GIAO/DFT studies on 1,2,4‐triazole‐5‐thiones and their propargyl derivatives

Density functional theory (DFT)/Becke–Lee–Yang–Parr (B3LYP) and gauge‐including atomic orbital (GIAO) calculations were performed on a number of 1,2,4‐triazole derivatives, and the optimized structural parameters were employed to ascertain the nature of their predominant tautomers. ¹³C and ¹⁵N NMR chemical shifts of 3‐substituted 1,2,4‐triazole‐5‐thiones and their propargylated derivatives were calculated via GIAO/DFT approach at the B3LYP level of theory with geometry optimization using a 6‐311++G** basis set. A good agreement between theoretical and experimental ¹³C and ¹⁵N NMR chemical shifts could be found for the systems investigated. The data generated were useful in predicting ¹⁵N chemical shifts of all the nitrogen atoms of the triazole ring, some of which could not be obtained in solution state ¹⁵N HMBC/HSQC NMR measurements. The energy profile computed for the dipropargylated derivatives was found to follow the product distribution profile of regioisomers formed during propargylation of 1,2,4‐triazole thiones. Copyright © 2013 John Wiley & Sons, Ltd.     

HMBC‐ und NOESY‐NMR‐Spektroskopie

In this article we first discuss the NMR pulse sequence HMBC (heteronuclear multiple bond correlation) and demonstrate its importance for the final structure verification of the natural product cytisine. The ¹H‐, ¹³C‐, COSY‐ und HSQC‐spectra of this compound have been shown in the first two articles of this series. After this we explain the physics of the NOESY‐experiment (nuclear Overhauser effect spectroscopy) and apply this for the stereochemical assignment of the proton signals. A correlation diagram between NOE integrals and hydrogen atom distances proofs the correct analysis.     

A Comparison between the Experimental and Theoretical Investigations on Carbon‐13 Isotropic Shielding Constants of Some Tripodal Tetraamine Ligands

The direct implementation of GIAO and CSGT methods for calculation of ¹³C isotropic shielding constants of fully protonated forms of six tripodal tetraamine ligands tren, pee, ppe, tpt, epb and ppb at the Hartree‐Fock level of theory are presented. The shielding constants were determined using hybrid methods (including a mixture of Hartree‐Fock exchange and DFT exchange‐correlation) and are close to the experimental data. A splayed‐like conformation was considered for fully protonated forms of all ligands, and it was confirmed that this is the most stable conformation for the latter form of such ligands. A good linear correlation between the calculated chemical shielding at gas‐phase and experimental shift values in D₂O solution was obtained.     

Ab Initio calculation of 19F NMR chemical shielding for alkaline‐earth‐metal fluorides

Gauge‐independent atomic orbital (GIAO) method at Hartree‐Fock (HF) and density functional theory (DFT) levels, respectively, was employed to calculate ¹⁹F NMR chemical shieldings of solid state alkaline‐earth‐metal fluorides MF₂ (M = Mg, Ca, Sr, Ba). The results show that, although the calculated ¹⁹F chemical shieldings tend to be larger than the experimental values, they have a fairly good linear relationship with the observed ones. The calculated results based on different combinations of basis sets show that the B3LYP (a hybrid of DFT with HF) predictions are greatly superior to the HF predictions. When a basis set of metal atom with effective core potential (ECP) has well representation of valence wavefunction, especially wavefunction of d component, and proper definition of core electron number, it can be applied to obtain ¹⁹F chemical shielding which is close to that of all‐electron calculation. The variation of ¹⁹F chemical shielding of alkaline‐earth‐metal fluorides correlates well with the lattice factor A/R².     

A Study of Transition‐Metal Organometallic Complexes Combining 35Cl Solid‐State NMR Spectroscopy and 35Cl NQR Spectroscopy and First‐Principles DFT Calculations

A series of transition‐metal organometallic complexes with commonly occurring metal? chlorine bonding motifs were characterized using ³⁵Cl solid‐state NMR (SSNMR) spectroscopy, ³⁵Cl nuclear quadrupole resonance (NQR) spectroscopy, and first‐principles density functional theory (DFT) calculations of NMR interaction tensors. Static ³⁵Cl ultra‐wideline NMR spectra were acquired in a piecewise manner at standard (9.4 T) and high (21.1 T) magnetic field strengths using the WURST‐QCPMG pulse sequence. The ³⁵Cl electric field gradient (EFG) and chemical shielding (CS) tensor parameters were readily extracted from analytical simulations of the spectra; in particular, the quadrupolar parameters are shown to be very sensitive to structural differences, and can easily differentiate between chlorine atoms in bridging and terminal bonding environments. ³⁵Cl NQR spectra were acquired for many of the complexes, which aided in resolving structurally similar, yet crystallographically distinct and magnetically inequivalent chlorine sites, and with the interpretation and assignment of ³⁵Cl SSNMR spectra. ³⁵Cl EFG tensors obtained from first‐principles DFT calculations are consistently in good agreement with experiment, highlighting the importance of using a combined approach of theoretical and experimental methods for structural characterization. Finally, a preliminary example of a ³⁵Cl SSNMR spectrum of a transition‐metal species (TiCl₄) diluted and supported on non‐porous silica is presented. The combination of ³⁵Cl SSNMR and ³⁵Cl NQR spectroscopy and DFT calculations is shown to be a promising and simple methodology for the characterization of all manner of chlorine‐containing transition‐metal complexes, in pure, impure bulk and supported forms.     

Complete assignments of 1H and 13C NMR resonances of oleanolic acid, 18α‐oleanolic acid,ursolic acid and their 11‐oxo derivatives

Complete assignments of ¹H and ¹³C NMR chemical shifts for oleanolic acid, 18α‐oleanolic acid, ursolic acid and their 11‐oxo derivatives based on ¹H, ¹³C, 2D DQF‐COSY, NOESY, HSQC, HMBC and HSQC‐TOCSY experiments were achieved. Copyright © 2003 John Wiley & Sons, Ltd.     

Structure determination of chamaedryosides A—C,three novel nor‐neo‐clerodane glucosides from Teucrium chamaedrys,by NMR spectroscopy

Three new nor‐neo‐clerodane diterpenes, named chamaedryoside A (1), B (2) and C (3), have been isolated from the organic extracts of Teucrium chamaedrys (L.) and their structural characterization has been accomplished by ¹H and ¹³C‐NMR spectra, and DEPT, by COSY, TOCSY, HSQC, HSQC‐TOSCY and HMBC experiments, as well as by ESI‐MS/MS techniques. The stereostructures have been elucidated by NOESY and computational calculations. Copyright © 2009 John Wiley & Sons, Ltd.     

Complete NMR assignment of 3, 4‐seco‐lup‐20(29)‐en‐3‐oic acid from Decatropis bicolor

Complete ¹H and ¹³C NMR chemical shift assignments for 3,4‐seco‐lup‐20(29)‐en‐3‐oic acid ( 1 ) have been established by means of two‐dimensional COSY, HSQC, HMBC and NOESY spectroscopic experiments as well as by analysis of MS data. Compound 1 was isolated from Decatropis bicolor (Zucc.) Radlk. (Rutaceae) in addition to six coumarins and one alkaloid of known structure. Copyright © 2012 John Wiley & Sons, Ltd.     

Molecular modeling for Cu(II)‐aminopolycarboxylate complexes: Structures,conformational energies,and ligand binding affinities

A ligand field molecular mechanics (LFMM) force field (FF) has been developed for d⁹ copper(II) complexes of aminopolycarboxylate ligands. Training data were derived from density functional theory (DFT) geometry optimizations of 14 complexes comprising potentially hexadentate N₂O₄, tetrasubstituted ethylenediamine (ed), and propylenediamine cores with various combinations of acetate and propionate side arms. The FF was validated against 13 experimental structures from X‐ray crystallography including hexadentate N₂O₄ donors where the nitrogens donors are forced to be cis and bis‐tridentate ONO ligands which generate complexes with trans nitrogen donors. Stochastic conformational searches for [Cu{ed(acetate)_n (propionate)_4‐n}]^2?, n = 0–4, were carried out and the lowest conformers for each system reoptimized with DFT. In each case, both DFT and LFMM predict the same lowest‐energy conformer and the structures and energies of the higher‐energy conformers are also in satisfactory agreement. The relative interaction energies for n = 0, 2, and 4 computed by molecular mechanics correlate with the experimental log β binding affinities. Adding in the predicted log β values for n = 1 and 3 suggest for this set of complexes a monotonic decrease in log β as the number of propionate arms increases. © 2013 Wiley Periodicals, Inc.     

1H, 13C, 17O NMR and quantum‐chemical study of the stereochemistry of the sulfoxide and sulfone derivatives of 3‐arylidene‐1‐thioflavan‐4‐one epoxides

The oxidation of the trans,cis‐( 2 ) and trans,trans‐epoxides ( 3 ) of differently substituted (Z)‐3‐arylidene‐1‐thioflavan‐4‐ones ( 1 ) with dimethyldioxirane (DMD) yielded the appropriate sulfoxides ( 4, 5 ) and sulfones ( 6, 7 ). The structures were elucidated by the extensive application of one‐ and two‐dimensional ¹H, ¹³C and ¹⁷O NMR spectroscopy. The conformational analysis was achieved by the application of ³J(C,H) coupling constants, NOESY responses and ab initio calculations. The preferred ground‐state conformers (twisted envelope‐A, twisted envelope‐B for 6 and twisted envelope‐A, envelope‐B for 7 ) were obtained as global minima of the theoretical ab initio MO study and also the examination of the ¹⁷O and ¹³C chemical shifts, calculated for the global minima structures of the sulfone isomers by the GIAO method. Analogous results, obtained for the sulfoxide isomers ( 4, 5 ), not only led to the preferred conformers but also gave evidence for the trans arrangement of the 2‐Ph group and the oxygen atom of the S?O group. Chemical shift differences between the isomers, sulfoxides and sulfones were corroborated by ab initio calculations of the anisotropic effects of the oxirane ring and the S?O and SO₂ groups. Copyright © 2003 John Wiley & Sons, Ltd.     

Calculations of solid‐state 43Ca NMR parameters: A comparison of periodic and cluster approaches and an evaluation of DFT functionals

We present a computational study of magnetic‐shielding and quadrupolar‐coupling tensors of ⁴³Ca sites in crystalline solids. A comparison between periodic and cluster‐based approaches for modeling solid‐state interactions demonstrates that cluster‐based approaches are suitable for predicting ⁴³Ca NMR parameters. Several model chemistries, including Hartree–Fock theory and 17 DFT approximations (SVWN, CA‐PZ, PBE, PBE0, PW91, B3PW91, rPBE, PBEsol, WC, PKZB, BMK, M06‐L, M06, M06‐2X, M06‐HF, TPSS, and TPSSh), are evaluated for the prediction of ⁴³Ca NMR parameters. Convergence of NMR parameters with respect to basis sets of the form cc‐pVXZ (X = D, T, Q) is also evaluated. All DFT methods lead to substantial, and frequently systematic, overestimations of experimental chemical shifts. Hartree–Fock calculations outperform all DFT methods for the prediction of ⁴³Ca chemical‐shift tensors. © 2017 Wiley Periodicals, Inc.     

Structure elucidation,complete NMR assignment and PM5 theoretical studies of new hydroxy‐aminoalkyl‐α,β‐unsaturated derivatives of the macrolide antibiotic josamycin

Four new hydroxy‐aminoalkyl derivatives of α,β‐unsaturated macrolide‐josamycin (2–5) have been synthesised and their structures have been studied by means of ¹H and ¹³C NMR and FT‐IR methods. Complete assignment of resonances in the ¹H and ¹³C NMR spectra has been made on the basis of ¹H? ¹³C HSQC, ¹H? ¹³C HMBC, ¹H? ¹H COSY, ¹H? ¹H NOESY 2D experiments. Spectroscopic data indicated that for the derivatives 3 and 4 some equilibrium between two different structures exists in contrast to derivatives 2 and 5. The lowest‐energy structures of the new derivatives of josamycin have been calculated and visualised by PM5 method at semi‐empirical level of theory, taking into account the NMR and FT‐IR data. The most significant differences between the structures of josamycin and its newly synthesised derivatives' were found in the conformation of the macrolide aglycone part and in the mutual orientation of the 4‐O‐isovalerylmycarosylmycaminose moiety relative to the aglycone part. PM5 semi‐empirical calculations indicated that the structures of the new macrolide derivatives are stabilised by rather weak intramolecular hydrogen bonds in agreement with spectroscopic data. Antimicrobial properties of the new derivatives 2–5 as well as those having an acetate group at C‐3 (6 and 7) were determined and compared to that of the parent macrolide antibiotic josamycin (1). Copyright © 2010 John Wiley & Sons, Ltd.     

Conformational Analysis and CD Calculations of Methyl‐Substituted 13‐Tridecano‐13‐lactones

Conformational models covering an energy range of 3 kcal/mol were calculated for (13S)‐tetradecano‐13‐lactone ( 3 ), (12S)‐12‐methyltridecano‐13‐lactone ( 4 ), and (12S,13R)‐12‐methyltetradecano‐13‐lactone ( 8 ), starting from a semiempirical Monte‐Carlo search with AM1 parametrization, and subsequent optimization of the 100 best conformers at the 6‐31G*/B3LYP and then the TZVP/B3LYP level of density‐functional theory. CD Spectra for these models were calculated by the time‐dependent DFT method with the same functional and basis sets as for the ground‐state calculations and Boltzmann weighting of the individual conformers. The good correlation of the calculated and experimental spectra substantiates the interpretation of these conformational models for the structure–odor correlation of musks. Furthermore, the application of the quadrant rule in the estimation of the Cotton effect for macrolide conformers is critically discussed.     

Solvent‐free microwave synthesis of bis‐pyrazolo[3,4‐b:4′,3′‐e]‐pyridines and study of their antifungal properties

The synthesis of a series of bis‐pyrazolo[3,4‐b:4′,3′‐e]pyridines ( 3 ) in the reaction of 5‐amino‐3‐methyl‐1‐phenylpyrazole ( 1 ) with aldehydes ( 2 ) under microwave irradiation and solvent‐free conditions is described. The structure elucidation of the products is based on detailed nmr analysis of experiments such as ¹H‐COSY, NOESY, DEPT, HSQC and HMBC. These compounds showed moderate antifungal in vitro activity against dermatophytes.     

The Studies of Structure of 2N‐(3‐phenyl‐allyl‐)(5‐phenyl‐[1,3,4] Thiadiazol‐2‐yl) Amine in Solution

2N‐(3‐phenyl‐allyl‐)(5‐phenyl‐[1,3,4] thiadiazol‐2‐yl) amine was studied by means of the ¹H, ¹³C, ¹⁵N NMR spectroscopy and DFT calculations. On the basis of the one‐dimensional ¹H, ¹³C, ¹⁵N‐NMR and two‐dimensional ¹H‐¹³C HMQC, ¹H‐¹³C HMBC, ¹H‐¹⁵N HMQC, ¹H¹H NOESY, ¹H¹H COSY correlation spectra the amine‐type and the imine‐type tautomers have been determined in the solution. Variety of structural forms including: biradical, ionic–biradical, and ionic structures of the amine‐type a and of the imine‐type b , c tautomers exist in the solution. According to the DFT computations the differences in the total energy between a and b , a and c , and b and c tautomers are equal to 1.5 kJ/mol, 1.2 kJ/mol, and 0.3 kJ/mol, respectively.     

Fully Automated Quantum‐Chemistry‐Based Computation of Spin–Spin‐Coupled Nuclear Magnetic Resonance Spectra

We present a composite procedure for the quantum‐chemical computation of spin–spin‐coupled ¹H NMR spectra for general, flexible molecules in solution that is based on four main steps, namely conformer/rotamer ensemble (CRE) generation by the fast tight‐binding method GFN‐xTB and a newly developed search algorithm, computation of the relative free energies and NMR parameters, and solving the spin Hamiltonian. In this way the NMR‐specific nuclear permutation problem is solved, and the correct spin symmetries are obtained. Energies, shielding constants, and spin–spin couplings are computed at state‐of‐the‐art DFT levels with continuum solvation. A few (in)organic and transition‐metal complexes are presented, and very good, unprecedented agreement between the theoretical and experimental spectra was achieved. The approach is routinely applicable to systems with up to 100–150 atoms and may open new avenues for the detailed (conformational) structure elucidation of, for example, natural products or drug molecules.     

DFT‐GIAO 1H and 13C NMR prediction of chemical shifts for the configurational assignment of 6β‐hydroxyhyoscyamine diastereoisomers

¹H and ¹³C NMR chemical shift calculations using the density functional theory–gauge including/invariant atomic orbitals (DFT–GIAO) approximation at the B3LYP/6‐311G++(d,p) level of theory have been used to assign both natural diastereoisomers of 6β‐hydroxyhyoscyamine. The theoretical chemical shifts of the ¹H and ¹³C atoms in both isomers were calculated using a previously determined conformational distribution, and the theoretical and experimental values were cross‐compared. For protons, the obtained average absolute differences and root mean square (rms) errors for each comparison showed that the experimental chemical shifts of dextrorotatory and levorotatory 6β‐hydroxyhyoscyamines correlated well with the theoretical values calculated for the (3R,6R,2′S) and (3S,6S,2′S) configurations, respectively, whereas for ¹³C atoms the calculations were unable to differentiate between isomers. The nature of the relatively large chemical shift differences observed in nuclei that share similar chemical environments between isomers was asserted from the same calculations. It is shown that the anisotropic effect of the phenyl group in the tropic ester moiety, positioned under the tropane ring, has a larger shielding effect over one ring side than over the other one. Copyright © 2009 John Wiley & Sons, Ltd.     

Torsion angle relationship of the 17O NMR chemical shift in α,β‐unsaturated carbonyl compounds

The torsion angle effect on the isotropic shielding of ¹⁷O nucleus in α,β‐unsaturated carbonyl groups is studied by means of density functional theory (DFT) calculations using a polarizable continuum model (PCM) for the solvent, employing the PBE0 functional together with the 6‐311G(d,p) basis set for geometry optimization, and the 6‐311+G(2d,p) basis set for calculating the NMR shielding with the gauge‐including atomic orbitals (GIAO) method. This study adds new information on the sensitivity of the ¹⁷O nucleus to conformational changes, revealing a strong dependence of the ¹⁷O NMR chemical shift on the dihedral angle between the carbonyl and the vinyl moiety in all studied compounds; remarkable differences are observed with the data reported for α‐diketones. Copyright © 2009 John Wiley & Sons, Ltd.     

Conformational Control of the Electronic Properties of an α‐β Terthiophene: Lessons from a Precursor Towards Dendritic Hyperbranched Oligo‐ and Poly‐Thiophenes

Herein we investigate the conformational and electronic properties of the 2,2′;3′,2“‐terthiophene ( B3T ) unit as the building block of thiophene dendrimeric materials. By means of DFT ground electronic state dihedral energy profiles, we get insight in the flexibility of B3 T as the prominent feature promoting the 3D arrangement. The presence of diverse conformers is explored by Raman and ¹H NMR spectroscopies. A theoretical estimation of the Raman and ¹H NMR spectra over the most energetically accessible conformers is found to be crucial for the appropriate assignment of the major conformer population derived from the experimental spectra. We show that energy barriers for the interconversion of conformers also play a role. Finally, the impact on the optical spectra (absorption and emission) of the α–α and α–β connections is studied and addressed by scanning the properties of the relevant low‐lying excited states. These studies highlight the relevance of the architecture of the basic molecular unit to understand charge and exciton behavior in organic semiconductors, particularly for those useful in photovoltaics.