Spin-spin Coupling Constants Research Articles

4hJCHOCH Spin Coupling in a Lewisx Trisaccharide as Evidence of Inter-Residue C-H···O Hydrogen Bonding in Aqueous Solution.

Prior studies of the solution conformation of the Lewisx (Lex) trisaccharide, αFuc-(1→3)[βGal-(1→4)]-βGlcNAc, suggest that nonclassical inter-residue C-H···O hydrogen bonding in aqueous solution contributes to the stabilization of its 3D structure and affects its biological properties. Experimental evidence for this hydrogen bond in aqueous solution has been reported in the form of a 4hJCHOCH NMR spin-coupling constant between C5'Fuc and H1″Gal measured by 2D NMR methods in unlabeled samples. A methyl glycoside of Lex (MeβLex) was prepared containing selective 13C-labeling at C5'Fuc, and the H1″Gal signal was examined in high-field 1H NMR spectra for evidence of splitting or line-broadening caused by the 13C at C5'Fuc. High-resolution 1H NMR spectra obtained at high field and at different temperatures using different FID processing parameters showed no resolved splitting of the H1″Gal signal or evidence of line-broadening. Spectral simulation showed that this splitting and/or line-broadening would be observable if the reported J-value (∼1.1 Hz) is correct. DFT calculations on MeβLex and a carbon analog (O5″Gal replaced by a CH2 group) gave very small and nearly identical calculated 4hJC5',H1″ values, suggesting that the coupling is essentially zero. DFT calculations also showed that an alternate inter-residue 3hJH5',H1″ is small. Based on NMR analyses and DFT calculations, we found that 4hJC5',H1″ in MeβLex has an upper limit of ∼0.4 Hz and that the value could be lower, possibly zero, calling into question its value as experimental proof of persistent nonclassical hydrogen bonding in aqueous solutions of MeβLex and related structures.

Probing the Electric Field Response of a Water Molecule Confined in Small Carbon Nanocages: A Density Functional Theory Investigation.

We consider a water molecule under tight confinement in the small-sized fullerenes (C28, C30, C32) within the density functional theory (DFT) calculations with suitable exchange-correlation functionals. Such nanoscopic molecular cages provide an ideal setup to study their characteristic properties not present in the condensed phase. The water molecule entirely loses its feature of typical water when it is confined in small fullerenes of size equal to C30or smaller, in which the asymmetric O-H stretching vibration occurs at a lower wavenumber than the symmetric stretching. We study the response of the confined water molecule to the applied electric fields in terms of change in geometrical parameters, NMR spin-spin coupling constants, dipole moment, HOMO-LUMO (HL) gap, and vibrational frequency shift. The electric field shielding property of small-sized fullerene cages is explored and found to be strongly correlated with the HL gap. Since the electric field modulates the gap to decrease generally, shielding efficiency varies with field strength, thereby making large fields better shielded than small fields for the small penetration factor at large fields. The results that hold significance for technological applications are discussed.

AIM/NBO Analysis of the Geminal Coupling Constants in the Stabilization of A-Type Dimeric Proanthocyanidin: Angular Dependence.

The angular dependence of the indirect short-range spin-spin coupling constants (SSCC), the geminal , , and in A-type dimeric proanthocyanidin, was investigated using density functional theory. We studied the rotation of ring B around the bond. Therefore, we calculated hyperconjugative charge transfers and bond polarizations within the natural bond orbital (NBO) approach, performing a topological study based on Bader's theory, AIM (atoms in molecules), and analyzing the angular dependence of AIM/NBO parameters. The results describe a relationship between the geminal coupling that changes with angular variation and NBO charge transfers to the bonds involved in the coupling pathways that can explain the behavior of the former property. Based on AIM/NBO data, inductive and mesomeric effects were described and quantified, showing a clear correlation with the stabilization of the structure, demonstrating a resonance-assisted inductive effect. We also set out strong hyperconjugative interactions (anomeric effect) involving nonbonding electron pairs of oxygen atoms. This analysis of coupling constants supports previous models by other authors and shows the application in this particular case. Moreover, the SSCCs studied herein are used for identifying stable structures and conformational search analysis of flavonoids. Finally, our results show the relationship between SSCCs and the structure stabilization and charge delocalization effects.

Caffeine-Legal Natural Stimulant with Open Research Perspective: Spectroscopic and Theoretical Characterization.

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.

Spin-Spin Coupling Constant Based on Reference Interaction Site Model Self-Consistent Field with Constrained Spatial Electron Density.

A method for computing spin-spin coupling constants (SSCCs) using the reference interaction site model self-consistent field with constrained spatial electron density (RISM-SCF-cSED) is proposed for the first time. Describing solvents using integral equation theory allows us to reflect solvent effects at atomic resolution in SSCCs while accounting for thermal fluctuations at a low computational cost. Applying the method to water, 1,1-difluoroethylene, and 1-methylaminomethylene-2-naphthalenone revealed that the solvent shift was evaluated to a greater extent than in the continuum solvent model. The origin of this phenomenon was analyzed in terms of the physical mechanisms underlying SSCCs.

Acetonyl C^N^N platinum(II) complexes of arylbipyridines.

This paper presents the first example of the formation of acetonyl tridentate CˆNˆN complexes of arylbipyridines in the reaction of chloroplatinum complexes with acetone in the presence of alkali. The chemical structure of obtained substances was established by means of 1H,13C NMR, COSY, HSQC, and HMBC techniques. The attribution of all proton and carbon signals in NMR spectra was performed using 1D and 2D NMR experiments for the synthesized acetonyl cycloplatinated complexes. A comparative analysis of the values of the C-Pt spin-spin coupling constants of the same order was carried out, which showed a significant difference in bond lengths and valence angles inthe cyclic fragments of the arylbipyridine ligand.

Analysis of <i>cis</i>-isomer-enriched dihydroquercetin sample by 1D and 2D NMR spectroscopy

Introduction. The structure of dihydroquercetin (DHQ) is characterized by two chiral centers at positions 2 and 3 of the benzopyran cycle, resulting in possible diastereomers: trans- and cis-isomers. Therefore, the development of methods for qualitative and quantitative control of DHQ diastereomers in analyzed samples is essential for patient safety management. Nuclear magnetic resonance (NMR) spectroscopy is one of the physicochemical methods that can be used for this purpose.Aim. The study objective was to accumulate the analytical and structural characteristics of cis-DHQ by NMR spectroscopy of the spheroidal form of this flavonoid (DHQs).Materials and Methods. 1D 1H, 1H,1H-COSY, 1H,1H-NOESY, and 1H,13C-HSQC NMR spectra were acquired at 298 K on an 800 MHz NMR spectrometer equipped with a TXI triple resonance probe. The number of scans was 32. The mixing time in the NOESY experiment was 400 ms. The 1H and 13C were analyzed using CcpNmr software. The dihedral angles were calculated by applying the Karplus equation.Results and discussion. In trans-DHQ, the chemical shift values for H2 and H3 are 4.93 ppm and 4.52 ppm, respectively, and in cis-DHQ they are 5.31 ppm and 4.20 ppm, respectively. The spin-spin coupling constants between H2 and H3 of trans- and cis-DHQ are 12.00 Hz and 2.40 Hz, respectively. Thus, the dihedral angles for the trans- and cis-isomers are 154° and 64°, respectively. We found that DHQs contains 12.5 % of the cis-isomer.Conclusion. Our experiments confirmed that NMR spectroscopy can discriminate between trans- and cis-DHQ based on the chemical shift values for the cross-peaks of H2 and H3. The second major finding was that this method can be considered as a more selective quantitative analysis than HPLC with UV detection without reference. One of the most important results of this study for drug development is the updated information on the structural parameters of DHQ diastereomers in the liquid phase.

Exploring Geometrical, Electronic and Spectroscopic Properties of 2-Nitroimidazole-Based Radiopharmaceuticals via Computational Chemistry Methods.

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.

Analyzing the photoassociation spectrum of ultracold 85Rb 133Cs molecule in (3)3Σ+ state.

We establish a theoretical model to analyze the photoassociative spectroscopy of 85Rb 133Cs molecules in the (3)3Σ+ state. The vibrational energy, spin-spin coupling constant, and hyperfine interaction constant of the (3)3Σ+ state are determined based on nine observed vibrational levels. Consequently, the Rydberg-Klein-Rees potential energy curve of the (3)3Σ+ state is obtained and compared with the ab initial potential energy curve. Our model can be adopted to analyze the photoassociative spectroscopy of other heteronuclear alkali-metal diatomic molecules in the (3)3Σ+ state.

On the performance of HRPA(D) for NMR spin–spin coupling constants: Smaller molecules, aromatic and fluoroaromatic compounds

In this study, the performance of the doubles-corrected higher random-phase approximation [HRPA(D)] has been investigated in calculations of nuclear magnetic resonance spin–spin coupling constants (SSCCs) for 58 molecules with the experimental values used as the reference values. HRPA(D) is an approximation to the second-order polarization propagator approximation (SOPPA) and is, therefore, computationally less expensive than SOPPA. HRPA(D) performs comparable and sometimes even better than SOPPA, and therefore, when calculating SSCCs, it should be considered as an alternative to SOPPA. Furthermore, it was investigated whether a coupled-cluster singles, doubles and perturbative triples [CCSD(T)] or Møller-Plesset second order (MP2) geometry optimization was optimal for a SOPPA and a HRPA(D) SSCC calculation for eight smaller molecules. CCSD(T) is the optimal geometry optimization for the SOPPA calculation, and MP2 was optimal for HRPA(D) SSCC calculations.

Exploring Alternate Methods for the Calculation of High-Level Vibrational Corrections of NMR Spin-Spin Coupling Constants.

Traditional nuclear magnetic resonance (NMR) calculations typically treat systems with a Born-Oppenheimer-derived electronic wave function that is solved for a fixed nuclear geometry. One can numerically account for this neglected nuclear motion by averaging over property values for all nuclear geometries with a vibrational wave function and adding this expectation value as a correction to an equilibrium geometry property value. Presented are benchmark coupled-cluster singles and doubles (CCSD) vibrational corrections to spin-spin coupling constants (SSCCs) computed at the level of vibrational second-order perturbation theory (VPT2) using the vibrational averaging driver of the CFOUR program. As CCSD calculations of vibrational corrections are very costly, cheaper electronic structure methods are explored via a newly developed Python vibrational averaging program within the Dalton Project. Namely, results obtained with the second-order polarization propagator approximation (SOPPA) and density functional theory (DFT) with the B3LYP and PBE0 exchange-correlation functionals are compared to the benchmark CCSD//CCSD(T) and experimental values. CCSD//CCSD(T) corrections are also combined with literature CC3 equilibrium geometry values to form the highest-order vibrationally corrected values available (i.e., CC3//CCSD(T) + CCSD//CCSD(T)). CCSD//CCSD(T) statistics showed favorable statistics in comparison to experimental values, albeit at an unfavorably high computational cost. A cheaper CCSD//CCSD(T) + B3LYP method showed quite similar mean absolute deviation (MAD) values as CCSD//CCSD(T), concluding that CCSD//CCSD(T) + B3LYP is optimal in terms of cost and accuracy. With reference to experimental values, a vibrational correction was not worth the cost for all of the other methods tested. Finally, deviation statistics showed that CC3//CCSD(T) + CCSD//CCSD(T) vibrational-corrected equilibrium values deteriorated in comparison to CCSD//CCSD(T) attributed to the use of a smaller basis set or lack of solvation effects for the CC3 equilibrium calculations.

Polar covalent apex-base bonding in borapyramidanes probed by solid-state NMR and DFT calculations.

Pyramidane molecules have attracted chemists for many decades due to their regular shape, high symmetry and their correspondence in the macroscopic world. Recently, experimental access to a number of examples has been reported, in particular the rarely reported square pyramidal bora[4]pyramidanes. To describe the bonding situation of the nonclassical structure of pyramidanes, we present solid-state Nuclear Magnetic Resonance (NMR) as a versatile tool for deciphering such bonding properties for three now accessible bora[4]pyramidane and dibora[5]pyramidane molecules. 11 B solid-state NMR spectra indicate that the apical boron nuclei in these compounds are strongly shielded (around -50 ppm vs. BF3 -Et2 O complex) and possess quadrupolar coupling constants of less than 0.9 MHz pointing to a rather high local symmetry. 13 C-11 B spin-spin coupling constants have been explored as a measure of the bond covalency in the borapyramidanes. While the carbon-boron bond to the -B(C6 F5 )2 substituents of the base serves as an example for a classical covalent 2-center-2-electron (2c-2e) sp2 -carbon-sp2 -boron σ-bond with 1 J(13 C-11 B) coupling constants in the order of 75 Hz, those of the boron(apical)-carbon(basal) bonds in the pyramid are too small to measure. These results suggest that these bonds have a strongly ionic character, which is also supported by quantum-chemical calculations.

NMR detection of the strained metallacycles in organolithiums: theoretical study.

For the first time through quantum chemistry methods, the effective use of 1JCLi spin-spin coupling constants as descriptors for assessing the formation of strained metallacycles is demonstrated. Both acyclic organolithiums and 3- to 7-membered metallacycles are examined. 80 organolithium compounds, including both monomeric and dimeric species, with ligands containing fluorine, nitrogen, oxygen, and carbon (in the form of carbanions), are tested. In general, the 1JCLi values below 12 Hz for monomeric species and below 6 Hz for dimeric species serve as clear indicators of strained monomeric metallacycle formation (for 6Li nuclei). The primary contributor to the overall 1JCLi value is the Fermi-contact term, which correlates directly with the carbon-lithium interatomic distance and allows to distinguish between dimers and monomers.

MA'AT analysis of the O-glycosidic linkages of oligosaccharides using nonconventional NMR J-couplings: MA'AT and MD models of phi.

MA'AT analysis (Meredith et al., J. Chem. Inf. Model. 2022, 62, 3135-3141) is a new NMR-based method to treat ensembles of redundant NMR spin-coupling constants (J-couplings) to obtain experiment-based probability distributions of molecular torsion angles in solution. Work reported to date on modeling the conformations of O-glycosidic linkages of oligosaccharides using three conventional J-coupling constraints (2 J COC, 3 J COCH, 3 J COCC) has shown that the method gives mean torsion angles and circular standard deviations (CSDs) for psi in very good agreement with those obtained by MD simulation. On the other hand, CSDs for phi determined by MA'AT analysis have consistently been much larger than those determined by MD, calling into question either the reliability of MA'AT analysis or MD to accurately predict this behavior. Prior work has shown that this discrepancy does not stem from the limitations of DFT-based J-coupling equation parameterization where secondary conformational dependencies can introduce uncertainties. The present work re-visits this problem by incorporating a new nonconventional J-coupling constraint into MA'AT analyses of phi, namely, a geminal (two-bond) 2 J CCH J-value that exhibits a strong primary dependence on phi. The latter property pertains explicitly to linkages contributed by GlcNAc pyranosyl rings and pyranosyl rings devoid of substituents at C2 (i.e., deoxy residues) where known secondary contributions to 2 J CCH magnitude caused by C-O bond rotation involving the coupled carbon are negligible or absent. The results show that when 2 J CCH values are added to the analysis, phi CSDs reduce considerably, bringing them into better alignment with those obtained by MD simulation. The cause of the discrepancy when only three conventional J-couplings are used to treat phi appears to be associated with the two-bond 2 J COC, which has properties that make it less effective than the non-conventional 2 J CCH as a discriminator of different conformational models of phi.

Structural determination of an isolated vasodilatory molecule from Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae)

The determination of the chemical structure of an isolated vasodilatory molecule from Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) was undertaken. This molecule was isolated from n-butanolic extract using bioassay-guided isolation with preparative plate chromatographic techniques and its structure was determined using spectroscopy (UV, 1D- and 2D NMR, MS). The vasodilatory activity of the isolate was investigated on guinea pig isolated aorta. The results show 3 spots from n-butanolic extract with respective retention factor (Rf) of 0.14, 0.6 and 0.91. Pharmacological investigations showed that the isolated molecule with Rf 0.91 relaxes the isolated aorta pre-contracted by norepinephrine. Data from chemical shifts (δH) and spin-spin coupling constants (JHH) were compared with literature to confirm the isolate as rutin. This is the first report of rutin isolated from Ludwigia octovalvis.

Stereocontrolled Synthesis and Conformational Analysis of a Series of Disaccharides α,β-d-GlcA-(1→3)-α-L-Fuc.

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.

Spin state and magnetic coupling in polynuclear Ni(II) complexes from density functional theory: is there an optimal amount of Fock exchange?

Reliable prediction of the ground-state spin and magnetic coupling constants in transition-metal complexes is a well-known challenge for density functional theory (DFT). One popular strategy for addressing this long-standing issue involves the modification of the fraction of Fock exchange in a hybrid functional. Here we explore the viability of this approach using three polynuclear metal-organic complexes based on a Ni4O4 cubane motif, having different ground state spin values (S = 0, 2, 4) owing to the use of different ligands. We systematically search for an optimum fraction of Fock exchange, across various global, range-separated, and double hybrid functionals. We find that for all functionals tested, at best there only exists a very narrow range of Fock exchange fractions which results in a correct prediction of the ground-state spin for all three complexes. The useful range is functional dependent, but general trends can be identified. Typically, at least two similar systems must be used in order to determine both an upper and lower limit of the optimal range. This is likely owing to conflicting demands of minimizing delocalization errors, which typically requires a higher percentage of Fock exchange, and addressing static correlation, which typically requires a lower one. Furthermore, we find that within the optimal range of Fock exchange, the signand relative magnitude of Ni-Ni magnetic coupling constants are reasonably well reproduced, but there is still room for quantitative improvement in the prediction. Thus, the prediction of spin state and magnetic coupling in polynuclear complexes remains an ongoing challenge for DFT.

Revisiting the influence of pH on 1JCαH and chemical shifts of glycine and alanine short oligopeptides.

The pH dependence of several NMR parameters of glycine and alanine short oligopeptides has been reported previously in different studies. Here we have thoroughly examined, summarized and demonstrated the dependences of 1H, 13C and 15N chemical shifts and protonation states of amino acids using two-dimensional NMR experiments. Nevertheless, 1JCαH one bond spin-spin coupling constants are more informative and convenient for determination of the position and protonation state of glycine and alanine residue in the oligopeptide chain. In particular, for various oligopeptides (up to six residues), it was shown that the pH dependence of 1JCαH of N-terminal glycine and alanine residues is larger than that of C-terminal groups, and in backbone residues, it is not influenced by pH and only slightly depends on the position of the amino acid residue in the chain.

The Triterpenoids from Munronia pinnata and Their Anti-Proliferative Effects.

Six new tirucallane-type triterpenoids, named munropenes A-F (1-6), were extracted from the whole plants of Munronia pinnata using a water extraction method. Their chemical structures were determined based on detailed spectroscopic data. The relative configurations of the acyclic structures at C-17 of munropenes A-F (1-6) were established using carbon-proton spin-coupling constants (2,3JC,H) and inter-proton spin-coupling constants (3JH,H). Furthermore, the absolute configurations of munropenes A-F (1-6) were determined through high-performance liquid chromatography (HPLC), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) analyses. The antiproliferative effects of munropenes A-F were evaluated in five tumor cell lines: HCT116, A549, HepG2, MCF7, and MDAMB. Munropenes A, B, D, and F (1, 2, 4, and 6) inhibited proliferation in the HCT116 cell line with IC50 values of 40.90, 19.13, 17.66, and 32.62 µM, respectively.

Boerelasins A-D, Four Unprecedented Cytochalasins from the Endophytic Fungus Boeremia Exigua.

Four undescribed cytochalasins (1-4) were isolated from the endophytic fungus Boeremia exigua. Structurally, boerelasin A (1) represents the first example of a cytochalasin with a rare 5/5 bicyclic carbon core. Boerelasin B (2) possesses an unprecedented 5/6/5/6/8 pentacyclic ring system. Boerelasin C (3), a derivative from the common biosynthetic intermediate to 1, is a macrocyclic ring-opening cytochalasin, and boerelasin D (4) contains an uncommon six-carbon alkyl acid side chain. The structures were elucidated based on spectroscopic methods, electronic circular dichroism, spin-spin coupling constants, and calculated nuclear magnetic resonance with DP4+ analysis. These compounds exhibited significant cytotoxicity against the tumor cells.