Calculated 1H NMR Chemical Shifts Research Articles

Solvent-Dependent Structures of Natural Products Based on the Combined Use of DFT Calculations and 1H-NMR Chemical Shifts.

Detailed solvent and temperature effects on the experimental 1H-NMR chemical shifts of the natural products chrysophanol (1), emodin (2), and physcion (3) are reported for the investigation of hydrogen bonding, solvation and conformation effects in solution. Very small chemical shift of │Δδ│ < 0.3 ppm and temperature coefficients │Δδ/ΔΤ│ ≤ 2.1 ppb/K were observed in DMSO-d6, acetone-d6 and CDCl3 for the C(1)–OH and C(8)–OH groups which demonstrate that they are involved in a strong intramolecular hydrogen bond. On the contrary, large chemical shift differences of 5.23 ppm at 298 K and Δδ/ΔΤ values in the range of −5.3 to −19.1 ppb/K between DMSO-d6 and CDCl3 were observed for the C(3)–OH group which demonstrate that the solvation state of the hydroxyl proton is a key factor in determining the value of the chemical shift. DFT calculated 1H-NMR chemical shifts, using various functionals and basis sets, the conductor-like polarizable continuum model, and discrete solute-solvent hydrogen bond interactions, were found to be in very good agreement with the experimental 1H-NMR chemical shifts even with computationally less demanding level of theory. The 1H-NMR chemical shifts of the OH groups which participate in intramolecular hydrogen bond are dependent on the conformational state of substituents and, thus, can be used as molecular sensors in conformational analysis. When the X-ray structures of chrysophanol (1), emodin (2), and physcion (3) were used as input geometries, the DFT-calculated 1H-NMR chemical shifts were shown to strongly deviate from the experimental chemical shifts and no functional dependence could be obtained. Comparison of the most important intramolecular data of the DFT calculated and the X-ray structures demonstrate significant differences for distances involving hydrogen atoms, most notably the intramolecular hydrogen bond O–H and C–H bond lengths which deviate by 0.152 tο 0.132 Å and 0.133 to 0.100 Å, respectively, in the two structural methods. Further differences were observed in the conformation of –OH, –CH3, and –OCH3 substituents.

Hydrogen Atomic Positions of O-H···O Hydrogen Bonds in Solution and in the Solid State: The Synergy of Quantum Chemical Calculations with ¹H-NMR Chemical Shifts and X-ray Diffraction Methods.

The exact knowledge of hydrogen atomic positions of O–H···O hydrogen bonds in solution and in the solid state has been a major challenge in structural and physical organic chemistry. The objective of this review article is to summarize recent developments in the refinement of labile hydrogen positions with the use of: (i) density functional theory (DFT) calculations after a structure has been determined by X-ray from single crystals or from powders; (ii) 1H-NMR chemical shifts as constraints in DFT calculations, and (iii) use of root-mean-square deviation between experimentally determined and DFT calculated 1H-NMR chemical shifts considering the great sensitivity of 1H-NMR shielding to hydrogen bonding properties.

Interplay of Noncovalent Interactions in Ribbon-like Guanosine Self-Assembly: An NMR Crystallography Study

An NMR crystallography study shows how intermolecular N–H···O, N–H···N, O–H···N, O–H···O, and CH−π interactions stabilize the ribbon-like supramolecular structures of three different guanosine derivatives: guanosine dihydrate (G), 3′,5′-O-dipropanolyl deoxyguanosine (dG(C3)2), and 3′,5′-O-isopropylideneguanosine hemihydrate (Gace). Experimental solid-state 1H NMR spectra obtained at 20 T using fast magic-angle spinning (MAS), here at 75 kHz, are presented for a dihydrate of G. For each guanosine derivative, the role of specific interactions is probed by means of NMR chemical shifts calculated using the density functional theory (DFT) gauge-including projector-augmented wave (GIPAW) approach for the full crystal and extracted isolated single molecules. Specifically, the isolated molecule to full crystal transformations result in net changes in the GIPAW calculated 1H NMR chemical shifts of up to 8 ppm for O–H···O, up to 6.5 ppm for N–H···N and up to 4.6 ppm for N–H···O hydrogen bonds; notably, the presence...

Molecular structure and spectral properties of ethyl 3-quinolinecarboxylate (E3Q) and [Ag(E3Q)2(TCA)] complex (TCA = Trichloroacetate)

A new [Ag(E3Q)2(TCA)] complex; (E3Q=Ethyl 3-quinolinecarboxylate and TCA=Trichloroacetate) has been synthesized and characterized using elemental analysis, FTIR, NMR and mass spectroscopy. The molecular geometry and spectroscopic properties of the complex as well as the free ligand have been calculated using the hybrid B3LYP method. The calculations predicted a distorted tetrahedral arrangement around Ag(I) ion. The vibrational spectra of the studied compounds have been assigned using potential energy distribution (PED). TD-DFT method was used to predict the electronic absorption spectra. The most intense absorption band showed a bathochromic shift and lowering of intensity in case of the complex (233.7nm, f=0.5604) compared to E3Q (λmax=228.0nm, f=0.9072). The calculated 1H NMR chemical shifts using GIAO method showed good correlations with the experimental data. The computed dipole moment, polarizability and HOMO–LUMO energy gap were used to predict the nonlinear optical (NLO) properties. It is found that Ag(I) enhances the NLO activity. The natural bond orbital (NBO) analyses were used to elucidate the intramolecular charge transfer interactions causing stabilization for the investigated systems.

Characterization of structure and 1H NMR of methyl viologen encapsulated noria and substituted noria hosts from density functional theory

Density functional theory has been employed to characterize electronic structure, molecular electrostatic potential and 1H NMR of waterwheel-like macrocyclic host noria and its methyl derivative. Molecular electrostatic potential topography analyses reveal that substitution of methyl groups at reactive hydroxyls of noria engender deeper minima near the portal and inside the cavity of host. The complexes between noria or Me-noria hosts and methyl viologen (MV2+) exhibit distinct binding patterns. The structure of MV2+@noria shows penetration of MV2+ inside the central hole of the host whereas Me-noria complex possesses one of the aromatic rings of MV2+ resides near the host portal. Calculated interaction energy for complexation of Me-noria turns out to be 239kJmol−1, which is ∼20 times larger than that for noria host. Calculated 1H NMR chemical shifts predict deshielding of guest protons encapsulated within the cavity of host in the MV2+@noria complex compared to the isolated guest. The protons near the host portal led to up-field signals in the spectra of MV2+@Me-noria. Host-guest binding pattern and 1H NMR for complexation of noria and its methyl derivative are compared with those observed in well-known macrocycles such as β-cyclodextrin, cucurbit[8]uril, calix[5]arene and pillar[5]arene hosts.

Hydrogen bond studies in substituted imino-acetaldehyde oxime

The intramolecular hydrogen bond, molecular structure and vibrational frequencies of imino-acetaldehyde oxime and its twelve derivatives have been investigated by means of density functional (DFT) method with 6-311++G∗∗ basis set. The nature of these interactions, known as resonance assisted hydrogen bonds, has been discussed. As a geometrical indicator of a local aromaticity, the geometry-based HOMA index has been applied. Additionally the linear correlation coefficients between substituent constants and selected parameters in R position have been calculated. The results show that the hydrogen bond strength is mainly governed by the resonance variations inside the chelate ring induced by the substituent groups. The topological properties of the electron density distributions for OH⋯N intramolecular bridges have been analyzed in terms of the Bader theory of atoms in molecules (AIMs). Furthermore, calculated 1H NMR chemical shifts (δH) correlate well with the hydrogen-bond distance as well as electron density at the bond and ring critical points in the molecular electron density topography. Finally, the natural population analysis method has been used to evaluate the hydrogen bonding interactions.

Synthesis, molecular structure and spectral analysis of ethyl 4-formyl-3,5-dimethyl-1H-pyrrole-2-carboxylate thiosemicarbazone: A combined DFT and AIM approach

A new ethyl 4-formyl-3,5-dimethyl-1H-pyrrole-2-carboxylate thiosemicarbazone (EFDMPCT) has been synthesized and characterized by elemental analysis and FT-IR, 1H NMR, UV–Visible, DART-mass spectroscopy. Quantum chemical calculations have been performed by DFT level of theory using B3LYP functional and 6-31G (d,p) as basis set. The calculated 1H NMR chemical shifts using gauge including atomic orbitals (GIAO) approach are in good agreement with the observed chemical shifts. The electronic transitions within molecule have been interpreted using the time dependent density functional theory (TD-DFT). The calculated and experimental wavenumbers analyses confirm the existence of dimer. Topological parameters electron density, Laplacian of electron density, kinetic electron energy density, potential electron density and the total electron energy density at the bond critical points (BCP) analyzed using ‘Atoms in Molecules’ AIM theory reveals intra and inter molecular hydrogen bonding other weaker interactions in detail. The calculated intermolecular hydrogen bond energy of dimer is −12.2176 kcal/mol using AIM calculation. The results of AIM ellipticity confirm the existence of resonance assisted hydrogen bonds in dimer. The calculated thermodynamic parameters show that reaction is exothermic and non-spontaneous at room temperature. The local reactivity descriptors find the reactive sites within molecules have been calculated.

Binding of viologen derivatives to cucurbit[8]uril

Molecular interactions between cucurbit[8]uril host and methyl -(MV2+), ethyl -(EV2+), propyl -(PV2+) and butyl -(BV2+) viologen have been analyzed employing the density functional theory. The complexation of viologen guests with CB[8] favors complete encapsulation of guest within host cavity over lateral interactions from host portals. The lowest energy complex reveals that both α- and methylene protons of alkyl substituent interact with hydrophilic exterior of CB[8] via hydrogen bond interactions. These host–guest interactions are analyzed using quantum theory of atoms in molecules. It has been shown that amongst viologen derivatives, methyl viologen binds strongly to CB[8] and strength of binding decreases steadily with increasing aliphatic chain length of the substituent. Normal vibration analyses reveal that CO stretching vibrations from CB[8] (1788cm−1) downshifts to 1754cm−1 when ureido oxygens interact with viologen guest. The CO vibrations from hydrogen bonded interactions (1754cm−1) and those from noninteracting ones (1792cm−1) engender distinct vibrations in the complex. The CN stretching vibration of viologen cation exhibits a blue shift of 22cm−1 on encapsulation within CB[8] cavity. The direction of frequency shift of CO and CN stretching vibrations has been explained by combining MED topography with difference electron density maps and further been supported by natural bond orbital analysis. Calculated 1H NMR chemical shifts predict that β-protons of bipyridinium moiety are shielded due to encapsulation within the host cavity unlike α- or methylene protons participating in CO⋯H interactions which exhibit deshielding. These inferences are in consonant with 1H NMR experiments.

Molecular electrostatic potentials in Cucurbit[ n]uril ( n = 13–16) hosts

Charge distribution and 1H NMR chemical shifts in different Cucurbit[ n]uril {CB[ n] ( n = 13–16)} conformers, generated by flipping methylene groups adjacent to glycouril units, have been obtained by employing the density functional theory. The lowest energy conformer of CB[ n] has been endowed with symmetric architecture of methylene groups which engender uniform cavity and yield shallow minima near carbonyl oxygen’s on the host portals along the series. The effective cavity diameter and cavity height from the molecular electrostatic potential topography reveal that cavity diameter of these hosts varies from 16.1 Å for CB[13] to 20.9 Å for CB[16]; the cavity height of these hosts turn out to be nearly constant and equals ∼8.6 Å. CB[ n] family of hosts exhibit three different types of proton signals in the NMR spectra which include: methylene protons directing outside and towards the cavity of the host are denoted by H1 and H3 whereas the methine protons pointing outside the cavity are labeled as H2. Calculated 1H NMR chemical shifts in CB[ n] hosts follow the order: H3 > H2 > H1 in the gas phase and with water as solvent in consonant with the experimental spectra of lower CB[ n] homologues (J. Kim, I. Jung, S. Kim, E. Lee, J. Kang, S. Sakamoto, K. Yamaguchi, K. Kim, J. Am. Chem. Soc. 122 (2000) 540).

Cis and trans conformations in 3-substituted thietane-1-oxide

For a series of 3-substituted-thietane-1-oxide (3-R-TOX) derivatives (R=chloro, methyl, ethyl, acetate, t-buthyl, phenyl and p-chlorophenyl), the cis⇔ trans isomerization reactions have been theoretically studied in the frame of molecular orbital theory. Optimized geometries have been obtained at HF/6-31G** level, whereas the energetics and thermodynamics were calculated with basis sets that include polarization, diffuse functions and electron correlation at the second-order Møller–Plesset perturbation theory. The size and nature of the substituent seems to exert no influence on the structure of the thietane-1-oxide ring. Gas phase thermodynamics predict the cis isomers to be the preferred structure in these compounds as a result of the H10⋯O9 non-bonded interaction. The exception to this trend are the chloro and acetate derivatives where a 14 and 46% of the trans isomer, respectively, is predicted. In CCl 4 solution, the isomerization reaction would take place in large extent. The calculated 1H-NMR chemical shifts correlate well with the experimental data and demonstrate that the β-protons (H10) are magnetically sensible enough to allow the cis and trans isomeric forms to be distinguished. The β-protons chemical shifts calculated in CCl 4 do not differ appreciably from the gas phase values. The 17O-NMR signals have also been derived and the potentiality of this nucleus to be used to assign the preferred geometry as well as to follow the isomerization reaction, in this kind of compounds is pointed out. The present work also indicates that the S O stretching mode can be used to assign either a cis or trans conformation in these species, though this vibrational mode is strongly coupled with some ring and H–C–H angle deformation modes.

Comparison of experimental and calculated 1H NMR chemical shifts of geometric photoisomers of azo dyes

Quantum chemical calculations based on Density Functional Theory have been used to predict 1H NMR chemical shifts of the cis and trans isomers of three model azo-dye compounds. Calculated absolute chemical shift values, and differences between isomers, were in good agreement with experimentally assigned 1H NMR data. Simulated NMR spectra based on calculated chemical shifts proved useful in identifying differences between predicted and experimental data. The technique could prove valuable in assisting assignment of NMR spectra of more complex dyes of commercial interest, and preliminary investigations on larger systems indicate this is feasible.

Theoretical Investigation of the Relationship between Proton NMR Chemical Shift and Hydrogen Bond Strength.

Hartree-Fock, Møller-Plesset, and DFT (BLYP, B3LYP) calculations have been carried out using the 6-31+G(d,p) basis set to study the relationship between calculated (1)H NMR chemical shifts and calculated hydrogen bond strengths in several model low-barrier hydrogen bond complexes. For both the formic acid-substituted formate anion and enol-substituted enolate anion model systems, we find an excellent linear correlation between calculated hydrogen bond strength and predicted (1)H NMR chemical shift, with an average slope of 1.5 kcal/mol per ppm chemical shift.

Hydrogen-bonded structure of water in crosslinked polymer gel as studied by 1H NMR chemical shift data

The structure of water in poly(methacrylic acid) (PMAA) gel as a function of the degree of crosslinking of the PMAA gel was investigated by experimentally observed and theoretically calculated 1H NMR chemical shifts. On the basis of these results, the hydrogen-bonded structure of water in the gel was elucidated.