Effects of different GIAO and CSGT models and basis sets on 2-aryl-1,3,4-oxadiazole derivatives

The direct molecular structure implementations of the gage-including atomic orbital (GIAO), individual gages for atoms in molecules (IGAIM) and continuous set of gage transformations (CSGT) methods for calculating nuclear magnetic shielding tensors at both the Hartree-Fock (HF) and density functional (B3LYP) levels of theory with 6-31G(d), 6-311G(d), 6-31++G(d,p), 6-311++G(d,p), and 6-311++G(df,pd) basis sets are presented. Dependence on the ¹H and ¹³C NMR chemical shifts on the choice of method and basis set have been investigated. Also, these chemical shifts of 2-aryl-1,3,4-oxadiazoles 5a–g have been performed related to dihedral angles (C4–C3–C2–O) of two conformers. The optimized molecular geometries and ¹H and ¹³C chemical shift values of 2-aryl-1,3,4-oxadiazoles 5a–g in the ground state have been obtained. The linear correlation coefficients of ¹³C NMR chemical shifts for these molecules were given. The new nuclear magnetic shielding tensors of tetramethylsilane (TMS) were calculated. The data of 2-aryl-1,3,4-oxadiazole derivatives display significant molecular structure and NMR analysis. Also, these provide the basis for future design of efficient materials having the 1,3,4-oxadiazole core.     

Experimental and ab initio theoretical vibrational Raman optical activity of tartaric acid

The vibrational Raman optical activity (ROA) spectra of (2R,3R)-(+) tartaric acid-d₀ in H₂O and (2R,3R)-(+) tartaric acid-d₄ in D₂O between 300 and 1800 cm⁻¹ measured in backscattering are reported. Ab initio Raman intensifies were evaluated using basis sets at 6-31G, 6-31G* and double zeta plus polarization (DZP) levels. Ab initio ROA intensities were obtained at two levels: in one calculation both the normal coordinates and the polarizability and optical activity tensor derivatives were evaluated with the 6-31G basis set; in a second calculation normal coordinates obtained with the DZP basis set were used to evaluate the normal coordinate derivatives of polarizability and optical activity tensors from the corresponding Cartesian derivative tensors obtained with the 6-31G basis set. Sufficiently good correlation was found between many of bands in the theoretical and experimental Raman and ROA spectra for both the -d₀ and -d₄ species to confirm that the absolute configuration of the ( + )-enantiomer is indeed (2R,3R) and to suggest that the trans COOH and trans COOD conformations are dominant. Tartaric acid-d₄ shows very similar ROA to tartaric acid itself in the range 300–800 cm⁻¹ but quite different in the range 800–1450 cm⁻¹, which provides insight into the influence of normal mode composition on ROA spectra. It was found that the normal mode compositions are much more sensitive to the level of basis set used than the polarizability and optical activity tensor derivatives.     

Simulation of 2D H homo- and H-C heteronuclear NMR spectra of organic molecules by DFT calculations of spin-spin coupling constants and H and C-chemical shifts

Simulation of 2D ¹H homo- and ¹H-¹³C heteronuclear NMR spectra of organic molecules are here suggested as a tool in the structure elucidation of organic compounds. DFT calculations of ¹H and ¹³C chemical shifts are performed on a sample compound, the ethyl ester of the exo-2-norbornanecarbamic acid, with the mPW1PW91 method using the 6-31G(d) basis set, following a full optimization of the geometry. Homo and heteronuclear spin-spin coupling constants are also calculated, providing full prediction of the common 2D ¹H-¹H COSY, 2D ¹H-¹³C HSQC, and 2D ¹H-¹³C HMBC.     

Sensitive monitoring of monoterpene metabolites in human urine using two-step derivatisation and positive chemical ionisation-tandem mass spectrometry

A gas chromatographic–positive chemical ionisation-tandem mass spectrometric (GC–PCI-MS/MS) method for the simultaneous determination of 10 oxidative metabolites of the monoterpenoid hydrocarbons α-pinene, (R)-limonene, and Δ³-carene ((+)-3-carene) in human urine was developed and tested for the monoterpene biomonitoring of the general population (n = 36). The method involves enzymatic cleavage of the glucuronides followed by solid-supported liquid–liquid extraction and derivatisation using a two-step reaction with N,O-bis(trimethylsilyl)-trifluoroacetamide and N-(trimethylsilyl)imidazole. The method proved to be both sensitive and reliable with detection limits ranging from 0.1 to 0.3 μg L⁻¹. In contrast to the frequent and distinct quantities of (1S,2S,4R)-limonene-1,2-diol, the (1R,2R,4R)-stereoisomer could not be detected. The expected metabolite of (+)-3-carene, 3-caren-10-ol was not detected in any of the samples. All other metabolites were detected in almost all urine samples.     

Quantum chemical studies on tautomerism of barbituric acid in gas phase and in solution

Ab initoand density functional theory (DFT) methods were used to study the tautomers of barbituric acid in the gas phase and in a polar medium. In the gas phase, the tautomers were optimized at the HF/6-31G^*, MP2/6-31G^*and B3LYP/6-31G^*, B3PW91/6-31G^*levels of theory. The self-consistent reaction field theory (SCRF) at the HF/6-31G^*level of theory has been used to optimize the tautomers in a polar medium. The relative stability of the tautomers was compared in the gaseous and polar mediums. The ability of maximum hardness principle to predict the stable tautomer has been studied. The ¹³C-NMR chemical shift for carbon atoms in the tautomers was calculated and the results are discussed.     

Preparation of the novel fluorine-18-labeled VIP analog for PET imaging studies using two different synthesis methods

Vasoactive intestinal peptide (VIP) receptors are expressed on various tumor cells in much higher density than somatostatin receptors, which provides the basis for radiolabeling VIP as tumor diagnostic agent. However, fast proteolytic degradation of VIP in vivo limits its clinical application. With the aim to develop and evaluate new ligands for depicting the VIP receptors with positron emission tomography (PET), the structure modified [R^8,15,21, L¹⁷]-VIP analog was radiolabeled with ¹⁸F using two different methods. With the first method, N-4-[¹⁸F]fluorobenzoyl-[R^8,15,21, L¹⁷]-VIP ([¹⁸F]FB-[R^8,15,21, L¹⁷]-VIP 7) was produced in a decay-corrected radiochemical yield (RCY) of 33.6 ± 3%, a specific radioactivity of 255 GBq/μmol (n = 5) within 100 min in four steps. Similarly, N-4-[¹⁸F](fluoromethyl)-benzoyl-[R^8,15,21, L¹⁷]-VIP ([¹⁸F]FMB-[R^8,15,21, L¹⁷]-VIP 8) was synthesized in a RCY of 34.85 ± 5%, a specific radioactivity of 180 GBq/μmol (n = 5) within 60 min in only one step. The two products 7 and 8 were both shown good stability in HSA. Moreover, the low bone uptakes of 7 and 8 in vivo of mice showed good defluorination stability.     

Introduction of a phosphorus ylide moiety into [η-(ω-hydroxy)alkenyl]chromium(0) carbene complexes with Ph3PCCO and consecutive Wittig alkenations with 2-alkynals. Part 12: the chemistry of metallacyclic alkenylcarbene complexes

Ketenylidenetriphenylphosphorane, Ph₃PCCO (2), reacts selectively with the ω-hydroxy group of the alkene-carbene complexes (OC)₄CrC(η²-NMeCH₂CHCHCH₂OH)R¹ (1) (R¹=Me: (1a); Ph: (1b)) to give the acyl ylide terminated complexes (OC)₄CrC[(4,5-η²)-NMeCH₂CHCHCH₂O(O)C-CHPPh₃]R¹ (3) (R¹=Me: (3a); Ph: (3b)). Complexes 3 undergo Wittig alkenation reactions with aldehydes such as 2-alkynals, R²-CC-CHO (R²=H, SiMe₃, Ph), to give the corresponding 4Z, 9E-dien-11-ynes (OC)₄CrC[(4,5-η²)-NMeCH₂CHCHCH₂O(O)C-CHCH-CC-R²]R¹ (4-6) (R¹=Me, R²=H, SiMe₃, Ph: (4a-6a); R¹=Ph, R²=H, SiMe₃, Ph: (4b-6b)). All complexes were characterized in solution by one- and two-dimensional NMR spectroscopy (¹H, ¹³C, ²⁹Si, ³¹P, ¹H/¹H COSY, ¹³C/¹H HETCOR, ³¹P/³¹P EXSY).     

Alnumycins A2 and A3: new inverse-epimeric pairs stereoisomeric to alnumycin A1

Two new pairs of stereoisomeric alnumycin As, A2 {(2)-(1R,1′RS,4′SR,5′SR)} and A3 {(2)-(1R,1′RS,4′SR,5′RS)}, are described. Similar to alnumycin A1 {(2)-(1R,1′RS,4′RS,5′SR)}, each of these naturally occurring compounds is also a pair of C-1 inverse epimers. The relative configurations of the dioxane ring sidechains were assigned on the basis of ¹H NMR NOE contacts and molecular modeling using density functional theory (DFT) at the M06-2X/6-31G(d) level of theory. The absolute configurations of C-1 and the determination of inverse epimeric relationships were achieved by experimental electronic circular dichroism (ECD) measurements, with both aspects confirmed by using the chiral derivatizing agent (CDA) Mosher′s acid chloride {α-methoxy-α-trifluorophenylacetyl chloride (MTPACl)} to effect enantiodifferentiation. The absolute configurations of the dioxane ring using the CDA could only be effected in the case of alnumycin A1, the results of which were in agreement with previous assignments. The dioxane ring conformational mobility and the likely interaction between the MTPA groups coupled with the structural novelty of the diols in the dioxane ring with respect to CDA analysis precluded an absolute configuration assignment for alnumycins A2 and A3 based on empirical comparisons or by computational analysis of through-space NMR shieldings (TSNMRS) emanating from the phenyl groups of the MTPA moieties.     

Asymmetric synthesis of passifloricin A: a correction in structure

The structure reported in the literature for the pharmacologically active, natural lactone passifloricin A (δ-lactone of 2Z,5R*S*,7R*,9S*,11S*-tetrahydroxyhexacos-2-enoic acid) is incorrect not only as regards stereochemical issues, but also in the placement of one of the hydroxyl groups of the side chain. By means of an unambiguous synthesis, passifloricin A is shown to be the δ-lactone of 2Z,5R,7S,9S,12S-tetrahydroxyhexacos-2-enoic acid. All of the stereogenic centres were created with the aid of Brown's asymmetric allylation methodology. The lactone ring was made via ring-closing metathesis.     

[1-B<Subscript>10</Subscript>H<Subscript>9</Subscript>N<Subscript>2</Subscript>]<Superscript>−</Superscript> and [1-CB<Subscript>9</Subscript>H<Subscript>10</Subscript>]<Superscript>−</Superscript> anions: an attempt of quantum chemical calculations

Comparative quantum chemical calculations of structural parameters, chemical shifts of ¹¹B NMR spectra, and atomic charges in 10-vertex boron hydride anions [1-CB₉H₁₀]⁻ and [1-B₁₀H₉N₂]⁻ were performed using the restricted Hartree-Fock method with the 6-31++G(D,P) basis set. Dedicated to Academician G. A. Abakumov on the occasion of his 70th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1853–1855, September, 2007.     

Si-NMR spectral assignments of polydisilahydrocarbons synthesised from diorganodichlorosilanes and styrene

In order to unambiguously assign the ²⁹Si-NMR chemical shifts of polydisilahydrocarbons containing structural units -CH₂Si¹(R₁R₂)Si²(R₁R₂)CHPh-, where R₁=R₂=Me or Ph, a model polymer viz., poly(tetramethyldisilyleneethylene) was synthesised through the dechlorination of 1,2-bis(chlorodimethylsilyl)ethane using potassium in toluene. The ²⁹Si-NMR spectrum of this polymer shows only one resonance peak at δ=−15.1 ppm due to Si atoms in the structural units, -CH₂Si(Me)₂Si(Me)₂CH₂- which unambiguously reveals that the chemical shift in the up field region of polydisilahydrocarbons containing structural units -CH₂Si¹(R₁R₂)Si²(R₁R₂)CH(Ph)- is due to Si¹, i.e., silicon attached to -CH₂- and accordingly, the chemical shift in the down field region is due to Si², i.e., silicon attached to -CH(Ph)-.     

NMR structure determination of (11E)-trinervita-1(14),2,11-triene, a new diterpene from sexual glands of termites

Female alates of Nasutitermes ephratae termites from Guadeloupe and Nasutitermes sp. from Brazil produce a diterpene hydrocarbon of the molecular formula C₂₀H₃₀ as the main component of their tergal gland secretion. Analysis of NMR, IR, and mass spectra of the diterpene led to a structure of (11E)-trinervita-1(14),2,11-triene. Based on a comparison with the published oxygenated trinervitane skeleton from termites we prefer the enantiomer with absolute configurations (4R,7S,8R,15S,16S). The suggested structure is supported by ab initio quantum chemical calculation of ¹H and ¹³C chemical shifts for the optimized geometry of the molecule.     

Crystal and molecular structure of 3-(2-amino-pyridinium)-propionate monohydrate

A novel betaine derivative, 3-(2-amino-pyridinium)-propionate monohydrate, has been synthesized and its structure studied by X-ray diffraction, FTIR, Raman, ¹H and ¹³C NMR spectroscopies and by DFT calculations. The crystals are monoclinic, space group P2₁/c with a=8.0800(16), b=15.242(3), c=7.1698(14) Å, β=104.30(3)° and Z=4. Each oxygen atom of the carboxylate group is engaged in two intermolecular hydrogen bonds, one with water molecule and the other with amine group. The water molecules link the molecules of 3-(2-amino-pyridinium)-propionate into planar zigzag chains along the b axis. The screening constants for ¹H and ¹³C atoms have been calculated by GIAO/B3LYP/6-31 G(d,p) and analyzed. Linear correlations between the experimental ¹H and ¹³C chemical shifts and the computed screening constants have been obtained. Raman and FTIR spectra of the title betaine have been investigated.     

Synthesis, molecular conformation, vibrational and electronic transition, isometric chemical shift, polarizability and hyperpolarizability analysis of 3-(4-methoxy-phenyl)-2-(4-nitro-phenyl)-acrylonitrile: a combined experimental and theoretical analysis

This work presents the synthesis and characterization of a novel compound, 3-(4-Methoxy-phenyl)-2-(4-nitro-phenyl)-acrylonitrile (abbreviated as 3-(4MP)-2-(4-NP)-AN, C₁₆H₁₂N₂O₃). The spectroscopic properties of the compound were examined by FT-IR, UV–vis and NMR (¹H and ¹³C) techniques. FT-IR spectrum in solid state was observed in the region 4000–400 cm⁻¹. The UV–vis absorption spectrum of the compound which dissolved in chloroform was recorded in the range of 200–800 nm. The ¹H and ¹³C NMR spectra were recorded in CDCl₃ solution. To determine lowest-energy molecular conformation of the title molecule, the selected torsion angle is varied every 10° and molecular energy profile is calculated from 0° to 360°. The structural and spectroscopic data of the molecule in the ground state were calculated using density functional theory (DFT) employing B3LYP/6-31G(d,p) basis set. The dipole moment, linear polarizability and first hyperpolarizability values were also computed using the same basis set. A study on the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. The HOMO and LUMO analysis were used to elucidate information regarding charge transfer within the molecule. The vibrational wavenumbers were calculated and scaled values were compared with experimental FT-IR spectrum. The complete assignments were performed on the basis of the experimental results and total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method. Isotropic chemical shifts were calculated using the gauge-invariant atomic orbital (GIAO) method. Comparison of the calculated frequencies, NMR chemical shifts, absorption wavelengths with the experimental values revealed that DFT and TD-DFT method produce good results. The linear polarizabilities and first hyperpolarizabilities of the studied molecule indicate that the title compound can be used as a good nonlinear optical material. The thermodynamic properties of the studied compound at different temperatures were calculated, revealing the correlations between standard heat capacity, standard entropy, standard enthalpy changes and temperatures.     

Structure,bioactivity and theoretical study of 1-cyano-<Emphasis Type="Italic">N</Emphasis>-p-tolylcyclo-propanecarboxamide

A novel cyclopropane derivative, 1-cyano-N-p-tolylcyclopropanecarboxamide (C₁₂H₁₂N₂O, Mr = 200.24) was synthesized and its structure was studied by X-ray diffraction, FTIR, ¹H and ¹³C NMR spectrum and MS. The crystals are monoclinic, space group P2_1/c with a = 7.109 (4), b = 13.758 (7), c = 11.505 (6) Å, α = 90.00, β = 102.731 (8), γ = 90.00 °, V = 1097.6 (9) ų, Z = 4, F(000) = 312, D _c  = 1.212 g/cm³, μ = 0.0800 mm^?1, the final R = 0.0490 and wR = 0.1480 for 1,375 observed reflections with I > 2σ(I). A total of 6,109 reflections were collected, of which 2,290 were independent (R _int = 0.0290). Theoretical calculation of the title compound was carried out with HF/6-31G (d,p), B3LYP/6-31G (d,p), MP2/6-31G (d,p). The full geometry optimization was carried out using 6-31G(d,p) basis set, and the frontier orbital energy. Atomic net charges were discussed, and the structure-activity relationship was also studied. The preliminary biological test showed that the synthesized compound is bioactive against the KARI of Escherichia coli.     

Theoretical binding affinities and spectra of complexes formed by a cyclic β-peptoid with amino acids

Binding affinities of a cyclic β-peptoid to amino acids were studied using the density functional theory (DFT) at the B3LYP/6-311G(d,p) level after the basis set superior error (BSSE). The host molecule possesses binding ability to amino acids since the binding energies of the complexes formed are negative. The complexes were stabilized via hydrogen bonds between the host and the guest molecules. Based on the B3LYP/6-31G(d) optimized geometries, electronic spectra of the complexes were calculated using the INDO/CIS method. ¹³C NMR spectra and nucleus-independent chemical shift (NICS) values of the complexes were computed at the B3LYP/6-31G(d) level. Carbon atoms in the carboxyl groups of the complexes are shifted downfield relative to those of the host. Some complexes exhibit aromaticity although the host shows anti-aromaticity. Formation of hydrogen bonds leads to cyclic current formation in these complexes.     

In Vitro 31P MR Chemical Shifts of In Vivo-Detectable Metabolites at 3T as a Basis Set for a Pilot Evaluation of Skeletal Muscle and Liver 31P Spectra with LCModel Software

Most in vivo ³¹P MR studies are realized on 3T MR systems that provide sufficient signal intensity for prominent phosphorus metabolites. The identification of these metabolites in the in vivo spectra is performed by comparing their chemical shifts with the chemical shifts measured in vitro on high-field NMR spectrometers. To approach in vivo conditions at 3T, a set of phantoms with defined metabolite solutions were measured in a 3T whole-body MR system at 7.0 and 7.5 pH, at 37 °C. A free induction decay (FID) sequence with and without ¹H decoupling was used. Chemical shifts were obtained of phosphoenolpyruvate (PEP), phosphatidylcholine (PtdC), phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), glycerophosphoetanolamine (GPE), uridine diphosphoglucose (UDPG), glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), 2,3-diphosphoglycerate (2,3-DPG), nicotinamide adenine dinucleotide (NADH and NAD⁺), phosphocreatine (PCr), adenosine triphosphate (ATP), adenosine diphosphate (ADP), and inorganic phosphate (Pi). The measured chemical shifts were used to construct a basis set of ³¹P MR spectra for the evaluation of ³¹P in vivo spectra of muscle and the liver using LCModel software (linear combination model). Prior knowledge was successfully employed in the analysis of previously acquired in vivo data.     

A concise methodology for the synthesis of (−)-Δ-tetrahydrocannabinol and (−)-Δ-tetrahydrocannabivarin metabolites and their regiospecifically deuterated analogs

The availability of tetrahydrocannabinols (Δ⁹-THC), tetrahydrocannabivarins (Δ⁹-THCV), and their metabolites in both their undeuterated and deuterated forms is critical for the analysis of biological and toxicological samples. We report here a concise methodology for the syntheses of (−)-Δ⁹-THC and (−)-Δ⁹-THCV metabolites in significantly improved overall yields using commercially available starting materials. Our approach allowed us to obtain the key intermediates (6aR,10aR)-9-nor-9-oxo-hexahydrocannabinols in four steps from (+)-(1R)-nopinone. This was followed by an optimized Shapiro reaction to give the (−)-11-nor-9-carboxy-metabolites, which were converted to their respective (−)-11-hydroxy analogs. The synthetic sequence involves a minimum number of steps, avoids undesirable oxidative conditions, and incorporates the costly deuterated resorcinols near the end of the synthetic sequence. This methodology enabled us to synthesize eight regiospecifically deuterated (−)-Δ⁹-THC and (−)-Δ⁹-THCV metabolites in a preparative scale and high optical purity without deuterium scrambling or loss.