Influence of substituents on the through-space shielding of aromatic rings

A series of naphthalene derivatives, bearing a methyl group and a substituted phenyl ring in a 1,8-relationship, have been synthesized. The chemical shifts of the protons of the methyl group, which are pointed toward the shielding zone of the phenyl ring, were monitored as the phenyl substituents were varied. This work indicates that the shielding effect of the phenyl ring is not so severely altered by the substituents as to significantly influence the chemical shift of the methyl group. Nonetheless, within the small changes observed experimentally, there appears to be a tendency for electron-withdrawing X to shift the methyl signal downfield, whereas electron-donating X-groups cause a more upfield shift. Polarization and field effects are discussed as possible causes for this phenomenon. Chemical shifts computed for selected members of the series, using the recently published procedures of Rablen and Bally, are in agreement with the experimentally observed trends.     

The change of the proton magnetic shielding in red- and blue-shifted linear hydrogen-bonded complexes

The change in the proton magnetic shielding constant of FH and FArH on the formation of the vibrationally red-shifted FH... Rg and blue-shifted FArH... Rg (Rg = Ne, Ar). complexes was determined by GIAO ab initio computations at various levels of theory. The blue-shifted FArH... N₂ and red-shifted FArH... P₂ complexes were also studied. The characteristic downfield shift of the isotropic proton magnetic resonance in red-shifted hydrogen-bonded complexes is smaller in the blue-shifted complexes. In FArH... Ne and FArH... N₂ the proton NMR actually shifts to higher fields on complexation. These results are rationalized by considering the changes in the magnetic and electric contributions to the proton shielding in FH and FArH.     

Carbon chemical shift tensor components in quinolines and quinoline N-oxides

Chemical shift calculations are carried out for the quinoline carbons in 1,8-bis(2-isopropyl-4-quinolyl)naphthalene, 2-isopropylquinoline, amodiaquine, chloroquine, and quinine and the N-oxide of each compound. Ab initio calculations of the isotropic shielding values are in agreement with experimental chemical shifts. The calculations indicate that changes to the principal components of the shielding tensor upon N-oxidation are similar for each compound. Carbons 2, 4, 8, and 10 are largely shielded in each case as the nitrogen is oxidized. For C2, C4, and C10, this shielding is due to a large change in sigma11 and/or sigma22, indicating a change in pi-electron density. For C8, the large shielding change is due mainly to a change in sigma33, indicating a change in sigma-electron density. Upon examination and comparison of the calculated 13C shielding tensor components in the antimalarial drugs versus those in unsubstituted quinolines, it is found that amodiaquine and chloroquine have increased pi-electron density in the ring containing the amino side chain and quinine has increased pi-electron density in the opposite ring, containing the methoxy substituent.     

Molecular orbital studies of the NMR hydrogen bond shift

Magnetic shielding constants are calculated for the protons in XOH and XOH…OH₂ (XH, CH₃, NH₂, OH and F) molecules using a slightly extended set of atomic functions modified by gauge factors. These results are used to determine theoretical values for the NMR hydrogen bond shifts in the XOH…OH₂ systems. Such theoretical data are consistent with the few available experimental data. An analysis of the theoretical results reveals that there are three major types of shielding contribution to the NMR hydrogen bond shift; (a) a deshielding change due to the variation of the local currents on the hydrogen bonded proton; (b) a reduction in shielding from currents localized on the oxygen atom of the proton donor; (c) a deshielding contribution from currents induced on the oxygen atom of the proton acceptor. Except for the water dimer, contributions (a), (b) and (c) are of comparable importance for changes in isotropic shielding. For (H₂O)₂ contributions (a) and (c) are somewhat more important than contribution (b). Contribution (c) is almost totally responsible for the changes in the anistropies of the shielding tensors associated with the hydrogen bonded protons. The proton shielding anisotropy changes which occur on hydrogen bond formation are generally much larger than the corresponding variations in the isotropic values of the shielding tensors. This suggests that proton magnetic shielding anisotropies may be more sensitive measures of features of hydrogen bonding than are isotropic proton shielding constants.     

Spectroscopic studies on methyl torsional behavior in 1-methyl-2(1H)-pyridone, 1-methyl-2(1H)-pyridinimine, and 3-methyl-2(1H)-pyridone. I. Excited state

The laser induced fluorescence excitation and dispersed fluorescence spectra of three nitrogen heterocyclic molecules 1-methyl-2(1H)pyridone (1MPY), 1-methyl-2(1H)pyridinimine (1MPI), and 3-methyl-2(1H)pyridone (3MPY) have been studied under supersonic jet cooled condition. The methyl torsional and some low frequency vibrational transitions in the fluorescence excitation spectrum were assigned for 1MPY. These new assignments modify the potential parameters to the methyl torsion reported earlier. Some striking similarities exist between the torsional and vibrational transitions in the fluorescence excitation spectra of 1MPY and 1MPI. Apart from pure torsional transitions, a progression of vibration-torsion combination bands was observed for both these molecules. The excitation spectrum of 3MPY resembles the spectrum of its parent molecule, 2-pyridone. The barrier height of the methyl torsion in the excited state of 3MPY is highest amongst all these molecules, whereas the barrier in 1MPI is higher than that of 1MPY. To get an insight into the methyl torsional barrier for these molecules, results of the ab initio calculations were compared with the experimental results. It was found that the conformation of the methyl group undergoes a 60 degrees rotation in the excited state in all these molecules with respect to their ground state conformation. This phase shift of the excited state potential is attributed to the pi*-sigma* hyperconjugation between the out-of-plane hydrogen of the methyl group and the molecular frame. It has been inferred that the change in lowest unoccupied molecular orbital energy plays the dominant role in the excited state barrier formation.     

Calculations of the contribution of ring currents to the chemical shielding anisotropy

Ring currents can exert a large effect upon the chemical shielding of NMR resonances. The analytical expression developed by Waugh and Fessenden (Waugh, J. S.; Fessenden, R. W. J. Am. Chem. Soc. 1957, 79, 846) and Johnson and Bovey (Johnson, C. E.; Bovey, F. A. J. Chem. Phys. 1957, 29, 1012) only quantifies the contribution of ring currents to the isotropic component of the shielding tensor. In the work described here an additional analytical expression is developed so that the contribution of ring currents to the full shielding tensor can be calculated, allowing an estimate of the influence of ring currents upon the chemical shielding anisotropy (CSA, Deltasigma). To test that this pair of analytical expressions can provide a reasonable estimate of the contribution of ring currents to the full shielding tensor a series of density functional calculations (DFT) were carried out. A shielding tensor in a model compound was calculated in two distinct ways. For the first series, DFT shielding calculations of the model compound were carried out in the presence of a benzene ring. For the second series a ring current contribution to the shielding tensor was calculated via the new expressions, and this was added to the result of a DFT shielding calculation which used in place of benzene the nonaromatic analogue 1,3 cyclohexadiene. The two series of results proved to be in excellent agreement. The pair of analytical expressions are used to calculate ring current contributions to the CSA (Deltasigma) of 1H(N) backbone amide resonances in a structure of the second type 2 module from the protein fibronectin. Significant CSA variations are predicted in particular for the 1H(N) of G42 which is most likely involved in a N-H...tpi aromatic hydrogen bond.     

Structural relaxation upon internal rotation in cis-methyl nitrite,CH3 ONO

The ab initio SCF gradient method has been used to obtain changes of bond lengths and valence angles upon internal rotation of CH₃ and NO groups in cis-methyl nitrite. The data for methyl torsion are confirmed by comparison of calculated and observed shifts of rotational constants in the first methyl torsional state.     

Origin of threefold symmetric torsional potential of methyl group in 4-methylstyrene

To understand the effect of the para position vinyl group substitution in toluene on methyl torsion, we investigated 4-methylstyrene, a benchmark molecule with an extended pi conjugation. The assignment for a 33 cm(-1) band in the excitation spectrum to the 3a(2) torsional transition, in addition to the assignments suggested previously for the other bands in the excitation spectrum, leads to the model potentials for the ground as well as excited states with V(3) (")=19.6 cm(-1), V(6) (")=-16.4 cm(-1) and V(3) (')=25.6 cm(-1), V(6) (')=-30.1 cm(-1), respectively. These potentials reveal that both in ground and excited states, the methyl group conformations are staggered with a 60 degrees phase shift between them. MP2 ab initio calculations support the ground state conformations determined from experiments, whereas Hartree-Fock calculations fail to do so. The origin of the modified ground state potential has been investigated by partitioning the barrier energy using the natural bond orbital (NBO) theoretical framework. The NBO analysis shows that the local delocalization (bond-antibond hyperconjugation) interactions of the methyl group with the parent molecule is sixfold symmetric. The threefold symmetric potential, on the other hand, stems from the interaction of the vinyl group and the adjacent ring pi bond. The threefold symmetric structural energy arising predominantly from the pi electron contribution is the barrier forming term that overwhelms the antibarrier contribution of the delocalization energy. The observed 60 degrees phase shift of the excited state potential is attributed to the pi(*)-sigma(*) hyperconjugation between out of plane hydrogens of the methyl group and the benzene ring.     

A Raman spectroscopic study of the low-frequency vibrations in anisole and anisole-d3

Low-frequency Raman spectra of solid anisole and of solid anisole-d₃ have been recorded at 130 K. The phenyl torsion observed at 148 cm^?1 is shifted to 133 cm^?1 upon deuteration of the methyl group. The twofold torsional barriers calculated from these frequencies are 4033 ± 110 cm^?1 and 4094 ± 123 cm^?1 indicating that coupling to other low-frequency modes in both cases is of the same order of magnitude. The methyl torsional mode was observed at 285 cm^?1 in the spectrum of solid anisole and at 183 cm^?1 in the spectrum of anisole-d₃. The threefold barriers calculated using these frequencies are 1847 ± 20 cm^?1 and 1465 ± 18 cm^?1 respectively. These barrier values indicate that the methyl torsion is coupled to another low-frequency mode. A doublet centered at 230 cm^?1 in anisole is shifted to 245 cm^?1 in anisole-d₃; it is proposed that this is due to a ring mode coupled to the methyl torsion. The splitting is interpreted as an example of Davydov splitting.     

Origin of methyl torsional barrier in 1-methyl-2(1H)-pyridinimine and 3-methyl-2(1H)-pyridone: II. Ground state

To get the insight into the electronic structure-methyl torsion correlation in nitrogen heterocyclic molecules, a comparative study on torsion of the methyl group in 1-methyl-2(1H)pyridone (1MPY), 1-methyl-2(1H)pyridinimine (1MPI), and 3-methyl-2(1H)pyridone (3MPY) was carried out using ab initio calculations. To understand the barrier forming mechanism in the ground state and its consequence on the molecular structure, the ground state torsional potential has been investigated by partitioning the barrier energy using the natural bond orbital (NBO) theoretical framework. The NBO analysis reveals that the delocalization energy is the barrier forming term whereas the Lewis energy is always antibarrier for all these molecules. To get further insight into the effect of local electronic structure on the methyl torsional barrier, the individual bond-antibond interactions and structural energy contributions have been investigated. It was found that when the bond order difference between the vicinal bonds does not change appreciably during the course of methyl rotation, the local electronic interactions with the methyl group do not play any decisive role in barrier formation as observed in the case of 1MPY and 1MPI. In these cases, it is the skeletal relaxation during methyl rotation that plays an important role in determining the barrier. On the other hand, if the bond order change is appreciable as is the case for 3MPY, the local interactions alone suffice to describe the origin of the torsional barrier of the methyl group.     

Theoretical study on the phenyl torsional potentials of trans-diphenyldiphosphene

The phenyl torsional potentials of trans-diphenyldiphosphene ( trans-phosphobenzene; t-DPP), which is an analogue of trans-azobenzene ( t-AZB), have been examined by means of ab initio complete active space self-consistent field (CASSCF) calculations. Though the electronic structures of t-DPP are similar to those of t-AZB, the phenyl torsional potentials are different from each other. In S 0, the potential energy curve of t-DPP has double minima at nonplanar conformations with C 2 and C i symmetries, while that of t-AZB has only minimum at a planar conformation with C 2 h . In S 1, the phenyl torsion of t-AZB is impeded from a planar geometry more than that in S 0. On the other hand, the phenyl torsion of t-DPP is promoted so that the phenyl groups are perpendicularly twisted against the PP double bond around the Franck-Condon region. Comments on the experimental findings of realistic diphosphenes protected by bulky substituents are also made.     

A nuclear magnetic resonance study of hindered rotation in 8-phenylpurines

In the PMR spectrum of 8-phenylpurines, the multiplet of the o-protons appears downfield of the multiplet, characteristic for m,p-protons. The separation of the centres of these two signals (Δ-value) diminishes with increasing steric interference between the phenyl ring and substituents in the imidazole moiety. The contribution of the purine ring current to the chemical shifts of the aromatic protons was calculated according to the theory of Johnson and Bovey, and the torsion angles θ between the phenyl ring and the plane of the purine system were derived. For 8-phenylpurines with an NH-group in the imidazole ring, θ is 10–15°; for compounds with an N-methyl group in this ring, θ ≈ 35–45°; in 3,9-dimethyl derivatives, Δ becomes zero, while θ is about 50°.     

High resolution mass spectrometric study of organosilicon compounds. Siloxazolidones: Cyclized amino acid-silane derivatives

High resolution mass spectra have been obtained for a series of methyl, ethyl and phenyl substituted siloxazolidones (cyclic compounds derived from the condensation of organosilane derivatives with amino acids). The effects on the mass spectra of these compounds upon substitution at the saturated ring carbon and at the silicon atom, the migratory nature of the phenyl group on nitrogen, and theextent of biphenyl radical ion formation in the skeletal rearrangement processes have been examined.     

Substituent and Solvent Effects on the Excited State Deactivation Channels in Anils and Boranils

Differently substituted anils (Schiff bases) and their boranil counterparts lacking the proton‐transfer functionality have been studied using stationary and femtosecond time‐resolved absorption, fluorescence, and IR techniques, combined with quantum mechanical modelling. Dual fluorescence observed in anils was attributed to excited state intramolecular proton transfer. The rate of this process varies upon changing solvent polarity. In the nitro‐substituted anil, proton translocation is accompanied by intramolecular electron transfer coupled with twisting of the nitrophenyl group. The same type of structure is responsible for the emission of the corresponding boranil. A general model was proposed to explain different photophysical responses to different substitution patterns in anils and boranils. It is based on the analysis of changes in the lengths of CN and CC bonds linking the phenyl moieties. The model allows predicting the contributions of different channels that involve torsional dynamics to excited state depopulation.     

Enthalpic and entropic contributions to the conformational free energies of methylthio, methylsulfinyl, methylsulfonyl, phenylthio, phenylsulfinyl, and phenylsulfonyl

A variable-temperature NMR study of (cis-4-methylcyclohexyl)methyl sulfide (1), sulfoxide (2), and sulfone (3), as well as (cis-4-methylcyclohexyl)phenyl sulfide (4), sulfoxide (5), and sulfone (6) allowed determination of the thermodynamic parameters, DeltaH degrees and DeltaS degrees, for the title groups. Reproduction of the experimental results with Allinger's MM3 program was successfully accomplished in the case of the sulfoxide and sulfide groups. Nevertheless, modification of the original force field torsional parameters was required in order to adequately reproduce the experimentally observed behavior of the sulfonyl derivatives. Rationalization of the enthalpic and entropic contributions to DeltaG degrees [S(O)(n)()R, n = 0, 1, 2; R = CH(3), Ph] is advanced in terms of the steric characteristics of these sulfur-containing groups and the resulting rotameric populations in the axial and equatorial monosubstituted cyclohexanes.     

77Se shielding tensors of diphenyl diselenide, comparison of the results from CP/MAS NMR spectroscopy and IGLO calculations

The cross-polarization/magic-angle-spinning (CP/MAS) ⁷⁷SeNMR experiment of Ph-Se-Se-Ph affords two signal series with isotropic chemical shifts at δ_iso = 425 and 350. IGLO calculations allow to assign the ⁷⁷Se signals and to predict the orientation of the shielding tensors. The different chemical shifts can be explained by different torsion angles Se-Se-C^ipso-C^ortho which produce different β effects of the phenyl rings upon the respective next but one selenium atom. Received: 24 April 1996 / Accepted: 15 May 1996     

A repertoire of pyridinium-phenyl-methyl cross-talk through a cascade of intramolecular electrostatic interactions

Direct intramolecular cation-pi interaction between phenyl and pyridinium moieties in 1a(+) has been experimentally evidenced through pH-dependent (1)H NMR titration. The basicity of the pyridinyl group (pK(a) 2.9) in 1a can be measured both from the pH-dependent chemical shifts of the pyridinyl protons as well as from the protons of the neighboring phenyl and methyl groups as a result of electrostatic interaction between the phenyl and the pyridinium ion in 1a(+) at the ground state. The net result of this nearest neighbor electrostatic interaction is that the pyridinium moiety in 1a becomes more basic (pK(a) 2.92) compared to that in the standard 2a (pK(a) 2.56) as a consequence of edge-to-face cation (pyridinium)-pi (phenyl) interaction, giving a free energy of stabilization (DeltaDeltaG(o)pKa) of -2.1 kJ mol(-1). The fact that the pH-dependent downfield shifts of the phenyl and methyl protons give the pK(a) of the pyridine moiety of 1a also suggests that the nearest neighbor cation (pyridinium)-pi (phenyl) interaction also steers the CH (methyl)-pi (phenyl) interaction in tandem. This means that the whole pyridine-phenyl-methyl system in 1a(+) is electronically coupled at the ground state, cross-modulating the physicochemical property of the next neighbor by using the electrostatics as the engine, and the origin of this electrostatics is a far away point in the molecule-the pyridinyl-nitrogen. The relative chemical shift changes and the pK(a) differences show that the cation (pyridinium)-pi (phenyl) interaction is indeed more stable (DeltaDeltaG(o)pKa = -2.1 kJ mol(-1)) than that of the CH (methyl)-pi (phenyl) interaction (DeltaDeltaG(o)pKa = -0.8 kJ mol(-1)). Since the pK(a) of the pyridine moiety in 1a is also obtained through the pH-dependent shifts of both phenyl and methyl protons, it suggests that the net electrostatic mediated charge transfer from the phenyl to the pyridinium and its effect on the CH (methyl)-pi (phenyl) interaction corresponds to DeltaG(o)pKa of the pyridinium ion (approximately 17.5 kJ mol(-1)), which means that the aromatic characters of the phenyl and the pyridinium rings in 1a(+) have been cross-modulated owing to the edge-to-face interaction proportional to this DeltaG(o)pKa change.     

The methyl and methoxyl torsional modes and the lattice vibration in the low-frequency Raman spectrum of 1,4-dimethoxybenzene

The low-frequency (10–450 cm^?1) Raman spectra of solid (at 300 K and 130 K) and liquid (at 335 K) 1,4-dimethoxybenzene-d₀ and 1,4-dimethoxybenzene-d₅ have been measured. The methyl nad methoxyl torsional transitions have been identified and the corresponding torsional barriers calculated. Upon deuleration the methyl torsional barrier is reduced by 450 cm^?1, implying a coupling between the methyl torsion and a low-frequency ring mode. As far as the torsions are considered, the internal dynamic situation in 1,4-dimethoxybezene resembles that in amisole. A tentative assignment of the observed lattice bands in given. Certain changes in the spectrum when going from the solid to the melt are attributed to the coexistence of both cis and trans conformers in the liquid state.     

Molecular dynamics investigation of bent-core molecules on a water surface

Molecular dynamics simulations are carried out for bent-core molecules at water surfaces. The water surface is shown to alter the equilibrium molecular structure significantly by causing a different class of torsional states to become more favorable. The equilibrium structure is also altered by the substitution of chlorine atoms for hydrogen atoms on the central phenyl ring in that this substitution forces the bent core to remain in a single torsional state rather than be delocalized among several torsional states. The consequences of these structural changes on the chirality and packing of these molecules on water surfaces are discussed.     

Carbon-13 NMR shielding in the twenty common amino acids: comparisons with experimental results in proteins

We have used ab initio quantum chemical techniques to compute the (13)C(alpha) and (13)C(beta) shielding surfaces for the 14 amino acids not previously investigated (R. H. Havlin et al., J. Am. Chem. Soc. 1997, 119, 11951-11958) in their most popular conformations. The spans (Omega = sigma(33) - sigma(11)) of all the tensors reported here are large ( approximately 34 ppm) and there are only very minor differences between helical and sheet residues. This is in contrast to the previous report in which Val, Ile and Thr were reported to have large ( approximately 12 ppm) differences in Omega between helical and sheet geometries. Apparently, only the beta-branched (beta-disubstituted) amino acids have such large CSA span (Omega) differences; however, there are uniformly large differences in the solution-NMR-determined CSA (Deltasigma = sigma(orth) - sigma(par)) between helices and sheets in all amino acids considered. This effect is overwhelmingly due to a change in shielding tensor orientation. With the aid of such shielding tensor orientation information, we computed Deltasigma values for all of the amino acids in calmodulin/M13 and ubiquitin. For ubiquitin, we find only a 2.7 ppm rmsd between theory and experiment for Deltasigma over an approximately 45 ppm range, a 0.96 slope, and an R(2) = 0.94 value when using an average solution NMR structure. We also report C(beta) shielding tensor results for these same amino acids, which reflect the small isotropic chemical shift differences seen experimentally, together with similar C(beta) shielding tensor magnitudes and orientations. In addition, we describe the results of calculations of C(alpha), C(beta), C(gamma)1, C(gamma)2, and C(delta) shifts in the two isoleucine residues in bovine pancreatic trypsin inhibitor and the four isoleucines in a cytochrome c and demonstrate that the side chain chemical shifts are strongly influenced by chi(2) torsion angle effects. There is very good agreement between theory and experiment using either X-ray or average solution NMR structures. Overall, these results show that both C(alpha) backbone chemical shift anisotropy results as well as backbone and side chain (13)C isotropic shifts can now be predicted with good accuracy by using quantum chemical methods, which should facilitate solution structure determination/refinement using such shielding tensor surface information.