On the configuration of five-membered rings: a spin-spin coupling constant approach

Five-membered rings are clearly among the most common structural motifs found in chemistry and biology. Nevertheless, the configuration of conformationally mobile five-membered rings is often difficult to assign from nuclear magnetic resonance (NMR) data. A simple, reliable, and efficient approach for the stereochemical analysis of five-membered rings based on the measurement of NMR coupling constants is presented. Density functional theory calculations using representative conformations of the full conformational space available to rings with different substitution patterns were used to identify differences between the accessible coupling constant values for cis and trans relative orientations of the substituents. The calculations were assessed experimentally using NMR data obtained from a number of models. This approach can be easily used to analyze different five-membered rings, such as oxolanes, cyclopentanes, furanosides and pyrrolidines, and their relative configuration can be determined without the need for making further conformational considerations.     

Characterization of persistent intramolecular C-H...X(N,O) bonds in solid state and solution

The formation of intramolecular CH...X(N,O) bonds and their persistence in solution were studied by X-ray crystallography and NMR techniques in two different rotamers of a molecule containing the ortho-carborane cage, an amide group and a quinoline ring. Experimental data were confirmed by theoretical ab initio calculations. From the resolved structure of the two forms of this potentially active drug for boron neutron capture therapy, accurate bonding and geometric parameters were extracted for this non-classic hydrogen interaction, and their strength was calculated. These findings provided new insight in the theory of CH...X bonds, which appear stronger and less rare than it was previously thought.     

Polymorphism of N,N'-diacetylbiuret studied by solid-state 13C and 15N NMR spectroscopy, DFT calculations, and X-ray diffraction

The molecular configuration and crystal structure of solid polycrystalline N,N′′‐diacetylbiuret (DAB), a potential nitrogen‐rich fertilizer, have been analyzed by a combination of solid‐ and liquid‐state NMR spectroscopy, X‐ray diffraction, and DFT calculations. Initially a pure NMR study (“NMR crystallography”) was performed as available single crystals of DAB were not suitable for X‐ray diffraction. Solid‐state ¹³C NMR spectra revealed the unexpected existence of two polymorphic modifications (α‐ and β‐DAB) obtained from different chemical procedures. Several NMR techniques were applied for a thorough characterization of the molecular system, revealing chemical shift anisotropy (CSA) tensors of selected nuclei in the solid state, chemical shifts in the liquid state, and molecular dynamics in the solid state. Dynamic NMR spectroscopy of DAB in solution revealed exchange between two different configurations, which raised the question, is there a correlation between the two different configurations found in solution and the two polymorphic modifications found in the solid state? By using this knowledge, a new crystallization protocol was devised which led to the growth of single crystals suitable for X‐ray diffraction. The X‐ray data showed that the same symmetric configuration is present in both polymorphic modifications, but the packing patterns in the crystals are different. In both cases hydrogen bonds lead to the formation of planes of DAB molecules. Additional symmetry elements, a two‐fold screw in the case of α‐DAB and a c‐glide plane in the case of β‐DAB, lead to a more symmetric (α‐DAB) or asymmetric (β‐DAB) intermolecular hydrogen‐bonding pattern for each molecule.     

First investigation of non-classical dihydrogen bonding between an early transition-metal hydride and alcohols: IR, NMR, and DFT approach

The interaction of [NbCp(2)H(3)] with fluorinated alcohols to give dihydrogen-bonded complexes was studied by a combination of IR, NMR and DFT methods. IR spectra were examined in the range from 200-295 K, affording a clear picture of dihydrogen-bond formation when [NbCp(2)H(3)]/HOR(f) mixtures (HOR(f) = hexafluoroisopropanol (HFIP) or perfluoro-tert-butanol (PFTB)) were quickly cooled to 200 K. Through examination of the OH region, the dihydrogen-bond energetics were determined to be 4.5+/-0.3 kcal mol(-1) for TFE (TFE = trifluoroethanol) and 5.7+/-0.3 kcal mol(-1) for HFIP. (1)H NMR studies of solutions of [NbCp(2)H(2)(B)H(A)] and HFIP in [D(8)]toluene revealed high-field shifts of the hydrides H(A) and H(B), characteristic of dihydrogen-bond formation, upon addition of alcohol. The magnitude of signal shifts and T(1) relaxation time measurements show preferential coordination of the alcohol to the central hydride H(A), but are also consistent with a bifurcated character of the dihydrogen bonding. Estimations of hydride-proton distances based on T(1) data are in good accord with the results of DFT calculations. DFT calculations for the interaction of [NbCp(2)H(3)] with a series of non-fluorinated (MeOH, CH(3)COOH) and fluorinated (CF(3)OH, TFE, HFIP, PFTB and CF(3)COOH) proton donors of different strengths showed dihydrogen-bond formation, with binding energies ranging from -5.7 to -12.3 kcal mol(-1), depending on the proton donor strength. Coordination of proton donors occurs both to the central and to the lateral hydrides of [NbCp(2)H(3)], the former interaction being of bifurcated type and energetically slightly more favourable. In the case of the strong acid H(3)O(+), the proton transfer occurs without any barrier, and no dihydrogen-bonded intermediates are found. Proton transfer to [NbCp(2)H(3)] gives bis(dihydrogen) [NbCp(2)(eta(2)-H(2))(2)](+) and dihydride(dihydrogen) complexes [NbCp(2)(H)(2)(eta(2)-H(2))](+) (with lateral hydrides and central dihydrogen), the former product being slightly more stable. When two molecules of TFA were included in the calculations, in addition to the dihydrogen-bonded adduct, an ionic pair formed by the cationic bis(dihydrogen) complex [NbCp(2)(eta(2)-H(2))(2)](+) and the homoconjugated anion pair (CF(3)COO...H...OOCCF(3))(-) was found as a minimum. It is very likely that these ionic pairs may be intermediates in the H/D exchange between the hydride ligands and the OD group observed with the more acidic alcohols in the NMR studies.     

Torsional angular dependence of 1J(Se,Se) and Fermi contact control of 4J(Se,Se): analysis of nJ(Se,Se) (n=1-4) based on molecular orbital theory

(n)J(Se,Se) (n=1-4) nuclear couplings between Se atoms were analyzed by using molecular orbital (MO) theory as the first step to investigating the nature of bonded and nonbonded (n)J(Se,Se) interactions between Se atoms. The values were calculated by employing Slater-type triple xi basis sets at the DFT level, which were applied to structures optimized with the Gaussian 03 program. The contribution from each occupied MO (psi(i)) and psi(i)-->psi(a) (psi(a)=unoccupied MO) transition was evaluated separately. 1J(Se,Se) was calculated for the MeSeSeMe model compound, which showed a typical dependence on the torsion angle (phi(C(Me)SeSeC(Me))). This dependence explains the small values (< or =64 Hz) of 1Jobsd(Se,Se) observed for RSeSeR' and large values (330-380 Hz) of 1Jobsd(Se,Se) observed for 4-substituted naphtho[1,8-c,d]-1,2-diselenoles, which correspond to synperiplanar diselenides. The HOMO-->LUMO and HOMO-1-->LUMO transitions contribute the most to 1J(Se,Se) at phi=0 and 180 degrees to give large values of 1J(Se,Se), whereas various transitions contribute and cancel each other out at phi=90 degrees to give small values of 1J(Se,Se). Large 4Jobsd(Se,Se) values were also observed in the nonbonded Se...Se, Se...Se=O, and O=Se...Se=O interactions at naphthalene 1,8-positions. The Fermi contact (FC) term contributes significantly to 4J(Se,Se), whereas the paramagnetic spin-orbit (PSO) term contributes significantly to 1J(Se,Se). 2J(Se,Se) and 3J(Se,Se) were analyzed in a similar manner and a torsional angular dependence was confirmed for 3J(Se,Se). Depending on the structure, the main contribution to (n)J(Se,Se) (n=2, 3) is from the FC term, with a lesser contribution from the PSO term. Analysis of each transition enabled us to identify and clearly visualize the origin and mechanism of the couplings.     

Theoretical investigations into the blue-shifting hydrogen bond in benzene complexes.

The benzene...X complexes (X=benzene, antracene, ovalene) were optimised at the MP2/6-31G** level with the C2v symmetry of the complex and planarity of the proton acceptor being preserved. The resulting stabilisation energies amount to 1.2, 2.3 and 2.9 kcal mol(-1), and the C-H bond of the proton donor is contracted by 0.0035, 0.0052 and 0.0055 A, respectively. The contraction is connected with a blue-shift of the C-H stretch vibration frequency. A two-dimensional anharmonic vibration treatment based on a MP2/6-31G** potential energy surface yields the following blue shifts for the complexes studied: 28, 42 and 43 cm(-1). The dominant attraction in the complexes is London dispersion, while the attractive contribution from electrostatic quadrupole-quadrupole interactions is considerably smaller.     

Predicted signs of reduced two-bond spin-spin coupling constants (2hKX-Y) across X-H-Y hydrogen bonds

The reduced two-bond Fermi-contact terms and the reduced spin-spin coupling constants (2h)K(X-Y) across X-H-Y hydrogen bonds for complexes stabilized by C-H-N, N-H-N, O-H-N, F-H-N, C-H-O, O-H-O, F-H-O and C-H-F hydrogen bonds are positive. The NMR Triplet Wavefunction Model (NMRTWM) indicates that the signs of the reduced FC terms and (2h)K(X-Y) are determined by excited triplet states that have an odd number of nodes intersecting the X-Y axis between X and Y, thereby leading to an antiparallel alignment of the nuclear magnetic moments of atoms X and Y.     

Correlation between the 6Li,15N coupling constant and the coordination number at lithium

The 6Li,15N coupling constants of lithium amide dimers and their mixed complexes with n-butyllithium, formed from five different chiral amines derived from (S)-[15N]phenylalanine, were determined in diethyl ether (Et2O), tetrahydrofuran (THF) and toluene. Results of NMR spectroscopy studies of these complexes show a clear difference in 6Li,15N coupling constants between di-, tri- and tetracoordinated lithium atoms. The lithium amide dimers with a chelating ether group exhibit 6Li,15N coupling constants of approximately 3.8 and approximately 5.5 Hz for the tetracoordinated and tricoordinated lithium atoms, respectively. The lithium amide dimers with a chelating thioether group show distinctly larger 6Li,15N coupling constants of approximately 4.4 Hz for the tetracoordinated lithium atoms, and the tricoordinated lithium atoms have smaller 6Li,15N coupling constants, approximately 4.9 Hz, than their ether analogues. In diethyl ether and tetrahydrofuran, mixed dimeric complexes between the lithium amides and n-butyllithium are formed. The tetracoordinated lithium atoms of these complexes have 6Li,15N coupling constants of approximately 4.0 Hz, and the 6Li,15N coupling constants of the tricoordinated lithium atoms differ somewhat, depending on whether the chelating group is an ether or a thioether; approximately 5.1 and approximately 4.6 Hz, respectively. In toluene, mixed trimeric complexes are formed from two lithium amide moieties and one n-butyllithium. In these trimers, two lithium atoms are tricoordinated with 6Li,15N coupling constants of approximately 4.6 Hz and one lithium is dicoordinated with 6Li,15N coupling constants of approximately 6.5 Hz.     

Understanding sterol-membrane interactions part I: Hartree-Fock versus DFT calculations of 13C and 1H NMR isotropic chemical shifts of sterols in solution and analysis of hydrogen-bonding effects

1H and 13C NMR chemical shifts are exquisitely sensitive probes of the local environment of the corresponding nuclei. Ultimately, direct determination of the chemical shifts of sterols in their membrane environment has the potential to reveal their molecular interactions and dynamics, in particular concerning the hydrogen-bonding partners of their OH groups. However, this strategy requires an accurate and efficient means to quantify the influence of the various interactions on chemical shielding. Herein the validity of Hartree-Fock and DFT calculations of the 13C and 1H NMR chemical shifts of cholesterol and ergosterol are compared with one another and with experimental chemical shifts measured in solution at 500 MHz. A computational strategy (definition of basis set, simpler molecular models for the sterols themselves and their molecular complexes) is proposed and compared with experimental data in solution. It is shown in particular that the effects of hydrogen bonding with various functional groups (water as a hydrogen-bond donor and acceptor, acetone) on NMR chemical shifts in CDCl3 solution can be accurately reproduced with this computational approach.     

C-H...O hydrogen bonds in cyclohexenone reveal the spectroscopic behavior of Csp3-H and Csp2-H donors.

C-H...O hydrogen bonds in liquid 2-cyclohexen-1-one are studied to assess the vibrational spectroscopic behavior of the Csp2-H and Csp3-H donors. The presence of a pseudo-isosbestic point in the vC = O region supports the assignment of the two observed bands to two species in equilibrium, considered to be the free and 1:1 associated forms. The values of deltaH degrees =-18.5 +/- 0.6 kJmol(-1) and deltaS degrees = -76 +/- 2 J K(-1) mol(-1) for the dimerization through C-H...O hydrogen bonds were obtained from the dimerization constant at different temperatures. The concentration-dependent intensity of the vCH2 band profile is ascribed to the presence of a blue-shifted band from the hydrogen-bonded Csp3-H group. However, the most surprising result is the absence of concentration- or temperature-dependent intensities in the bands assigned to the stretching modes of the Csp2-H donors.     

Ab initio studies of electron acceptor-donor interactions with blue- and red-shifted hydrogen bonds.

The features of blue- and red-shifted electron acceptor-donor (ACH/B) hydrogen bonds have been compared by using quantum chemical calculations. The geometry, the interaction energy and the vibrational frequencies of both blue- (ACH=F3CH, Cl3CH with B=FCD3) and red-shifted (ACH=F3CH, Cl3CH with B=NH3 and ACH=CH3CCH with B=FCD3, NH3) complexes were obtained by using ab initio MP2(Full)/6-31+G(d,p) calculations with the a priori basis-set superposition error (BSSE) correction method. One-dimensional potential energy and dipole moment functions of the dimensionless normal coordinate Q1, corresponding to the CH stretching mode of ACH, have been compared for both types of complexes. Contributions of separate components of the interaction energy to the frequency shift and the effect of electron charge transfer were examined for a set of intermolecular distances by using the symmetry-adapted perturbation theory (SAPT) approach and natural bond orbitals (NBO) population analysis.     

Contra-thermodynamic behavior in intermolecular hydrogen transfer of alkylperoxy radicals.

Quantum chemical investigation of bimolecular hydrogen transfer involving alkylperoxy radicals, a key reaction family in the free-radical oxidation of hydrocarbons, was performed to establish structure-reactivity relationships. Eight different reactions were investigated featuring four different alkane substrates (methane, ethane, propane and isobutane) and two different alkylperoxy radicals (methylperoxy and iso-propylperoxy). Including forward and reverse pairs, sixteen different activation energies and enthalpies of reaction were used to formulate structure-reactivity relationships to describe this chemistry. We observed that the enthalpy of formation of loosely bound intermediate states has a strong inverse correlation with the overall heat of reaction and that this results in unique contra-thermodynamic behavior such that more exothermic reactions have higher activation barriers. A new structure-reactivity relationship was proposed that fits the calculated data extremely well: E(A)=E(o)+alphaDeltaH(rxn) where alpha=-0.10 for DeltaH(rxn)<0, and alpha=1.10 for DeltaH(rxn)>0 and E(o)=3.05 kcal mol(-1).     

Analysis of Proton NMR in Hydrogen Bonds in Terms of Lone‐Pair and Bond Orbital Contributions

NMR spectroscopic parameters of the proton involved in hydrogen bonding are studied theoretically. The set of molecules includes systems with internal resonance‐assisted hydrogen bonds, internal hydrogen bonds but no resonance stabilization, the acetic acid dimer (AAD), a DNA base pair, and the hydrogen succinate anion (HSA). Ethanol and guanine represent reference molecules without hydrogen bonding. The calculations are based on zero‐point vibrationally averaged molecular structures in order to include anharmonicity effects in the NMR parameters. An analysis of the calculated NMR shielding and J‐coupling is performed in terms of “chemist’s orbitals”, that is, localized molecular orbitals (LMOs) representing lone‐pairs, atomic cores, and bonds. The LMO analysis associates some of the strong de‐shielding of the protons in resonance‐assisted hydrogen bonds with delocalization involving the π‐backbone. Resonance is also shown to be an important factor causing de‐shielding of the OH protons for AAD and HSA, but not for the DNA base pair. Nitromalonamide (NMA) and HSA have particularly strong hydrogen bonds exhibiting signs of covalency in the associated J‐couplings. The analysis results show how NMR spectroscopic parameters that are characteristic for hydrogen bonded protons are influenced by the geometry and degree of covalency of the hydrogen bond as well as intra‐ and intermolecular resonance.     

On differences between hydrogen bonding and improper blue-shifting hydrogen bonding.

Twenty two hydrogen-bonded and improper blue-shifting hydrogen-bonded complexes were studied by means of the HF, MP2 and B3LYP methods using the 6-31G(d,p) and 6--311 ++G(d,p) basis sets. In contrast to the standard H bonding, the origin of the improper blue-shifting H bonding is still not fully understood. Contrary to a frequently presented idea, the electric field of the proton acceptor cannot solely explain the different behavior of the H-bonded and improper blue-shifting H-bonded complexes. Compression of the hydrogen bond due to different attractive forces-dispersion or electrostatics--makes an important contribution as well. The symmetry-adapted perturbation theory (SAPT) has been utilized to decompose the total interaction energy into physically meaningful contributions. In the red-shifting complexes, the induction energy is mostly larger than the dispersion energy while, in the case of blue-shifting complexes, the situation is opposite. Dispersion as an attractive force increases the blue shift in the blue-shifting complexes as it compresses the H bond and, therefore, it increases the Pauli repulsion. On the other hand, dispersion in the red-shifting complexes increases their red shift.     

Identity double-proton transfer in (3Z)-3-hydroxy-1,4-di(quinolin-2-yl)but-3-en-2-one

Although there is a very fast (on the NMR timescale) double-proton transfer in (1Z,3Z)-3-hydroxy-4-quinolin-2-yl-1-quinolin-2(1H)-ylidenbut-3-en-2-one (the product of the condensation of ethyl oxalate with 2lithiomethylquinoline), it is the only species present in chloroform solution. Comparison of the product of condensation of ethyl oxalate with 2lithiomethyl derivatives of pyridine (recent studies) and quinoline (present studies) shows that benzoannulation considerably affects the tautomeric equilibrium. The observed changes are not only quantitative but also qualitative. Moreover, contrary to the proton transfer in the pyridine tautomers, this process is fast in the quinoline tautomers. Comparison of the experimental and ab initio/DFT GIAO-calculated (13)C and (15)N chemical shifts for the transition states in the proton-transfer reactions between (1Z,3Z)- 3-hydroxy-4-quinolin-2-yl-1-quinolin-2(1H)-ylidenbut-3-en-2-one and its tautomers support the theory that a concerted identity reaction takes place between the enolimine-enaminone and enaminone-enolimine tautomeric forms. As a consequence, the most stable tautomeric form, (1Z,3Z)-1,4-di(quinolin-2-yl)buta-1,3-diene-2,3-diol, is not present in the tautomeric mixture.