Search Results (31)

The structure of N-[(2H-1,3-benzodioxol-5-yl)methyl]-2-(2,2,2-trichloroacetamido)benzamide was verified by using a combination of 1D and 2D NMR techniques. Fully assigned data from 1D NMR (¹H, ¹³C and DEPT 135) and 2D NMR (COSY, HMQC, HMBC) spectra was presented for the compound. The ¹H NMR spectrum of the ABX spin system in the benzodioxol moiety was simulated to predict the corresponding ⁿJ_HH coupling constants. The spectral assignments for the structure were supported by interpretive library search and HOSE predictions. Full article

This study investigates the influence of weak hydrogen bonds on the conformational properties and spectral characteristics of cannabidiol (CBD). Using a combination of FTIR and NMR spectroscopy, we analyze the effects of intramolecular hydrogen bonding, particularly the O-H∙∙∙π interactions, on the molecular behavior of CBD in chloroform solution. FTIR spectra reveal distinct ν_s(O-H) stretching bands at 3603 cm⁻¹ and 3425 cm⁻¹, corresponding to free and hydrogen-bonded -OH groups, respectively, with experimental results aligning closely with computational data for CBD conformers. Notably, conformer 1a predominates in solution, with weaker hydrogen bonding observed for the -OH(B) group compared to -OH(A). Additionally, the formation of -OH∙∙∙π hydrogen bonds affects key vibrational bands in the 1700–1300 cm⁻¹ region. NMR analysis shows significant shifts in proton and carbon signals, emphasizing the influence of hydrogen bonding on CBD’s electronic environment. The observed changes in coupling constants, although subtle, further highlight the impact of these interactions on spin–spin coupling. Overall, these findings provide deeper insights into the structural and electronic factors governing CBD’s behavior in solution, offering a basis for future studies on hydrogen bonding in biomolecules and their pharmacological implications. Full article

Cathinone and its synthetic derivatives belong to organic compounds with narcotic properties. Their structural diversity and massive illegal use create the need to develop new analytical methods for their identification in different matrices. NMR spectroscopy is one of the most versatile methods for identifying the structure of organic substances. However, its use could sometimes be very difficult and time-consuming due to the complexity of NMR spectra, as well as the technical limitations of measurements. In such cases, molecular modeling serves as a good supporting technique for interpreting ambiguous spectral data. Theoretical prediction of NMR spectra includes calculation of nuclear magnetic shieldings and sometimes also indirect spin–spin coupling constants (SSCC). The quality of theoretical prediction is strongly dependent on the choice of the theory level. In the current study, cathinone and its 12 fluorinated derivatives were selected for gauge-including atomic orbital (GIAO) NMR calculations using Hartree–Fock (HF) and 28 density functionals combined with 6-311++G** basis set to find the optimal level of theory for ¹H, ¹³C, and ¹⁹F chemical shifts modeling. All calculations were performed in the gas phase, and solutions were modeled with a polarized-continuum model (PCM) and solvation model based on density (SMD). The results were critically compared with available experimental data. Full article

Caffeine is an alkaloid with a purine structure and has been well known for centuries due to its presence in popular drinks—tea and coffee. However, the structural and spectroscopic parameters of this compound, as well as its chemical and biological activities, are still not fully known. In this study, for the first time, we report on the measured oxygen-17 NMR spectra of this stimulant. To support the assignment of our experimental NMR data, extensive quantum chemical calculations of NMR parameters, including nuclear magnetic shielding constants and indirect spin–spin coupling constants, were performed. In a theoretical study, using nine efficient density functionals (B3LYP, BLYP, BP86, CAM-B3LYP, LC-BLYP, M06, PBE0, TPSSh, wB97x), and in combination with a large and flexible correlation-consistent aug-cc-pVTZ basis set, the structure and NMR parameters were predicted for a free molecule of caffeine and in chloroform, DMSO and water. A polarized continuum model (PCM) was used to include a solvent effect. As a result, an optimal methodology was developed for predicting reliable NMR data, suitable for studies of known, as well as newly discovered, purines and similar alkaloids. The results of the current work could be used in future basic and applied studies, including NMR identification and intermolecular interactions of caffeine in various raw materials, like plants and food, as well as in the structural and spectroscopic characterization of new compounds with similar structures. Full article

The design and synthesis of analogs of natural products can be a valuable source of medicinal preparations for the pharmaceutical industry. In the present study, the structural elucidation of eleven derivatives of 2,4-dihalogeno substituted synthetic analogues of the natural compound carvacrol was carried out by means of NMR experiments, and of another thirteen by DFT calculations. By selective NOE experiments and the irradiation of CH signals of the isopropyl group, individual conformers were assigned as syn and anti. By comparing GIAO/B3LYP/6-311++G(d,p)-calculated and experimentally measured vicinal ³J_CH spin-spin constants, this assignment was confirmed. An unusual relationship is reported for proton-carbon vicinal couplings: ³J_CH (180°) < ³J_CH (0°). The conformational mobility of carvacrols was studied by 2D EXSY spectra. The application of homonuclear decoupling technique (HOBS) to these spectra simplifies the spectra, improves resolution without reducing the sensitivity, and allows a systematic examination of the rotational barrier of all compounds via their CH signals of the isopropyl group in a wider temperature interval. The rate constants of the isopropyl rotation between syn and anti conformers were determined and the corresponding energy barriers (14–17 kcal/mol) were calculated. DFT calculations of the energy barriers in carvacrol derivatives allowed the determination of the steric origin of the restricted isopropyl rotation. The barrier height depends on the size of the 2- and 4-position substituents, and is independent of the derivatization of the OH group. Full article

Tumor hypoxia plays an important role in the clinical management and treatment planning of various cancers. The use of 2-nitroimidazole-based radiopharmaceuticals has been the most successful for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging probes, offering noninvasive means to assess tumor hypoxia. In this study we performed detailed computational investigations of the most used compounds for PET imaging, focusing on those derived from 2-nitroimidazole: fluoromisonidazole (FMISO), fluoroazomycin arabinoside (FAZA), fluoroetanidazole (FETA), fluoroerythronitroimidazole (FETNIM) and 2-(2-nitroimidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5). Conformational analysis, structural parameters, vibrational IR and Raman properties (within both harmonic and anharmonic approximations), as well as the NMR shielding tensors and spin-spin coupling constants were obtained by density functional theory (DFT) calculations and then correlated with experimental findings, where available. Furthermore, time-dependent DFT computations reveal insight into the excited states of the compounds. Our results predict a significant change in the conformational landscape of most of the investigated compounds when transitioning from the gas phase to aqueous solution. According to computational data, the 2-nitroimidazole moiety determines to a large extent the spectroscopic properties of its derivatives. Due to the limited structural information available in the current literature for the investigated compounds, the findings presented herein deepen the current understanding of the electronic structures of these five radiopharmaceuticals. Full article

D-Glucuronic acid is a fundamental building block of many biologically important polysaccharides, either in its non-substituted form or bearing a variety of substituents, among them sulfates. We have previously performed a study of the effects of exhaustive sulfation on the conformational behavior of β-gluronopyranosides. Herein, we report an investigation comparing α- and β-derivatives of this monosaccharide within the title disaccharides using NMR and quantum chemistry approaches. It was found that for α-linked disaccharides, the introduction of sulfates did not greatly affect their conformational behavior. However, for β-derivatives, considerable conformational changes were observed. In general, they resemble those that took place for the monosaccharides, except that NOESY experiments and calculations of intra-ring spin–spin coupling constants suggest the presence of a ¹S₅ conformer along with ³S₁ in the fully sulfated disaccharide. During the synthesis of model compounds, hydrogen bond-mediated aglycone delivery was used as an α-directing stereocontrol approach in the glucuronidation reaction. Full article

We present new compact pecJ-n (n = 1, 2) basis sets for the selenium atom developed for the quantum–chemical calculations of NMR spin–spin coupling constants (SSCCs) involving selenium nuclei. These basis sets were obtained at the second order polarization propagator approximation with coupled cluster singles and doubles amplitudes (SOPPA(CCSD)) level with the property-energy consistent (PEC) method, which was introduced in our previous papers. The existing SSCC-oriented selenium basis sets are rather large in size, while the PEC method gives more compact basis sets that are capable of providing accuracy comparable to that reached using the property-oriented basis sets of larger sizes generated with a standard even-tempered technique. This is due to the fact that the PEC method is very different in its essence from the even-tempered approaches. It generates new exponents through the total optimization of angular spaces of trial basis sets with respect to the property under consideration and the total molecular energy. New basis sets were tested on the coupled cluster singles and doubles (CCSD) calculations of SSCCs involving selenium in the representative series of molecules, taking into account relativistic, solvent, and vibrational corrections. The comparison with the experiment showed that the accuracy of the results obtained with the pecJ-2 basis set is almost the same as that provided by a significantly larger basis set, aug-cc-pVTZ-J, while that achieved with a very compact pecJ-1 basis set is only slightly inferior to the accuracy provided by the former. Full article

In this work, 242 NMR spin–spin coupling constants (SSCC) in 20 molecules are calculated, either with correlated wave function methods, SOPPA and HRPA(D), or with density functional theory based on the B3LYP, BHandH, or PBE0 functionals. The calculations were carried out with and without treatment of solvation via a polarizable continuum model in both the geometry optimization step and/or the SSCC calculation, and thereby, four series of calculations were considered (the full-vacuum calculation, the full-solvent calculation, and the two cross combinations). The results were compared with experimental results measured in a solvent. With the goal of reproducing experimental values, we find that the performance of the PBE0 and BHandH SSCCs improves upon including solvation effects. On the other hand, the quality of the B3LYP SSCCs worsens with the inclusion of solvation. Solvation had almost no effect on the performance of the SOPPA and HRPA(D) calculations. We find that the PBE0-based calculations of the spin–spin coupling constants have the best agreement with the experimental data. Full article

The investigation of the sensitivity of the relativistic corrections to the NMR shielding constants (σ) to the configuration of angular spaces of the basis sets used on the atoms of interest was carried out within the four-component density functional theory (DFT). Both types of relativistic effects were considered, namely the so-called heavy atom on light atom and heavy atom on heavy atom effects, though the main attention was paid to the former. As a main result, it was found that the dependence of the relativistic corrections to σ of light nuclei (exemplified here by ¹H and ¹³C) located in close vicinity to a heavy atom (exemplified here by In, Sn, Sb, Te, and I) on the basis set used on the light spectator atom was very much in common with that of the Fermi-contact contribution to the corresponding nonrelativistic spin-spin coupling constant (J). In general, it has been shown that the nonrelativistic J-oriented and σ-oriented basis sets, artificially saturated in the tight s-region, provided much better accuracy than the standard nonrelativistic σ-oriented basis sets when calculating the relativistic corrections to the NMR shielding constants of light nuclei at the relativistic four-component level of the DFT theory. Full article

Attempts at the theoretical interpretation of NMR spectra have a very long and fascinating history. Present quantum chemical calculations of shielding and indirect spin-spin couplings permit modeling NMR spectra when small, isolated molecules are studied. Similar data are also available from NMR experiments if investigations are performed in the gas phase. An interesting set of molecules is formed when a methane molecule is sequentially substituted by fluorine atoms—CH_4-nF_n, where n = 0, 1, 2, 3, or 4. The small molecules contain up to three magnetic nuclei, each with a one-half spin number. The spectral parameters of CH_4-nF_n can be easily observed in the gas phase and calculated with high accuracy using the most advanced ab initio methods of quantum chemistry. However, the presence of fluorine atoms makes the calculations of shielding and spin-spin coupling constants extremely demanding. Appropriate experimental ¹⁹F NMR parameters are good but also require some further improvements. Therefore, there is a real need for the comparison of existing NMR measurements with available state-of-the-art theoretical results for a better understanding of actual limits in the determination of the best shielding and spin-spin coupling values, and CH_4-nF_n molecules are used here as the exceptionally important case. Full article

This review represents a compendium of computational studies of relativistic effects on the NMR chemical shifts of light nuclei caused by the presence of heavy main group p-block elements in molecules. The narration starts from a brief discussion of the relativistic theories and quantum chemical methods for the calculation of NMR chemical shifts at the relativistic level of the electronic theory. The main part of the review contains a survey on the relativistic calculations of NMR shielding constants of the most popular NMR-active light nuclei such as ¹H, ¹³C, ¹⁹F, ²⁹Si, ¹⁵N, and ³¹P of compounds containing heavy p-elements. A special focus is placed on the relativistic effects initiated by the 16th and 17th group elements. Different factors governing the behavior of the relativistic effects on the chemical shifts of light atoms are discussed. In particular, the stereochemistry of the relativistic “heavy atom on the light atom” effect and the influence of the spin–orbit relativistic effects on the vibrational contributions to the shielding constants of light nuclei are considered. Full article

The measurement of a time-varying magnetic field is different from a constant magnetic field, due to its field intensity variation with time. Usually, the time-varying magnetic field measurement converts the solution of the magnetic induction intensity into the calculation of the induced electromotive force (EMF); then, the magnetic induction intensity is obtained by the time integration of the EMF, but the process is vulnerable to external interference. In this paper, a non-steady state nuclear magnetic resonance (NSS-NMR) scheme for the measurement of a time-varying magnetic field is proposed. In a time-varying magnetic field environment, an RF excitation signal with a certain frequency bandwidth is applied to excite the nuclear spin system. The NSS-NMR signal, which varies with time in the frequency range corresponding to the frequency bandwidth of the RF excitation, could finally be obtained after a series of processing of the probe output signal. During the NSS-NMR experiment, an orthogonal dual-coil probe is adopted to synchronously generate the RF excitation and induce the probe output signal. Moreover, a directional coupler that utilized in the experiment outputs a reference signal from the coupling port for the subsequent signal processing. The experimental results show that the weak NSS-NMR signal is indeed observed. The longitudinal time-varying magnetic field ranges from 0.576 T to 0.582 T, which is inverted by the Larmor precession relationship, have been successfully detected based on the so-called NSS-NMR effect. Full article

In this paper, we presented new J-oriented basis sets, pecJ-n (n = 1, 2), for phosphorus and silicon, purposed for the high-quality correlated calculations of the NMR spin–spin coupling constants involving these nuclei. The pecJ-n basis sets were generated using the modified version of the property-energy consistent (PEC) method, which was introduced in our earlier paper. The modifications applied to the original PEC procedure increased the overall accuracy and robustness of the generated basis sets in relation to the diversity of electronic systems. Our new basis sets were successfully tested on a great number of spin–spin coupling constants, involving phosphorus or/and silicon, calculated within the SOPPA(CCSD) method. In general, it was found that our new pecJ-1 and pecJ-2 basis sets are very efficient, providing the overall accuracy that can be characterized by MAEs of about 3.80 and 1.98 Hz, respectively, against the benchmark data obtained with a large dyall.aae4z⁺ basis set of quadruple-ζ quality. Full article

Although 2-phosphonobutane-1,2,4,-tricarboxylic acid, PBTC, has manifold industrial applications, relevant and reliable data on the protonation of PBTC are poor. However, these data are critical parameters for ascertaining PBTC speciation, especially with regard to a sound structural and thermodynamic characterization of its metal ion complexes. A rigorous evaluation of pH-dependent ¹H, ¹³C, and ³¹P chemical shifts along with accessible scalar spin–spin coupling constants (J) was performed in order to determine the pK_a values of PBTC in 0.5 molal NaCl aqueous solution by means of nuclear magnetic resonance (NMR) spectroscopy. The phosphonate group revealed pK_a values of 0.90 ± 0.02 and 9.79 ± 0.02, and the pK_a values associated with the carboxylic groups are 3.92 ± 0.02, 4.76 ± 0.03, and 6.13 ± 0.03. Supported by DFT-calculated structures revealing strong intramolecular hydrogen bonding, the sequence of deprotonation could be unambiguously determined. Full article