Charge Relay Without Proton Transfer: Coupling of Two Short Hydrogen Bonds via Imidazole in Models of Catalytic Triad of Serine Protease Active Site.

A homologous series of 20 substituted alcohol-imidazole-acetate model complexes imitating the charge relay system in Ser-His-Asp catalytic triad of serine proteases is considered quantum-chemically. We show qualitatively that the geometries of alcohol-imidazole and imidazole-acetate short hydrogen bonds are strongly coupled via the central imidazole and such complexes are capable of effectively relaying the charge from acetate to alcohol moiety upon relatively small concerted proton displacements. We hypothesize an alternative catalytic mechanism of serine proteases that does not require two complete proton transfers or hydrogen bond breakage between Ser and His residues.

Complexes of phosphine oxides with substituted phenols: hydrogen bond characterization based on shifts of PO stretching bands.

In this work IR spectral characteristics of PO groups are used to evaluate the strength of OHO hydrogen bonds. Three phosphine oxides: triphenylphosphine oxide, tributylphosphine oxide and hexamethylphosphoramide are investigated as proton acceptors. The results of the experimental IR study and DFT calculation of 30 complexes formed by phosphine oxides with various substituted phenols or CF3CH2OH in CCl4 solution at room temperature are reported. We show that the PO vibrational frequency changes non-linearly upon hydrogen bond formation and strengthening and that the shift of the PO band could be used for the estimation of hydrogen bond strength in complexes with phosphine oxides. The accuracy of these estimations and the influence of solvation effects on the main characteristics of complexes are discussed.

Evolution of vibrational bands upon gradual protonation/deprotonation of arsinic acid H2As(O)OH in media of different polarity.

This computational work is devoted to the investigation (MP2/def2-TZVP) of the geometry and IR parameters of arsinic acid H2AsOOH and its hydrogen-bonded complexes under vacuum and in media with different polarity. The medium effects were accounted for in two ways: (1) implicitly, using the IEFPCM model, varying the dielectric permittivity (ε) and (2) explicitly, by considering hydrogen-bonded complexes of H2As(O)OH with various hydrogen bond donors (41 complexes) or acceptors (38 complexes), imitating a gradual transition to the As(OH)2+ or AsO2- moiety, respectively. It was shown that the transition from vacuum to a medium with ε > 1 causes the As(O)OH fragment to lose its flatness. The solvent polar medium introduces significant changes in the geometry and IR spectral parameters of hydrogen-bonded complexes too: as the polarity of a medium increases, weak hydrogen bonds become weaker, and strong and medium hydrogen bonds become stronger; in the case of a complex with two hydrogen bonds cooperativity effects are observed. In almost all cases the driving force of these changes appears to be preferential solvation of charge-separated structures. In the limiting case of complete deprotonation (or conversely complete protonation) the vibrational frequencies of νAsO and νAs-O turn into νAs-O(asym) and νAs-O(sym), respectively. In the intermediate cases the distance between νAsO and νAs-O is sensitive to both implicit solvation and explicit solvation and the systematic changes of this distance can be used for estimation of the degree of proton transfer within the hydrogen bond.

Internal Vibrations of Pyridinium Cation in One-Dimensional Halide Perovskites and the Corresponding Halide Salts.

We investigate vibrations of the pyridinium cation PyH+ = C5H5NH+ in one-dimensional lead halide perovskites PyPbX3 and pyridinium halide salts PyHX (X- = I-, Br-), combining infrared absorption and Raman scattering methods at room temperature. Internal vibrations of the cation were assigned based on density functional theory modeling. Some of the vibrational bands are sensitive to perovskite or the salt environment in the solid state, while halide substitution has only a minor effect on them. These findings have been confirmed by 1H, 13C and 207Pb solid-state nuclear magnetic resonance (NMR) experiments. Narrower vibrational bands in perovskites indicate less disorder in these materials. The splitting of NH-group vibrational bands in perovskites can be rationalized the presence of nonequivalent crystal sites for cations or by more exotic phenomena such as quantum tunneling transition between two molecular orientations. We have shown how organic cations in hybrid organic-inorganic crystals could be used as spectators of the crystalline environment that affects their internal vibrations.

peri-Interactions in 1,8-bis(dimethylamino)naphthalene ortho-ketimine cations facilitate [1,5]-hydride shift: selective synthesis of 1,2,3,4-tetrahydrobenzo[h]quinazolines.

Selective heterocyclization leading to 1,2,3,4-tetrahydrobenzo[h]quinazolines from ortho-ketimines of 1,8-bis(dimethylamino)naphthalene (DmanIms) under acid catalysis has been revealed. In contrast to the rather unreactive N,N-dimethylaniline ortho-ketimine, DmanIms readily undergo this transformation without an additional catalyst. This distinction in the reactivity underscores the importance of the second peri-NMe2 group in DmanIms, which facilitates a [1,5]-hydride shift and the subsequent cyclization. The cascade of peri-interactions emerging between 1-NMe2 and 8-NMe2 groups has been identified as a reason for the catalytic effect: (1) the hydrogen bond in the DmanIm dication constrains 1-NMe2 in the desired position providing proximity of reaction centers, (2) the repulsion of the lone pairs of 8-NMe2 group and unrelaxed 1-NMe2 group arising right after deprotonation process reduces the Gibbs free energy of activation (ΔG‡) for the straight hydride shift, and (3) the electrostatic interaction between 8-NMe2 and the charged NCH2+ group in the intermediate increases the ΔG‡ for the reverse hydride shift.

Phosphine oxides as NMR and IR spectroscopic probes for the estimation of the geometry and energy of PO⋯H-A hydrogen bonds.

In this work we evaluate the possibility of using the NMR and IR spectral properties of the PO group to estimate the geometry and strength of hydrogen bonds which it forms with OH-, NH- and CH-acids. The results of the DFT study of 70 hydrogen-bonded 1 : 1 complexes of a model trimethylphosphine oxide, Me3PO, with various proton donors in the gas phase and in aprotic medium (modelled as a polarizable continuum) are presented. Four types of hydrogen bonds with the general formula Me3PO⋯H-A were considered, where the A atom is O, C, and N (neutral or cationic acids). Within the selected set of complexes the hydrogen bond energy varies over a wide range (ca. 0-85 kJ mol-1). We show that it is possible to use simple correlations to estimate the energy and geometry of OHO, NHO and CHO hydrogen bonds from the changes of isotropic 31P NMR chemical shifts and harmonic PO stretching vibration frequencies upon complexation. Such correlations also could be used to estimate the proton-donating ability (and Brønsted acidity; pKa) of OH acids.

Self-association of diphenylpnictoginic acids in solution and solid state: covalent vs. hydrogen bonding.

Triphenylpnictogens were oxidized to access diphenylpnictioginic acids Ph2XOOH (X = P, As, Sb, Bi). It was shown that oxidation with chloramine-T does not lead to the cleavage of a C-pnictogen bond. The preliminary reductive cleavage with sodium in liquid ammonia followed by the oxidation with hydrogen peroxide was successfully utilised for the synthesis of diphenylphosphinic and diphenylarsinic acids. It was shown that in solid state (by means of XRD), all diphenylpnictoginic acids form polymeric chains. Diphenylbismuthinic and diphenylantimonic acids form polymeric covalent adducts, while diphenylphosphinic and diphenylarsinic chains are associated through hydrogen bonding. Unlike diphenylphosphinic acid, diphenilarsinic acid forms two polymorphs of hydrogen-bonded infinite chains. In solution in a polar aprotic solvent diphenylarsinic acid, similarly to dimethylarsinic, forms hydrogen-bonded cyclic dimers together with a small amount of cyclic trimers.

Simultaneous Estimation of Two Coupled Hydrogen Bond Geometries from Pairs of Entangled NMR Parameters: The Test Case of 4-Hydroxypyridine Anion.

The computational method for estimating the geometry of two coupled hydrogen bonds with geometries close to linear using a pair of spectral NMR parameters was proposed. The method was developed based on the quantum-chemical investigation of 61 complexes with two hydrogen bonds formed by oxygen and nitrogen atoms of the 4-hydroxypyridine anion with OH groups of substituted methanols. The main idea of the method is as follows: from the NMR chemical shifts of nuclei of atoms forming the 4-hydroxylpyridine anion, we select such pairs, whose values can be used for simultaneous determination of the geometry of two hydrogen bonds, despite the fact that every NMR parameter is sensitive to the geometry of each of the hydrogen bonds. For these parameters, two-dimensional maps of dependencies of NMR chemical shifts on interatomic distances in two hydrogen bonds were constructed. It is shown that, in addition to chemical shifts of the nitrogen atom and quaternary carbon, which are experimentally difficult to obtain, chemical shifts of the carbons and protons of the CH groups can be used. The performance of the proposed method was evaluated computationally as well on three additional complexes with substituted alcohols. It was found that, for all considered cases, hydrogen bond geometries estimated using two-dimensional correlations differed from those directly calculated by quantum-chemical methods by not more than 0.04 Å.

The Distance between Minima of Electron Density and Electrostatic Potential as a Measure of Halogen Bond Strength.

In this study, we present results of a detailed topological analysis of electron density (ED) of 145 halogen-bonded complexes formed by various fluorine-, chlorine-, bromine-, and iodine-containing compounds with trimethylphosphine oxide, Me3PO. To characterize the halogen bond (XB) strength, we used the complexation enthalpy, the interatomic distance between oxygen and halogen, as well as the typical set of electron density properties at the bond critical points calculated at B3LYP/jorge-ATZP level of theory. We show for the first time that it is possible to predict the XB strength based on the distance between the minima of ED and molecular electrostatic potential (ESP) along the XB path. The gap between ED and ESP minima exponentially depends on local electronic kinetic energy density at the bond critical point and tends to be a common limiting value for the strongest halogen bond.

Hydration of selenolate moiety: Ab initio investigation of properties of O-H⋯Se(-) hydrogen bonds in CH3 Se(-)⋯(H2 O)n clusters.

This work is devoted to investigations of the influence of O-H···Se(-) hydrogen bonds on the electronic shells of selenolate R-Se(-) fragment (R═CH3 ). The geometric, energetic and nuclear magnetic resonance (NMR) spectral parameters for various conformers of CH3 Se(-)⋯(H2 O)n clusters with n = 0-6 were calculated at CCSD/aug-cc-pVDZ level of theory. For selenolate anion CH3 Se(-) solvation free energy was calculated, and for water media it is equal to -71.41 kcal/mol. For O-H···Se(-) hydrogen bonds the proportionality coefficients between QTAIM parameters at (3; -1) bond critical point and the strength of an individual hydrogen bond ∆E were proposed. It was shown, that despite a relative weakness of O-H···Se(-) hydrogen bonds, the outer electronic shell of the selenium atom changes significantly upon formation of each hydrogen bond. This, in turn, cause the dramatic change of NMR parameters of selenium nuclei.

Noncovalent Axial I⋠⋠⋠Pt⋠⋠⋠I Interactions in Platinum(II) Complexes Strengthen in the Excited State.

Coordination compounds of platinum(II) participate in various noncovalent axial interactions involving metal center. Weakly bound axial ligands can be electrophilic or nucleophilic; however, interactions with nucleophiles are compromised by electron density clashing. Consequently, simultaneous axial interaction of platinum(II) with two nucleophilic ligands is almost unprecedented. Herein, we report structural and computational study of a platinum(II) complex possessing such intramolecular noncovalent I⋅⋅⋅Pt⋅⋅⋅I interactions. Structural analysis indicates that the two iodine atoms approach the platinum(II) center in a "side-on" fashion and act as nucleophilic ligands. According to computational studies, the interactions are dispersive, weak and anti-cooperative in the ground electronic state, but strengthen substantially and become partially covalent and cooperative in the lowest excited state. Strengthening of I⋅⋅⋅Pt⋅⋅⋅I contacts in the excited state is also predicted for the sole previously reported complex with analogous axial interactions.

On the influence of water molecules on the outer electronic shells of R-SeH, R-Se(-) and R-SeOH fragments in the selenocysteine amino acid residue.

In this computational work (MP2/aug-cc-pVTZ) we investigated the features of the outer electronic shells of R-SeH, R-Se(-) and R-SeOH fragments (R = CH3), which can be considered as simplified models for the forms of the active centres of glutathione peroxidases GPx along their catalytic pathway (reduction of peroxides). It is shown that the preferential direction of a nucleophilic attack on the R-Se(-) fragment by a peroxide molecule is determined by the presence of the electron-depleted region of the selenium atom in front of the C-Se bond and nucleophilic attack can be facilitated by the solvation of R-Se(-) by water molecules. Such solvation does not block the direction of potential nucleophilic attack and also leads to the increase of the maximal value of the molecular electrostatic potential on the selenium atom. It was shown that the 77Se NMR chemical shift is sensitive both to the oxidation state and the hydration state of the selenium-containing fragment.

Sensitivity of 31 P NMR chemical shifts to hydrogen bond geometry and molecular conformation for complexes of phosphinic acids with pyridines.

The results of the quantum-chemical investigation of a series of hydrogen-bonded 1:1 acid-base complexes formed by model phosphinic acids, Me2 POOH, and PhHPOOH, are reported. A series of substituted pyridines (pKa range from 0.5 to 10) was chosen as proton acceptors. Gradual changes of isotropic 31 P nuclear magnetic resonance (NMR) chemical shift, δP, were correlated with the bridging proton position in the intermolecular OHN hydrogen bond, namely, r (OH) distance; the proposed correlation could easily be extended to other phosphinic acids as well. For complexes with pyridine and 2,4,6-trimethylpyridine, we have investigated in more detail several factors influencing the δP values: (1) the proton transfer within the OHN hydrogen bond; (2) the rotation of the pyridine ring around the hydrogen bond axis (associated with the formation/breakage of additional weak PO···H-C hydrogen bond); and (3) the rotation of the phenyl substituent in phenylphosphinic acid around the P-C axis. All these factors appeared to be of similar magnitude, thus masking their individual contributions that have to be independently estimated for a reliable spectral interpretation.

Polymorphism and Conformational Equilibrium of Nitro-Acetophenone in Solid State and under Matrix Conditions.

Conformational and polymorphic states in the nitro-derivative of o-hydroxy acetophenone have been studied by experimental and theoretical methods. The potential energy curves for the rotation of the nitro group and isomerization of the hydroxyl group have been calculated by density functional theory (DFT) to estimate the barriers of the conformational changes. Two polymorphic forms of the studied compound were obtained by the slow and fast evaporation of polar and non-polar solutions, respectively. Both of the polymorphs were investigated by Infrared-Red (IR) and Raman spectroscopy, Incoherent Inelastic Neutron Scattering (IINS), X-ray diffraction, nuclear quadrupole resonance spectroscopy (NQR), differential scanning calorimetry (DSC) and density functional theory (DFT) methods. In one of the polymorphs, the existence of a phase transition was shown. The position of the nitro group and its impact on the crystal cell of the studied compound were analyzed. The conformational equilibrium determined by the reorientation of the hydroxyl group was observed under argon matrix isolation. An analysis of vibrational spectra was achieved for the interpretation of conformational equilibrium. The infrared spectra were measured in a wide temperature range to reveal the spectral bands that were the most sensitive to the phase transition and conformational equilibrium. The results showed the interrelations between intramolecular processes and macroscopic phenomena in the studied compound.

Spectroscopic Identification of Hydrogen Bond Vibrations and Quasi-Isostructural Polymorphism in N-Salicylideneaniline.

The ortho-hydroxy aryl Schiff base 2-[(E)-(phenylimino)methyl]phenol and its deutero-derivative have been studied by the inelastic incoherent neutron scattering (IINS), infrared (IR) and Raman experimental methods, as well as by Density Functional Theory (DFT) and Density-Functional Perturbation Theory (DFPT) simulations. The assignments of vibrational modes within the 3500-50 cm-1 spectral region made it possible to state that the strong hydrogen bond in the studied compound can be classified as the so-called quasi-aromatic bond. The isotopic substitution supplemented by the results of DFT calculations allowed us to identify vibrational bands associated with all five major hydrogen bond vibrations. Quasi-isostructural polymorphism of 2-[(E)-(phenylimino)methyl]phenol (SA) and 2-[(E)-(phenyl-D5-imino)methyl]phenol (SA-C6D5) has been studied by powder X-ray diffraction in the 20-320 K temperature range.

Lone pairs mapping by Laplacian of 3 He NMR chemical shift.

Results of approbation of a new quantum mechanical approach of lone pairs (LPs) visualization, its optimization and testing on a range of model molecules are presented. The main idea of proposed methodology is using 3 He atom as a probe for investigating electronic shells of species with LPs. As model objects, we consider "classical" examples of hydrogen cyanide, methanimine, ammonia, phosphine, formaldehyde, water, and hydrogen sulfide. It is shown that LPs can be visualized by means of 3D maps of Laplacian of 3 He chemical shift ∇2 δHe . NMR calculations could be performed using level of theory as low as B3LYP/6-31G, allowing for the reduction of computational time without significant loss of quality. Advantages of our approach are discussed in comparison with usual methods of lone pairs visualization (electron localization function, molecular electrostatic potential).

How Strong is Hydrogen Bonding to Amide Nitrogen?

The protonation of the carboxamide nitrogen atom is an essential part of in vivo and in vitro processes (cis-trans isomerization, amides hydrolysis etc). This phenomenon is well studied in geometrically strongly distorted amides, although there is little data concerning the protonation of undistorted amides. In the latter case, the participation of amide nitrogen in hydrogen bonding (which can be regarded as the incipient state of a proton transfer process) is less well-studied. Thus, it would be a worthy goal to investigate the enthalpy of this interaction. We prepared and investigated a set of peri-substituted naphthalenes containing the protonated dimethylamino group next to the amide nitrogen atom ("amide proton sponges"), which could serve as models for the study of an intramolecular hydrogen bond with the amide nitrogen atom. X-Ray analysis, NMR spectra, basicity values as well as quantum chemical calculations revealed the existence of a hydrogen bond with the amide nitrogen, that should be attributed to the borderline between moderate and weak intramolecular hydrogen bonds (2-7 kcal ⋅ mol-1 ).

Unusual behaviour of the spin-spin coupling constant 1JCH upon formation of CHX hydrogen bond.

One-bond coupling constants 1JXY are usually used as a measure of the corresponding XY interatomic distances. However, the physical nature of this correlation is not well understood and, in some cases, a counterintuitive behaviour of 1JXY upon hydrogen bonded complex formation has been reported. In this work, the behavior of 1JCH upon formation and strengthening of complexes with CHX hydrogen bonds and upon a proton transfer process is investigated by means of 1H NMR spectroscopy and quantum chemical calculations. 1H NMR spectra of 1,1-dinitroethane solution at room temperature in various solvents (carbon tetrachloride, chloroform, dichloromethane, acetone, dimethylformamide and dimethyl sulfoxide) illustrate the increase of 1JCH by several Hz upon an increase of the complex strength. Computational results (MP2/aug-cc-pVDZ) reproduce this observation and allow one to conclude that the increase of 1JCH is mainly caused by the change of the carbon hybridization (an increase of s-character), rather than by the change in interatomic distance rCH. The behavior of 1JCH was also examined computationally for a wide range of CHX hydrogen bond energies and geometries. For this purpose, quantum-chemical modeling of the partial proton transfer process for complexes formed by 1,1-dinitroethane and trinitromethane as hydrogen bond donors with acetone, pyridine and fluoride anion as hydrogen bond acceptors was performed. The obtained results have confirmed the above-mentioned idea - for rather weak complexes, the dominant impact on the change of 1JCH magnitude is the increase of the s-character of carbon atom hybridization, while for complexes with a significantly transferred proton, the exponential decrease of the Fermi-contact term dominates.

H/D Isotope Effects on 1H-NMR Chemical Shifts in Cyclic Heterodimers and Heterotrimers of Phosphinic and Phosphoric Acids.

Hydrogen-bonded heterocomplexes formed by POOH-containing acids (diphenylphosphoric 1, dimethylphosphoric 2, diphenylphosphinic 3, and dimethylphosphinic 4) are studied by the low-temperature (100 K) 1H-NMR and 31P-NMR using liquefied gases CDF3/CDF2Cl as a solvent. Formation of cyclic dimers and cyclic trimers consisting of molecules of two different acids is confirmed by the analysis of vicinal H/D isotope effects (changes in the bridging proton chemical shift, δH, after the deuteration of a neighboring H-bond). Acids 1 and 4 (or 1 and 3) form heterotrimers with very strong (short) H-bonds (δH ca. 17 ppm). While in the case of all heterotrimers the H-bonds are cyclically arranged head-to-tail, ···O=P-O-H···O=P-O-H···, and thus their cooperative coupling is expected, the signs of vicinal H/D isotope effects indicate an effective anticooperativity, presumably due to steric factors: when one of the H-bonds is elongated upon deuteration, the structure of the heterotrimer adjusts by shortening the neighboring hydrogen bonds. We also demonstrate the formation of cyclic tetramers: in the case of acids 1 and 4 the structure has alternating molecules of 1 and 4 in the cycle, while in case of acids 1 and 3 the cycle has two molecules of 1 followed by two molecules of 3.

Phosphine Oxides as Spectroscopic Halogen Bond Descriptors: IR and NMR Correlations with Interatomic Distances and Complexation Energy.

An extensive series of 128 halogen-bonded complexes formed by trimethylphosphine oxide and various F-, Cl-, Br-, I- and At-containing molecules, ranging in energy from 0 to 124 kJ/mol, is studied by DFT calculations in vacuum. The results reveal correlations between R-X⋅⋅⋅O=PMe3 halogen bond energy ΔE, X⋅⋅⋅O distance r, halogen's σ-hole size, QTAIM parameters at halogen bond critical point and changes of spectroscopic parameters of phosphine oxide upon complexation, such as 31P NMR chemical shift, ΔδP, and P=O stretching frequency, Δν. Some of the correlations are halogen-specific, i.e., different for F, Cl, Br, I and At, such as ΔE(r), while others are general, i.e., fulfilled for the whole set of complexes at once, such as ΔE(ΔδP). The proposed correlations could be used to estimate the halogen bond properties in disordered media (liquids, solutions, polymers, glasses) from the corresponding NMR and IR spectra.