NMR-Based Quantum Mechanical Analysis Builds Trust and Orthogonality in Structural Analysis: The Case of a Bisdesmosidic Triglycoside as Withania somnifera Aerial Parts Marker

Abstract

The present study demonstrates the relationship between conventional and quantum mechanical (QM) NMR spectroscopic analyses, shown here to assist in building a convincingly orthogonal platform for the solution and documentation of demanding structures. Kaempferol-3-O-robinoside-7-O-glucoside, a bisdesmosidic flavonol triglycoside and botanical marker for the aerial parts of Withania somnifera, served as an exemplary case. As demonstrated, QM-based 1H iterative full spin analysis (HiFSA) advances the understanding of both individual nuclear resonance spin patterns and the entire 1H NMR spectrum of a molecule and establishes structurally determinant, numerical HiFSA profiles. The combination of HiFSA with regular 1D 1H NMR spectra allows for simplified yet specific identification tests via comparison of high-quality experimental with QM-calculated spectra. HiFSA accounts for all features encountered in 1H NMR spectra: nonlinear high-order effects, complex multiplets, and their usually overlapped signals. As HiFSA replicates spectrum patterns from field-independent parameters with high accuracy, this methodology can be ported to low-field NMR instruments (40–100 MHz). With its reliance on experimental NMR evidence, the QM approach builds up confidence in structural characterization and potentially reduces identity analyses to simple 1D 1H NMR experiments. This approach may lead to efficient implementation of conclusive identification tests in pharmacopeial and regulatory analyses: from simple organics to complex natural products.

Computational simulation of 1H NMR profiles of complex biofluid analyte mixtures at differential operating frequencies: Applications to low‐field benchtop spectra

“…Further quantum mechanical‐based, field‐strength invariant analytical software options available include ChemAdder , which has been optimised as a superior tool for the preprocessing, interpretation, and provision of reliable quantitative NMR data from complex biofluid profile datasets, [ 60 ] and also Cosmic Truth (ct.nmrsolutions.io), a sophisticated example of its application being provided in Bhavaraju et al [ 61 ]…”

“…Further quantum mechanical-based, field-strength invariant analytical software options available ChemAdder, which has been optimised as a superior tool for the preprocessing, interpretation, and provision of reliable quantitative NMR data from complex biofluid profile datasets, [60] and also Cosmic Truth (ct.nmrsolutions.io), a sophisticated example of its application being provided in Bhavaraju et al [61] We have also demonstrated the applications of LF 60 MHz non-stationary 1 H NMR spectroscopy to the analysis of compositionally complex human biofluid samples, specifically human saliva in this case. Indeed, the detection and quantification of 5 salivary metabolites with more prominent, spectroscopically resolved 1 H NMR signals, that is, those of propionate, acetate, glycine, and methanol and its metabolite formate, was possible at an operating frequency of only 60 MHz.…”

Essential Terminology Connects NMR and qNMR Spectroscopy to Its Theoretical Foundation

“…For example, specific triglycosides of quercetin and kaempferol are important plant-organ specific quality markers of the medicinal plant, Ashwagandha (Withania somnifera). As the compounds contain robinose (α-L-Rha11→ 6 β-D-Gal) or rutinose (α-L-Rha11→ 6 β-D-Glc) and β-D-glucose, they give rise to many near-degenerate resonances, which can be fully understood by HiFSA [24] . While otherwise concealed by multiplet designation, the NMR spectra of these flavonoid glycosides contain highly structure-specific peak patterns with a myriad of underlying lines, all of which can be fully assigned to the individual H atoms.…”

“…While otherwise concealed by multiplet designation, the NMR spectra of these flavonoid glycosides contain highly structure-specific peak patterns with a myriad of underlying lines, all of which can be fully assigned to the individual H atoms. Importantly, the HiFSA-based understanding of the spectra allows the distinction and identification of close congeners, and even enables their analysis by benchtop NMR [24] . Also representing oligomers of congeneric building blocks, peptides are another class of higher molecular weight compounds that challenge HNMR spectroscopic data interpretation.…”

Combining NMR and MS to Describe Pyrrole-2-Carbaldehydes in Wheat Bran of Radiation

“…Computer-assisted spectral analysis exploits the underlying quantum mechanics to obtain complete structural information encoded in the NMR spectrum. A computational analysis for the full assignment of 1 H NMR spectra has been introduced under the term quantum-mechanical driven 1 H iterative full spin analysis (QM-HiFSA). − The basic systematic idea lies in total-line shape fitting iteration; spectral parameters are iteratively adjusted to minimize the difference in the pattern intensity between the observed and calculated spectra . NMR terminology as defined previously by Pauli et al (for the terms resonance, signal, pattern, peak, line, transition, split, multiplicity, and resolution) was used in this study…”