Hydration of N-Hydroxyurea from Ab Initio Molecular Dynamics Simulations.

N-Hydroxyurea (HU) is an important chemotherapeutic agent used as a first-line treatment in conditions such as sickle cell disease and ß-thalassemia, among others. To date, its properties as a hydrated molecule in the blood plasma or cytoplasm are dramatically understudied, although they may be crucial to the binding of HU to the radical catalytic site of ribonucleotide reductase, its molecular target. The purpose of this work is the comprehensive exploration of HU hydration. The topic is studied using ab initio molecular dynamic (AIMD) simulations that apply a first principles representation of the electron density of the system. This allows for the calculation of infrared spectra, which may be decomposed spatially to better capture the spectral signatures of solute-solvent interactions. The studied molecule is found to be strongly hydrated and tightly bound to the first shell water molecules. The analysis of the distance-dependent spectra of HU shows that the E and Z conformers spectrally affect, on average, 3.4 and 2.5 of the closest H2O molecules, respectively, in spheres of radii of 3.7 Å and 3.5 Å, respectively. The distance-dependent spectra corresponding to these cutoff radii show increased absorbance in the red-shifted part of the water OH stretching vibration band, indicating local enhancement of the solvent's hydrogen bond network. The radially resolved IR spectra also demonstrate that HU effortlessly incorporates into the hydrogen bond network of water and has an enhancing effect on this network. Metadynamics simulations based on AIMD methodology provide a picture of the conformational equilibria of HU in solution. Contrary to previous investigations of an isolated HU molecule in the gas phase, the Z conformer of HU is found here to be more stable by 17.4 kJ·mol-1 than the E conformer, pointing at the crucial role that hydration plays in determining the conformational stability of solutes. The potential energy surface for the OH group rotation in HU indicates that there is no intramolecular hydrogen bond in Z-HU in water, in stark contrast to the isolated solute in the gas phase. Instead, the preferred orientation of the hydroxyl group is perpendicular to the molecular plane of the solute. In view of the known chaotropic effect of urea and its N-alkyl-substituted derivatives, N-hydroxyurea emerges as a unique urea derivative that exhibits a kosmotropic ordering of nearby water. This property may be of crucial importance for its binding to the catalytic site of ribonucleotide reductase with a concomitant displacement of a water molecule.

Weakly Hydrated Solute of Mixed Hydrophobic-Hydrophilic Nature.

Infrared (IR) spectroscopy is a commonly used and invaluable tool in studies of solvation phenomena in aqueous solutions. Concurrently, density functional theory calculations and ab initio molecular dynamics simulations deliver the solvation shell picture at the molecular detail level. The mentioned techniques allowed us to gain insights into the structure and energy of the hydrogen bonding network of water molecules around methylsulfonylmethane (MSM). In the hydration sphere of MSM, there are two types of populations of water molecules: a significant share of water molecules weakly bonded to the sulfone group and a smaller share of water molecules strongly bonded to each other around the methyl groups of MSM. The very weak hydrogen bond of water molecules with the hydrophilic group causes the extended network of water hydrogen bonds to be not "anchored" on the sulfone group, and consequently, the MSM hydration shell is labile.

Computational analysis of substituent effects on proton affinity and gas-phase basicity of TEMPO derivatives and their hydrogen bonding interactions with water molecules.

The study investigates the molecular structure of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and its derivatives in the gas phase using B3LYP and M06-2X functional methods. Intermolecular interactions are analyzed using natural bond orbital (NBO) and atoms in molecules (AIM) techniques. NO2-substituted TEMPO displays high reactivity, less stability, and softer properties. The study reveals that the stability of TEMPO derivatives is mainly influenced by LP(e) → σ∗ electronic delocalization effects, with the highest stabilization observed on the oxygen atom of the nitroxide moiety. This work also considers electron density, atomic charges, and energetic and thermodynamic properties of the studied NO radicals, and their relative stability. The proton affinity and gas-phase basicity of the studied compounds were computed at T = 298 K for O-protonation and N-protonation, respectively. The studied DFT method calculations show that O-protonation is more stable than N-protonation, with an energy difference of 16.64-20.77 kcal/mol (22.80-25.68 kcal/mol) at the B3LYP (M06-2X) method. The AIM analysis reveals that the N-O…H interaction in H2O complexes has the most favorable hydrogen bond energy computed at bond critical points (3, - 1), and the planar configurations of TEMPO derivatives exhibit the highest EHB values. This indicates stronger hydrogen bonding interactions between the N-O group and water molecules.

Protocol for developing a core outcome set for male infertility research: an international consensus development study.

STUDY QUESTION: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. WHAT IS KNOWN ALREADY: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. STUDY DESIGN SIZE DURATION: Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health's consensus development conference. PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTERESTS: This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586. TRIAL REGISTRATION DATE: N/A. DATE OF FIRST PATIENT'S ENROLMENT: N/A.

The influence of intermolecular correlations on the infrared spectrum of liquid dimethyl sulfoxide.

Dimethyl sulfoxide (DMSO) is routinely applied as an excellent, water-miscible solvent and chemical reagent. Some of the most important data concerning its liquid structure were obtained using infrared (IR) spectroscopy. However, the actual extent of intermolecular correlations that connect the isolated monomer spectrum to the IR response of the bulk liquid is poorly studied thus far. Using ab initio molecular dynamics (AIMD) simulations, IR spectra of liquid DMSO are obtained here from first principles and further analyzed using an array of sophisticated spectral decomposition techniques. The calculated spectra when unfolded in space reveal non-trivial spatial correlations underlying the IR response of liquid DMSO. It is unequivocally demonstrated that some of the fundamental vibrations visible in the intramolecular limit are effectively suppressed by the solvation environment due to symmetry reasons and thus disappear in the bulk limit, escaping experimental detection. Overall, DMSO as an aprotic solvent with dominant dipole-dipole interactions displays strong intermolecular correlations that contribute significantly to the IR spectra, on par with the situation observed in strongly associated liquids, such as water.

Hydration of Oxometallate Ions in Aqueous Solution.

The strength of hydrogen bonding to and structure of hydrated oxometallate ions in aqueous solution have been studied by double difference infrared (DDIR) spectroscopy and large-angle X-ray scattering (LAXS), respectively. Anions are hydrated by accepting hydrogen bonds from the hydrating water molecules. The oxygen atom of the permanganate and perrhenate ions form weaker and longer hydrogen bonds to water than the hydrogen bonds in bulk water (i.e., they act as structure breakers), while the oxygen atoms of the chromate, dichromate, molybdate, tungstate, and hydrogenvanadate ions form hydrogen bonds stronger than those in bulk water (i.e., they act as structure makers). The oxometallate ions form one hydration shell distinguishable from bulk water as determined by DDIR spectroscopy and LAXS. The hydration of oxoanions results in X-O bond distances ca. 0.02 Å longer than those in unsolvated ions in the solid state not involved in strong bonding to counterions. The oxygens of oxoanions with a central atom from the second and third series in the periodic table and the hydrogenvanadate ion hydrogen bind three hydrating water molecules, while oxygens of oxoanions with a heavier central atom only form hydrogen bonds to two water molecules.

Communication: Inside the water wheel: Intrinsic differences between hydrated tetraphenylphosphonium and tetraphenylborate ions.

Tetraphenylphosphonium tetraphenylborate (TPTB) is a common reference electrolyte in physical chemistry of solutions allowing for a convenient partitioning of thermodynamic properties into single-ion contributions. Here, we compute on the basis of ab initio molecular dynamics simulations the infrared (IR) spectra for hydrated constituent ions of the TPTB assumption. Using spectral decomposition techniques, we extract important information pertaining to the state of the hydration water from the IR spectra. Within their physical radii, the ions manage to capture about a dozen H2O molecules, several of which penetrate deep into the grooves between the tetrahedrally oriented "sails" of the rotating ions. In accordance with previous IR and Raman experiments, we find a considerable blue shift of the ν OH stretching band of liquid water by 240 cm-1 for TB, due to the extensive O-H⋯π hydrogen bonding, which is much weaker for TP. On the other hand, both ions show a second prominent band in the ν OH vibration range, only mildly blue shifted with respect to bulk water and attributable to the general distortion of the hydrogen bond network of the neighboring solvent. Finally, spatially resolved IR spectra allow us to pinpoint the exact location around the solutes, from which different IR resonances of the solvent originate.

Unusual Influence of Fluorinated Anions on the Stretching Vibrations of Liquid Water.

Infrared (IR) spectroscopy is a commonly used and invaluable tool in the studies of solvation phenomena in aqueous solutions. Concurrently, ab initio molecular dynamics (AIMD) simulations deliver the solvation shell picture at a molecular detail level and allow for a consistent decomposition of the theoretical IR spectrum into underlying spatial correlations. Here, we demonstrate how the novel spectral decomposition techniques can extract important information from the computed IR spectra of aqueous solutions of BF4- and PF6-, interesting weakly coordinating anions that have been known for a long time to alter the IR spectrum of water in an unusual manner. The distance-dependent spectra of both ions are analyzed using the spectral similarity method that provides a quantitative picture of both the spectrum of the solute-affected solvent and the number of solvent molecules thus altered. We find, in accordance with previous experiments, a considerable blue shift of the νOH stretching band of liquid water by 264 cm-1 for BF4- and 306 cm-1 for PF6-, with the affected numbers being 3.7 and 4.2, respectively. Considering also the additional information on solute-solvent dipolar couplings delivered by radially and spatially resolved IR spectra, the computational IR spectroscopy based on AIMD simulations is shown to be a viable predictive tool with strong interpretative power.

Visualizing spatially decomposed intermolecular correlations in the infrared spectra of aprotic liquids.

Infrared (IR) spectroscopy is commonly used to study intermolecular interactions in the liquid phase, including solvation phenomena. On the other hand, ab initio molecular dynamics (AIMD) simulations offer the possibility to obtain IR spectra from first principles. Surpassing the experiment, AIMD simulations can deliver additional information on the spatial intermolecular correlations underlying the IR spectrum of the liquid. Although such correlations contribute significantly to the IR spectra of associated liquids, such as water, they are equally important in the case of aprotic solvents, where dipole-dipole interactions are dominant. Here, the extent and non-trivial character of the spatial correlations in the IR spectra are demonstrated on the example of γ-butyrolactone (GBL), an important solvent in the rechargeable cell industry.

Unique agreement of experimental and computational infrared spectroscopy: a case study of lithium bromide solvation in an important electrochemical solvent.

Infrared (IR) spectroscopy is a widely used and invaluable tool in the studies of solvation phenomena in electrolyte solutions. Using state-of-the-art chemometric analysis of a spectral series measured in a concentration-dependent manner, the spectrum of the solute-affected solvent can be extracted, providing a detailed view of the structural and energetic states of the solvent molecules influenced by the solute. Concurrently, ab initio molecular dynamics (AIMD) simulations provide the solvation shell picture at an atomistic detail level and allow for a consistent decomposition of the theoretical IR spectrum in terms of distance-dependent contributions of the solvent molecules. Here, we show for the first time how the chemometric techniques designed with the analysis of experimental data in mind can be harnessed to extract corresponding information from the computed IR spectra for mutual benefit, but without any mutual input. The wide applicability of this two-track approach is demonstrated using lithium bromide solvation in γ-butyrolactone (GBL) as a showcase. GBL is a cyclic ester with extensive applications as a solvent in electrochemistry and we are particularly motivated by its usefulness in the rechargeable cell industry which justifies further studies of lithium cation solvation in GBL. The combination of experiment and simulations firmly asserts the strong solvent structuring character of Li+ and a comparatively weak influence exerted on the solvent by Br-.

Correlated Particle Motion and THz Spectral Response of Supercritical Water.

Molecular dynamics simulations of supercritical water reveal distinctly different distance-dependent modulations of dipolar response and correlations in particle motion compared to ambient conditions. The strongly perturbed H-bond network of water at supercritical conditions allows for considerable translational and rotational freedom of individual molecules. These changes give rise to substantially different infrared spectra and vibrational density of states at THz frequencies for densities above and below the Widom line that separates percolating liquidlike and clustered gaslike supercritical water.

Solvation shell resolved THz spectra of simple aqua ions - distinct distance- and frequency-dependent contributions of solvation shells.

Hydration of ions is a topic of broad relevance in chemistry and biology. Liquid-state terahertz spectroscopy has been demonstrated to be able to detect even small solute-induced changes in the hydrogen bond network dynamics at the solute-water interface. Here, we apply ab initio molecular dynamics simulations to study the solvation of Na(+) and Cl(-) in bulk water in the context of their far-infrared responses. Spatial decomposition schemes for infrared spectra down to the THz regime reveal the importance of both dipolar couplings and correlations in particle motion in these aqueous solutions. The explicit representation of the electronic structure properly captures the solute-solvent polarization effects that are crucial for the interpretation of recent experimental data. This demonstrates that theoretical spectroscopy significantly complements experimental measurements and provides most detailed insights by selectively monitoring the spectral activity due to distinct hydration spheres.

Molecular hydrogen solvated in water--A computational study.

The aqueous hydrogen molecule is studied with molecular dynamics simulations at ambient temperature and pressure conditions, using a newly developed flexible and polarizable H2 molecule model. The design and implementation of this model, compatible with an existing flexible and polarizable force field for water, is presented in detail. The structure of the hydration layer suggests that first-shell water molecules accommodate the H2 molecule without major structural distortions and two-dimensional, radial-angular distribution functions indicate that as opposed to strictly tangential, the orientation of these water molecules is such that the solute is solvated with one of the free electron pairs of H2O. The calculated self-diffusion coefficient of H2(aq) agrees very well with experimental results and the time dependence of mean square displacement suggests the presence of caging on a time scale corresponding to hydrogen bond network vibrations in liquid water. Orientational correlation function of H2 experiences an extremely short-scale decay, making the H2-H2O interaction potential essentially isotropic by virtue of rotational averaging. The inclusion of explicit polarizability in the model allows for the calculation of Raman spectra that agree very well with available experimental data on H2(aq) under differing pressure conditions, including accurate reproduction of the experimentally noted trends with solute pressure or concentration.

Spatial decomposition and assignment of infrared spectra of simple ions in water from mid-infrared to THz frequencies: Li(+)(aq) and F(-)(aq).

Ionic hydration is of fundamental relevance from chemical reactivity in aqueous solution to biomolecular function at physiological conditions. Vibrational spectroscopy belongs to the most widely used experimental methods in studies of solvation phenomena. There is, however, still limited molecular understanding as to how the vibrational response of solutions is modulated by the presence of solvation shells around solutes, i.e., by interfacial water. Liquid-state THz spectroscopy has been demonstrated to be able to detect even small solute-induced changes of the hydrogen bond dynamics at the solute-water interface. In many cases it reveals rather long-ranged dynamical correlations around solutes, involving many solvent molecules, that can be tackled theoretically by analyzing vibrational spectra in a distance-resolved manner. Here, several spatial decomposition schemes for infrared spectra are used to reveal the distinct distance- and frequency-dependent contributions of the solvation shells to the spectral response in aqueous solutions of Li(+) and F(-). The importance of an explicit representation of the solute's electronic structure for the proper description of solute-solvent polarization effects is demonstrated. The solvent's response to the presence of the solute is systematically disentangled and reveals important differences between the spectral responses due to intra- and intermolecular motion as probed in the mid- and far-infrared spectral windows, respectively.

Intramolecular interactions in crystals of tris(2,6-diisopropylphenoxy)silanethiol and its sodium salts.

Hydrolytically stable silanethiol tris(2,6-diisopropylphenoxy)silanethiol (TDST) has been synthesized and reacted with sodium metal. In solid state TDST exhibits π-interactions between the S-H unit and the π-system of the arene, replaced by cation-π interactions in its sodium salts. The interactions are documented by crystal structures and FT-IR spectroscopy.

Hydration of simple carboxylic acids from infrared spectra of HDO and theoretical calculations.

The hydration of carboxylic acids in dilute aqueous solutions is important for our understanding of their functioning in the biochemical context. Here we apply vibrational spectra of HDO isotopically diluted in H(2)O to study this phenomenon, using the difference spectra method for analysis and interpretation of the results. The spectra of HDO affected by formic, acetic, and propionic acid display characteristic component bands, significantly red-shifted from the bulk HDO band position. The appearance of these component bands is linked with isotopic substitution on the carboxylic acid molecule, which forms a short and strong hydrogen bond with a water molecule. Additionally, a charge separation due to the proton transfer in the neutral form of the complex leading to a contact ion pair formation may be inferred from the affected HDO spectra. Apart from the contraction of the principal acid-water hydrogen bond, it results in other major structural changes in the hydration shell, as revealed by density functional theory (DFT) calculations of optimal geometries of aqueous clusters of the studied acids.

Fourier transform infrared spectroscopic and theoretical study of water interactions with glycine and its N-methylated derivatives.

In this study we attempt to explain the molecular aspects of amino acids' hydration. Glycine and its N-methylated derivatives: N-methylglycine, N,N-dimethylglycine, and N,N,N-trimethylglycine were used as model solutes in aqueous solution, applying FT-IR spectroscopy as the experimental method. The quantitative version of the difference spectra method enabled us to obtain the solute-affected HDO spectra as probes of influenced water. The spectral results were confronted with density functional theory calculated structures of small hydration complexes of the solutes using the polarizable continuum model. It appears that the hydration of amino acids in the zwitterionic form can be understood allowing a synchronized fluctuation of hydrogen bonding between the solute and the water molecules. This effect is caused by a noncooperative interaction of water molecules with electrophilic groups of amino acid and by intramolecular hydrogen bond, allowing proton transfer from the carboxylic to the amine group, accomplishing by the chain of two to four water molecules. As a result, an instantaneous water-induced asymmetry of the carboxylate and the amino group of amino acid molecule is observed and recorded as HDO band splitting. Water molecules interacting with the carboxylate group give component bands at 2543 ± 11 and 2467 ± 15 cm(-1), whereas water molecules interacting with protons of the amine group give rise to the bands at 2611 ± 15 and 2413 ± 12 cm(-1). These hydration effects have not been recognized before and there are reasons to expect their validity for other amino acids.

Vibrational spectroscopic studies of N,N'-dimethylpropyleneurea-water system: affected solvent spectra and factor analysis.

FT-IR spectra of N,N'-dimethylpropyleneurea (DMPU)-water system have been measured in the 4000-500 cm(-1) range by Attenuated Total Reflectance (ATR) technique in the entire composition range. The hydration of DMPU in diluted aqueous solutions has been additionally studied with transmission FT-IR spectroscopy of isotopically diluted HDO in H(2)O, used as a probe of solute hydration. The spectra have been analysed with the quantitative version of the difference spectra method that leads to isolation of the spectrum of solvent affected by the presence of the solute. DMPU-affected HDO spectra provide information about the energetic state of water molecules in the hydration shell, while affected H(2)O spectra additionally reflect the structural state of the water hydrogen bond network. The CO stretching band of DMPU has been used to obtain also the H(2)O-affected DMPU spectrum. The affected H(2)O and DMPU spectra have been determined in infinite dilution approximation, as well as for increasing concentrations of the solute. These results are confronted with factor analysis of ATR spectra, which shows the presence of three well-defined intermolecular complexes in the studied system. Presumable structures of these complexes have been proposed on the basis of Density Functional Theory (DFT) calculations of optimal cluster geometries.

Systematic study of hydration patterns of phosphoric(V) acid and its mono-, di-, and tripotassium salts in aqueous solution.

Fourier transform infrared (FTIR) spectroscopy of the OD band of HDO molecules has been applied to perform a systematic study of various phosphate forms in the order of decreasing protonation: H3PO4, KH2PO4, K2HPO4, K3PO4. HDO isotopically diluted in H2O has been prepared by adding adequate amounts of D2O to aqueous solutions in ordinary water. The difference spectra procedure has been applied to remove the contribution of bulk water and thus to separate the spectra of solute-affected HDO. The position at maximum of the principal anion-affected HDO band for potassium phosphates moves in the order KH2PO4 (2478 cm(-1))>K2HPO4 (2363 cm(-1))>K3PO4 (2301 cm(-1)), that is, decreases with increasing solute basicity and charge. The number of moles of water affected by one mole of solute (N) equals 11.0, 13.8 and 16.2, respectively. Phosphoric acid affects statistically 13.9 water molecules and appears to be a "structure making" solute in water. The isotopic substitution with deuterium occurs also on the phosphate anions and phosphoric acid. The thus formed P-O-D groups interact with water molecules via strong hydrogen bonds and the relative strength of this interaction increases with increasing solute acidity. The plausible assignments of OD bands of HDO have been confirmed by calculating equilibrium structures of small aqueous clusters of the studied individual utilizing density functional theory. Further interpretation of the energetic and structural properties of hydrating water is enabled by calculating intermolecular interaction energy of water and probability distributions for interatomic oxygen-oxygen distance.

Hydration of carboxylate anions: infrared spectroscopy of aqueous solutions.

Hydration of carboxylate ions was studied in aqueous solutions of sodium salts by means of FTIR spectroscopy using the HDO molecule as a probe. The quantitative version of the difference spectra method has been applied to determine the solute-affected water spectra. They display two-component bands of affected HDO at ca. 2550 and 2420 cm(-1). These bands are attributed to the -COO(-) group of the R-COO(-) ion (R = H, CH(3), C(2)H(5)), because water molecules surrounding the substituent R behave roughly as molecules in the bulk phase. For the studied carboxylates the net water structure making effect is observed, which increases with electron-donor ability of R, by means of changing the relative intensity of solute-affected HDO component bands. The observed splitting of the carboxylate-ion-affected HDO band is unique for these anions. The experimental results were confronted with DFT-calculated structures of small gas-phase and polarizable continuum model (PCM) solvated aqueous clusters to establish the structural and energetic states of carboxylate ions hydrates. This was achieved by comparison of the calculated optimal geometries with the interatomic distances derived from HDO band positions. Different possibilities have been considered to explain the peculiar spectral results. The plausible explanation assumes symmetry breaking of the carboxylate ion induced by interaction with water solvent: C-O bond lengths of RCOO(-) and electric charge localization become unequal. It is demonstrated by nonequivalent interaction of oxygen atoms of the RCOO(-) anion with water molecules. Taking into account only the energetic effect, the phenomenon is explained by the anticooperative H-bond formation of the carboxylate group with water molecules, which increases with the electron-donor ability of the substituent R. In this interaction two water molecules play an important part, as appears from the calculated clusters. They interact with oxygen atoms of the RCOO(-) ion, forming a cooperative system, within which solvent molecules are nonequivalent with respect to H-bond formation with both proton-accepting sites of the solute. This additionally enhances solvent-induced symmetry breaking of carboxylate anion. Strongly hydrogen-bonded solvent is more effective in inducing symmetry breaking; thus, increasing the temperature decreases the splitting of the carboxylate-ion-affected water, as experimentally observed.