO rather than urea and TMU. The lifetime and structural relaxation time of water–water and NMA–water hydrogen bonds show a strong increase with the addition of TMAO and TMU in the solution, whereas the change is nominal in case of urea solution. It is also found that the translational and rotational dynamics of water and NMA slowdown with increasing the concentration of these osmolytes. The slower dynamics of water and NMA is more pronounced in case of TMAO and TMU solution, as these co-solutes strengthen the average hydrogen bond energies between water–water and NMA–water, whereas urea has a little effect on the hydrogen bonding structure and dynamics of aqueous NMA solution. The calculated self-diffusion coefficient values for water and these co-solutes are in similar pattern with experimental observations.

Effects of methanol on the hydrogen bonding structure and dynamics in aqueous N-methylacetamide solution

The effect of methanol on the hydrogen bonding structure and dynamics in aqueous solution of N-methylacetamide (NMA) is investigated by classical molecular dynamics simulations. The modifications of structure and interaction between water and NMA in presence of methanol are calculated by different site–site radial distribution functions and average interaction energies between these species in the solution. It is observed that the methyl–methyl interaction between NMA and methanol prefers even at lower methanol concentration. The slower translational and rotational dynamics of NMA is observed in water–methanol mixtures as it is found for both water and methanol in the mixtures. The lifetime and structural-relaxation time of NMA–water and NMA–methanol hydrogen bonds show a strong increase with addition of methanol in the solution, whereas the change is not linearly dependent on concentration. It is also found that the lifetime of water–water and water–methanol hydrogen bond increases with increasing methanol concentration in the solution.

Kirkwood-Buff analysis of aqueous N-methylacetamide and acetamide solutions modeled by the CHARMM additive and Drude polarizable force fields.

Kirkwood-Buff analysis was performed on aqueous solutions of N-methylacetamide and acetamide using the Chemistry at HARvard Molecular Mechanics additive and Drude polarizable all-atom force fields. Comparison of a range of properties with experimental results, including Kirkwood-Buff integrals, excess coordination numbers, solution densities, partial molar values, molar enthalpy of mixing, showed both models to be well behaved at higher solute concentrations with the Drude model showing systematic improvement at lower solution concentrations. However, both models showed difficulties reproducing experimental activity derivatives and the excess Gibbs energy, with the Drude model performing slightly better. At the molecular level, the improved agreement of the Drude model at low solute concentrations is due to increased structure in the solute-solute and solute-solvent interactions. The present results indicate that the explicit inclusion of electronic polarization leads to improved modeling of dilute solutions even when those properties are not included as target data during force field optimization.

Crucial Importance of Water Structure Modification on TrimethylamineN-Oxide Counteracting Effect at High Pressure

Penetration of water molecules into the protein interior under high hydrostatic pressure conditions, leading to protein structural transition, is a well-known phenomenon. The counteracting effect of a naturally occurring osmolyte, trimethylamine N-oxide (TMAO), against pressure-induced protein denaturation is also well-established. But, what is largely unknown is the mechanism by which TMAO counteracts this protein denaturation. So to provide a molecular level understanding of how TMAO protects proteins at high pressure, we report here molecular dynamics (MD) computer simulation results for aqueous solutions of N-methylacetamide (NMA) with different TMAO concentrations over a wide range of pressures relevant to protein denaturation. Hydration behavior of NMA is analyzed at different conditions chosen. It is observed that hydrostatic pressure leads to a significant compression of hydration shell of nonpolar groups and increases hydration number. The compression is relatively insignificant in the vicinity of hydrogen bonding sites. TMAO can prevent pressure-induced enhanced hydration of NMA molecules. Interaction of TMAO with NMA and the structural and dynamical properties of water (site-site radial distribution function, coordination number, hydrogen-bond number, and lifetime) are also investigated to find the origin of the counteracting action of TMAO. Our results confirm that TMAO and pressure have counteracting effects on the water structural and dynamical properties, giving an explanation as to how TMAO counteracts pressure-conferred denaturation of proteins.

NMA Membership Application

We have performed the molecular dynamics simulations study to investigate the interaction of different force-field parameters of trimethylamine-N-oxide (TMAO) with aqueous solution of N-methylacetamide (NMA). We have calculated the number and energies of NMA-water, water-water and TMAO-water hydrogen bonds along with their hydrogen-bond lifetime, and structural relaxation times at varying concentrations of TMAO for three different force-fields. Our analysis indicates that compared to widely used Kast's model, other recently developed models strengthen the water-TMAO interaction. Since the TMAO force fields of Garcia and co-workers, and Netz and co-workers change the interaction behavior between the species in solution, it is expected that the observed translational, rotational and hydrogen bond properties will be changed accordingly. Our observations suggest that TMAO prefers to interact with NMA atomic sites through its methyl groups whereas hydrogen bonding interactions between oxygen atom of TMAO and amide-hydrogen of NMA (OTMAO…HNMA) also have a significant role which is more prominent in TMAO models of Garcia and Netz as compared to Kast's model. The hydrogen bond stability between oxygen of TMAO and hydrogen of water (OTMAO…HW) is overestimated by Netz and co-workers as compared with Kast and Garcia's models of TMAO.

Volumetric Properties of Amino Acids in Aqueous N-methylacetamide Solutions at 298.15 K

The apparent molar volumes (V φ ) of glycine, L-alanine and L-serine in aqueous 0 to 4 mol⋅kg−1 N-methylacetamide (NMA) solutions have been obtained by density measurement at 298.15 K. The standard partial molar volumes (\(V_{\phi}^{0})\) and standard partial molar volumes of transfer (\(\Delta_{\mathrm{tr}}V_{\phi}^{0})\) have been determined for these amino acids. It has been show that hydrophilic-hydrophilic interactions between the charged groups of the amino acids and the –CONH– group of NMA predominate for glycine and L-serine, but for L-alanine the interactions between its side group (–CH3) and NMA predominate. The –CH3 group of L-alanine has much more influence on the value of \(\Delta_{\mathrm{tr}}V_{\phi}^{0}\) than that of the –OH group of L-serine. The results have been interpreted in terms of a co-sphere overlap model.