Dynamic and relativistic effects on Pt-Pt indirect spin-spin coupling in aqueous solution studied by ab initio molecular dynamics and two- vs four-component density functional NMR calculations.

Treating 195Pt nuclear magnetic resonance parameters in solution remains a considerable challenge from a quantum chemistry point of view, requiring a high level of theory that simultaneously takes into account the relativistic effects, the dynamic treatment of the solvent-solute system, and the dynamic electron correlation. A combination of Car-Parrinello molecular dynamics (CPMD) and relativistic calculations based on two-component zeroth order regular approximation spin-orbit Kohn-Sham (2c-ZKS) and four-component Dirac-Kohn-Sham (4c-DKS) Hamiltonians is performed to address the solvent effect (water) on the conformational changes and JPtPt1 coupling. A series of bridged PtIII dinuclear complexes [L1-Pt2(NH3)4(Am)2-L2]n+ (Am = α-pyrrolidonate and pivalamidate; L = H2O, Cl-, and Br-) are studied. The computed Pt-Pt coupling is strongly dependent on the conformational dynamics of the complexes, which, in turn, is correlated with the trans influence among axial ligands and with the angle N-C-O from the bridging ligands. The J-coupling is decomposed in terms of dynamic contributions. The decomposition reveals that the vibrational and explicit solvation contributions reduce JPtPt1 of diaquo complexes (L1 = L2 = H2O) in comparison to the static gas-phase magnitude, whereas the implicit solvation and bulk contributions correspond to an increase in JPtPt1 in dihalo (L1 = L2 = X-) and aquahalo (L1 = H2O; L2 = X-) complexes. Relativistic treatment combined with CPMD shows that the 2c-ZKS Hamiltonian performs as well as 4c-DKS for the JPtPt1 coupling.

Molecular dynamics and NMR reveal the coexistence of H-bond-assisted and through-space JFH coupling in fluorinated amino alcohols.

The JFH coupling constants in fluorinated amino alcohols were investigated through experimental and theoretical approaches. The experimental JFH couplings were only reproduced theoretically when explicit solvation through molecular dynamics (MD) simulations was conducted in DMSO as the solvent. The combination of MD conformation sampling and DFT NMR spin-spin coupling calculations for these compounds reveals the simultaneous presence of through-space (TS) and hydrogen bond (H-bond) assisted JFH coupling between fluorine and hydrogen of the NH group. Furthermore, MD simulations indicate that the hydrogen in the amino group participates in both an intermolecular bifurcated H-bond with DMSO and in transmitting the observed JFH coupling. The contribution of TS to the JFH coupling is due to the spatial proximity of the fluorine and the NH group, aided by a combination of the non-bonding transmission pathway and the hydrogen bonding pathway. The experimental JFH coupling observed for the molecules studied should be represented as 4TS/1hJFH coupling.

Solvation effects on glyphosate protonation and deprotonation states evaluated by mass spectrometry and explicit solvation simulations.

Glyphosate is a widely used herbicide, and its protonation and deprotonation sites are fundamental to understanding its properties. In this work, the sodiated, protonated, and deprotonated glyphosate were evaluated in the gas phase by infrared multiple photon dissociation spectroscopy to determine the exact nature of these coordination, protonation, and deprotonation states in the gas phase. In this context, Natural Bond Orbital analyses were carried out to unravel interactions that govern glyphosate (de)protonation states in the gas phase. The solvent effect on the protonation/deprotonation equilibria was also investigated by implicit (Solvation Model Based on Density and polarizable continuum models) and explicit solvation models (Monte Carlo and Molecular Dynamics simulations). These results show that glyphosate is protonated in the phosphonate group in the gas phase because of the strong hydrogen bond between the carboxylic oxygen (O7) and the protonated phosphonate group (O8-H19), while the most stable species in water is protonated at the amino group because of the preferential interaction of the NH2 + group and the solvent water molecules. Similarly, deprotonated glyphosate [Glyp-H]- was shown to be deprotonated at the phosphonate group in the gas phase but not in solution, also because of the preferential solvation of the NH2 + group present in the other deprotomers. Therefore, these results show that the stabilization of the protonated amino group by the solvent molecules is the governing factor of the (de)protonation equilibrium of glyphosate in water.

p-Aminobenzoic acid protonation dynamics in an evaporating droplet by ab initio molecular dynamics.

Protonation equilibria are known to vary from the bulk to microdroplet conditions, which could induce many chemical and physical phenomena. Protonated p-aminobenzoic acid (PABA + H+) can be considered a model for probing the protonation dynamics in an evaporating droplet, as its protonation equilibrium is highly dependent on the formation conditions from solution via atmospheric pressure ionization sources. Experiments using diverse experimental techniques have shown that protic solvents allow formation of the O-protomer (PABA protonated in the carboxylic acid group) stable in the gas phase, while aprotic solvents yield the N-protomer (protonated in the amino group) that is the most stable protomer in solution. In this work, we explore the protonation equilibrium of PABA solvated by different numbers of water molecules (n = 0 to 32) using ab initio molecular dynamics. For n = 8-32, the protonation is either at the NH2 group or in the solvent network. The solvent network interacts with the carboxylic acid group, but there is no complete proton transfer to form the O-protomer. For smaller clusters, however, solvent-mediated proton transfers to the carboxylic acid were observed, both via the Grotthuss mechanism and the vehicle or shuttle mechanism (for n = 1 and 2). Thermodynamic considerations allowed a description of the origins of the kinetic trapping effect, which explains the observation of the solution structure in the gas phase. This effect likely occurs in the final evaporation steps, which are outside the droplet size range covered by previous classical molecular dynamics simulations of charged droplets. These results may be considered relevant in determining the nature of the species observed in the ubiquitous ESI based mass spectrometry analysis, and in general for droplet chemistry, explaining how protonation equilibria are drastically changed from bulk to microdroplet conditions.

Solvent effect on the 195Pt NMR properties in pyridonate-bridged PtIII dinuclear complex derivatives investigated by ab initio molecular dynamics and localized orbital analysis.

An ab initio molecular dynamics investigation of the solvent effect (water) on the structural parameters, 195Pt NMR spin-spin coupling constants (SSCCs) and chemical shifts of a series of pyridonate-bridged PtIII dinuclear complexes is performed using Kohn-Sham (KS) Car-Parrinello molecular dynamics (CPMD) and relativistic hybrid KS NMR calculations. The indirect solvent effect (via structural changes) has a dramatic effect on the 1JPtPt SSCCs. The complexes exhibit a strong trans influence in solution, where the Pt-Pt bond lengthens with increasing axial ligand σ-donor strength. In the diaqua complex, where the solvent effect is more pronounced, the SSCCs averaged for CPMD configurations with explicit plus implicit solvation agree much better with the experimental data, while the calculations for static geometry and CPMD unsolvated configurations show large deviations with respect to experiment. The combination of CPMD with hybrid KS NMR calculations provides a much more realistic computational model that reproduces the large magnitudes of 1JPtPt and 195Pt chemical shifts. An analysis of 1JPtPt in terms of localized and canonical orbitals shows that the SSCCs are driven by changes in the s-character of the natural atomic orbitals of Pt atoms, which affect the 'Fermi contact' mechanism.

Dealing with Hydrogen Bonding on the Conformational Preference of 1,3-Aminopropanols: Experimental and Molecular Dynamics Approaches.

This study expands the knowledge on the conformational preference of 1,3-amino alcohols in the gas phase and in solution. By employing Fourier transform infrared spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, density functional theory (DFT) calculations, quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO) analysis, and molecular dynamics (MD), the compounds 3-aminopropan-1-ol (1), 3-methylaminopropan-1-ol (2), and 3-dimethylaminopropan-1-ol (3) are evaluated. The results show that the most stable conformation of each compound in the gas phase and in nonpolar solvents exhibited an O-H···N intramolecular hydrogen bond (IHB). Based on the experimental and theoretical OH-stretching frequencies, the IHB becomes stronger from 1 to 3. In addition, from the experimental NMR J-couplings, the IHB conformers are predominant in nonbasic solvents, representing 70-80% of the conformational equilibrium, while in basic solvents, such conformers only represent 10%. DFT calculations and QTAIM analysis in the gas phase support the occurrence of IHBs in these compounds. The MD simulation indicates that the non-hydrogen-bonded conformers are the lowest energy conformations in the solution because of molecular interactions with the solvent, while they are absent in the implicit solvation model based on density. NBO analysis suggests that methyl groups attached on the nitrogen atom affect the charge transfer energy involved in the IHB. This effect occurs mostly because of a decrease in the s-character of the LPN orbital along with weakening of the charge transfer from LPN to σ*OH, which is caused by an increase in the C-C-N bond angle.

The halogen effect on the 13C NMR chemical shift in substituted benzenes.

Recent research [Chem. Sci., 2017, 8, 6570-6576] showed for R-substituted benzenes with R = NH2, NO2 that the substitution effects on the 13C NMR chemical shifts are correlated with changes in the σ-bonding framework and do not follow directly the electron-donating or -withdrawing effects on the π orbitals. In the present work we extend the study to halogen (X = F, Cl, Br or I) substituted R-benzenes. The effect of X and R groups on 13C NMR chemical shifts in X-R-benzenes are investigated by density functional calculations and localized molecular orbital analyses. Deshielding effects caused by the X atom on the directly bonded carbon nucleus are observed for F and Cl derivatives due to a paramagnetic coupling between occupied π orbitals and unoccupied antibonding orbitals. The SO coupling plays an important role in the carbon magnetic shielding of Br and I derivatives, as is well known, and the nature of X also modulates the 13C paramagnetic shielding contributions. Overall, the X and R substituent effects are approximately additive.

NMR J-Coupling Constants of Tl-Pt Bonded Metal Complexes in Aqueous Solution: Ab Initio Molecular Dynamics and Localized Orbital Analysis.

The influence of solvent (water) coordination and dynamics on the electronic structure and nuclear magnetic resonance (NMR) indirect spin-spin coupling (J-coupling) constants in a series of Tl-Pt bonded complexes is investigated using Kohn-Sham (KS) Car-Parrinello molecular dynamics (CPMD) and relativistic hybrid KS NMR calculations with and without coordination to water. Coordination of the Tl center by water molecules has a dramatic impact on 1J(Tl-Pt) and other J-coupling constants. It is shown that a previous computational study of the same complexes using static optimized structures and nonhybrid functionals was correct about the important role of the solvent but obtained reasonable agreement with experimental NMR data because of a cancellation of substantial errors. For example, the CPMD trajectories show that on average the inner coordination shell of Tl is not saturated, as previously assumed, which leads to poor agreement with experiment when the J-coupling constants are averaged over the CPMD trajectories using NMR calculations with nonhybrid functionals. The combination of CPMD with hybrid KS NMR calculations provides a much more realistic computational model that reproduces the large magnitudes of 1J(Tl-Pt) and the correct trends for other coupling constants. An analysis of 1J(Tl-Pt) in terms of localized orbitals shows that the presence of coordinating water molecules increases the capacity for covalent interactions between Tl and Pt. There is pronounced multicenter bonding along the metal-metal axis of the complexes.

NMR spin-spin coupling constants: bond angle dependence of the sign and magnitude of the vicinal (3)JHF coupling.

The dependence of the magnitude and sign of (3)JHFF on the bond angle in fluoro-cycloalkene compounds is evaluated by electronic structure calculations using different levels of theory, viz. DFT, SOPPA(CCSD) and SOPPA(CC2). Localized molecular orbital contributions to (3)JHFF are analyzed to assess which orbitals are responsible for (3)JHFF and which are the most important coupling transmission mechanisms for each compound. Fluoro-ethylene is used as a model system to evaluate the dependence of the (3)JHFF coupling constant on the angle between the σCα-F and σCα'-HF vectors. Through-space and hyperconjugative transmission pathways and ring strain are identified as responsible for the opposite trend between (3)JHFF and bond angle, and for the negative signs obtained for the two molecules, respectively. One of the fluorine lone pairs, σCα'-HF, σCα-F, σCα'-Cß' bonding orbitals and the σ*Cα-F antibonding orbital are involved in the J-coupling pathways, according to analyses of pairwise-steric and hyperconjugative energies.

Formation of isomers of anionic hemiesters of sugars and carbonic acid in aqueous medium.

Hemiesters of carbonic acid can be freely formed in aqueous media containing HCO3(-)/CO2 and mono- or poly-hydroxy compounds. Herein, (13)C NMR spectroscopy was used to identify isomers formed in aqueous solutions of glycerol (a prototype compound) and seven carbohydrates, as well as to estimate the equilibrium constant of formation (Keq). Although both isomers are formed, glycerol 1-carbonate corresponds to 90% of the product. While fructose and ribose form an indistinct mixture of isomers, the anomers of d-glucopyranose 6-carbonate correspond to 74% of the eight isomers of glucose carbonate that were detected. The values of Keq for the disaccharides sucrose (4.3) and maltose (4.2) are about twice the values for the monosaccharides glucose (2.0) and fructose (2.3). Ribose (Keq = 0.89)-the only sugar without a significant concentration of a species containing a -CH2OH group in an aqueous solution-resulted in the smallest Keq. On the basis of the Keq value and the concentrations of HCO3(-) and glucose in blood, one can anticipate a concentration of 2-4 µmol L(-1) for glucose 6-carbonate, which corresponds to ca. of 10% of its phosphate counterpart (glucose 6-phosphate).

Effects of stereoelectronic interactions on the relativistic spin-orbit and paramagnetic components of the (13)C NMR shielding tensors of dihaloethenes.

In this study, stereoelectronic interactions were considered to explain the experimental difference in the magnitude of the known heavy-atom effect on the (13)C NMR chemical shifts in cis- and trans-1,2-dihaloethene isomers (halo = F, Cl, Br or I). The experimental values were compared to the calculated values with various DFT functionals using both the nonrelativistic approach (NR) and the relativistic approximations SR-ZORA (SR) and SO-ZORA (SO). NBO and NLMO contributions to the (13)C NMR shielding tensors were determined to assess which stereoelectronic interactions have a more important effect on the shielding tensor in each principal axis system (PAS) coordinate. These analyses associated with the orbital rotation model and the HOMO-LUMO energy gap enable rationalization of trends between cis and trans isomers from fluorine to iodine derivatives. Both paramagnetic and SO shielding terms were responsible for the observed trends. It was possible to conclude that the steric interactions between the two iodine atoms and the hyperconjugative interactions involving the halogen lone pairs (LP(X)) and πC[double bond, length as m-dash]C*, σC[double bond, length as m-dash]C* and σC-X* antibonding orbitals are responsible for the lower (13)C NMR shielding for the cis isomers of the bromine and the iodine compounds than that of the trans isomers.

Conformational Analysis and Electronic Interactions of Some 4'-Substituted-2-ethylthio-phenylacetates.

The conformational analysis of various 4'-substituted-2-ethylthio-phenylacetate compounds bearing the substituents NO2 (1), Cl (2), H (3), Me (4), and OMe (5) was performed using infrared (IR) spectroscopic analysis of the carbonyl stretching band (νCO) supported by B3LYP/6-31G(d,p), NBO, QTAIM, and SM5.42R calculations for compounds 1, 3, and 5. The IR spectra in n-hexane indicate the presence of three components, whose intensities decrease upon increasing frequency. In solvents with high permittivity, while the low intensity component at higher frequency disappears, the relative intensity of the component at the intermediate frequency changes with respect to the lower frequency component with differing trends for the various derivatives. It can be observed that the intensity does not vary for compounds 1 and 2, which bear an electron-withdrawing substituent at 4', while it increases in intensity for compounds 3-5. The computational results predict the presence of three gauche conformers, defined by the orientation of the C-S bond with respect to the carbonyl group, whose intensities and νCO frequencies are in agreement with the experimental results. In solvents with increasing permittivity, the SM5.42R solvation model results reproduce the experimental trend observed for the two components in the low frequency region, while it overestimates the amount of the higher frequency conformer. NBO analysis suggests that all the conformers are stabilized to the same extent in the gauche conformation via σC-S → π*CO and πCO → σ*C-S orbital interactions. The different stability can be attributed to the geometrical arrangement of the C(O)-CH2-S-CH2-CH3 moiety, which assumes a six-membered chair-like geometry in the g1 conformer, a six-membered twisted-chair-like geometry in the g2 conformer, and a seven-membered chair-like ring in the g3 conformer. Quantum theory of atoms in molecules (QTAIM) indicates that the ring geometries were formed and stabilized from short contacts between the oppositely charged carbonyl oxygen and the methylene/methyl hydrogen atoms, which interact through unusual intramolecular electrostatic hydrogen bonding that satisfies the Popelier criteria.

Synthesis and Diels-Alder reactions of a benzo[5]radialene derivative.

Apart from their exotic structure, radialenes have been employed as precursors of more complex polycyclic molecules. In this work we report the synthesis of the first compound having the benzo[5]radialene substructure, starting from simple materials. Such a compound proved to be a convenient diene in Diels-Alder reactions, for the preparation of highly functionalized fluorenes and benzo[b]fluorenes in a quimio- and stereocontrolled fashion.

Conformational analysis and intramolecular interactions of L-proline methyl ester and its N-acetylated derivative through spectroscopic and theoretical studies.

This work reports a detailed study regarding the conformational preferences of L-proline methyl ester (ProOMe) and its N-acetylated derivative (AcProOMe) to elucidate the effects that rule their behaviors, through nuclear magnetic resonance (NMR) and infrared (IR) spectroscopies combined with theoretical calculations. These compounds do not present a zwitterionic form in solution, simulating properly amino acid residues in biological media, in a way closer than amino acids in the gas phase. Experimental (3)JHH coupling constants and infrared data showed excellent agreement with theoretical calculations, indicating no variations in conformer populations on changing solvents. Natural bond orbital (NBO) results showed that hyperconjugative interactions are responsible for the higher stability of the most populated conformer of ProOMe, whereas for AcProOMe both hyperconjugative and steric effects rule its conformational equilibrium.

Phenylalanine and tyrosine methyl ester intramolecular interactions and conformational analysis by (1)H NMR and infrared spectroscopies and theoretical calculations.

Amino acid conformational analysis in solution are scarce, since these compounds present a bipolar zwitterionic structure ((+)H3NCHRCOO(-)) in these media. Also, intramolecular hydrogen bonds have been classified as the sole interactions governing amino acid conformational behavior in the literature. In the present work we propose phenylalanine and tyrosine methyl ester conformational studies in different solvents by (1)H NMR and infrared spectroscopies and theoretical calculations. Both experimental and theoretical results are in agreement and suggest that the conformational behavior of the phenylalanine and tyrosine methyl esters are similar and are dictated by the interplay between steric and hyperconjugative interactions.

Studies on the s-cis-trans isomerism for some furan derivatives through IR and NMR spectroscopies and theoretical calculations.

The s-cis-trans isomerism of two furan derivatives [2-acetyl- (AF) and 2-acetyl-5-methylfuran, (AMF)] was analyzed, using data from the deconvolution of their carbonyl absorption band in two solvents (CH(2)Cl(2) and CH(3)CN). These infrared data showed that the O,O-trans conformers predominate in the less polar solvent (CH(2)Cl(2)), but these equilibria change in a more polar solvent (CH(3)CN) leading to a slight predominance of the O,O-cis conformers, in agreement with the theoretical calculations. The later results were obtained using B3LYP-IEFPCM/6-31++g(3df,3p) level of theory, which taking into account the solvent effects at IEFPCM (Integral Equation Formalism Polarizable Continuum Model). Low temperature (13)CNMR spectra in CD(2)Cl(2) (ca. -75 °C) showed pairs of signals for each carbon, due to the known high energy barrier for the cis-trans interconversion leading to a large predominance of the trans isomers, which decreases in acetone-d(6). This was confirmed by their (1)HNMR spectra at the same temperatures. Moreover, despite the larger hyperconjugative interactions for the O,O-cis isomers, obtained from NBO data, these isomers are destabilized by the their Lewis energy.

Unexpected geometrical effects on paramagnetic spin-orbit and spin-dipolar 2J(FF) couplings.

The second-rank tensor character of the paramagnetic spin-orbit and spin-dipolar contributions to nuclear spin-spin coupling constants is usually ignored when NMR measurements are carried out in the isotropic phase. However, in this study it is shown that isotropic (2)J(FF) couplings strongly depend on the relative orientation of the C-F bonds containing the coupling nuclei and the eigenvectors of such tensors. Predictions about such effect are obtained using a qualitative approach based on the polarization propagator formalism at the RPA, and results are corroborated performing high-level ab initio spin-spin coupling calculations at the SOPPA(CCSD)/EPR-III//MP2/EPR-III level in a model system. It is highlighted that no calculations at the RPA level were carried out in this work. The quite promising results reported in this paper suggest that similar properties are expected to hold for the second-rank nuclear magnetic shielding tensor.

Stereochemical dependence of 3JCH coupling constants in 2-substituted 4-t-butyl-cyclohexanone and their alcohol derivatives.

Theoretical and experimental studies on (3)J(C2H6eq) NMR spin-spin coupling constants in both the 2-X-4-t-butyl-cyclohexanone (X = H, CH(3), F, Cl, and Br) and in their alcohol derivatives series are reported. Results thus found are rationalized in terms of the transmission of the Fermi contact contribution to such couplings. To this end, dependencies of (3)J(C2H6eq) couplings versus the C(2)-C(1)-C(6) angle are compared in both series for equatorial and axial X orientations. The main trend is described in terms of the rear lobes interaction. Besides, for X = halogen atom in equatorial orientation a rather strong interaction between oxygen and halogen lone pairs is observed, and its influence on (3)J(C2H6eq) couplings is discussed and rationalized in terms of different Fermi contact transmission pathways.

Conformational preferences for some 5-substituted 2-acetylthiophenes through infrared spectroscopy and theoretical calculations.

The s-cis-trans isomerisms of some derivatives of thiophene (2-acetyl, AT; 2-acetyl-5-bromo, ABT and 2-acetyl-5-chloro, ACT) were analyzed, using data from deconvolution of their carbonyl absorption bands in two solvents (CCl4 and CHCl3). These infrared data showed that the O,S-cis conformer largely predominates in the studied solvents and that the same occurs in the gas phase, as observed from theoretical calculations. The latter results were obtained using B3LYP/6-311++G(3df,3p) and MP2/6-311++G(3df,3p) levels of theory, with zero-point energy correction. Moreover, the use of the IEFPCM (Integral Equation Formalism Polarizable Continuum Model) to take into account the solvent effects, using the same levels of theory, confirmed the results observed from infrared data. Low temperature 13C NMR spectra in CS2/CD2Cl2 (-90 °C) and in acetone-d6 (-80°C) did not show pairs of signals for each carbon, due to the known low energy barrier (∼8 kcal mol(-1)) for the cis-trans interconversion. Data from NBO calculations show that the nO(2)→σS-C5* and nO(2)→σC2-C3* interactions occur only in the O,S-cis isomer and can explain its conformational preference.

Experimental, SOPPA(CCSD), and DFT analysis of substitutent effects on NMR 1JCF coupling constants in fluorobenzene derivatives.

Interesting insight into the electronic molecular structure changes associated with substituent effects on the Fermi contact (FC) and paramagnetic spin-orbit (PSO) terms of (1)J(CF) NMR coupling constants (SSCCs) in o-X-, m-X-, and p-X-fluorobenzenes (X = NH(2); NO(2)) is presented. The formulation of this approach is based on the influence of different conjugative and hyperconjugative interactions on a second-order property, which can be qualitatively predicted if it is known how they affect the main virtual excitations entering into that second-order property. A set of consistent approximations are introduced in order to analyze the behavior of occupied and virtual orbitals, which define some experimental trends for (1)J(CF) spin-spin coupling constants. In addition, DFT hybrid functionals were used, and a similar degree of confidence to compute the (1)J(CF) with those observed for the SOPPA(CCSD) method was obtained. The (1)J(CF) SSCCs for ezetimibe, a commercially fluorinated drug used to reduce cholesterol levels, were measured and DFT-calculated, and the qualitative approach quoted above was applied. As a byproduct, a possible method to determine experimentally a significant PSO contribution to (1)J(CF) SSCCs is discussed.