Deuterium effects on the vibrational circular dichroism spectra of flavanone.

The minimum chemical modification that can be incorporated into an organic molecule is the replacement of a hydrogen atom for a deuterium atom. This change is not altering the pharmacological properties of a molecule, although it provides the possibility of making specific spectroscopic evaluations. Thus, in the present study, we explore how a stereogenic center is influenced by such an isotopic labeling. The studies were conducted on both enantiomers of flavanone (1 and 2) which is the parent molecule of a large group of pharmacologically active natural occurring secondary metabolites. Flavanone comprised 12 carbon atoms forming two benzene rings, a carbonyl group, an ethereal oxygen atom, a methylene group, and only one C-H stereogenic center, so it seems to be an ideal candidate for such studies. Density functional theory (DFT) calculations were used for the accurate prediction of vibrational circular dichroism (VCD) spectra of (R)-(3) and (S)-flavanone-2-d (4), of (R)-(5) and (S)-flavanone-3,3-d2 (6), and of (R)-(7) and (S)-flavanone-2',3',4',5',6'-d5 (8). To gain compounds that provide experimental VCD spectra for comparative purposes, the calculated spectra of both enantiomers of the corresponding flavanones, obtained after HPLC separation of the racemates by means of a chiral column, were contrasted, thereby revealing excellent agreements when using the CompareVOA software. In addition, the VCD spectra of both unlabeled enantiomeric flavanones (1 and 2) were also compared to the labeled molecules, revealing that the VCD spectra show significant variations induced by the deuterium incorporation.

Deuterated Curcuminoids: Synthesis, Structures, Computational/Docking and Comparative Cell Viability Assays against Colorectal Cancer.

A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring-deuterated hexamethoxy-CUR-BF2 and its corresponding CUR compound were also synthesized from a 2,4,6-trimethoxybenzaldehyde-3,5-d2 precursor. As with their protio analogues, the deuterated compounds were found to remain exclusively in the enolic form. The antiproliferative activities of these compounds were studied by in vitro bioassays against a panel of 60 cancer cell lines, and more specifically in human colorectal cancer (CRC) cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) and in normal colon cells (CCD841CoN). The deuterated CUR-BF2 adducts exhibited better overall growth inhibition by NCI-60 assay, while for other CUR-BF2 adducts the non-deuterated analogues were more cytotoxic. Results of the more focused comparative cell viability assays followed the same trend, but with some variation depending on cell lines. The CUR-BF2 adducts exhibited significantly higher cytotoxicity than CURs. Structural studies (X-ray and DFT) and computational molecular docking calculations comparing their inhibitory efficacy with those of known anticancer agents used in chemotherapy are also reported.

The utility of stable isotope labeled (SIL) analogues in the bioanalysis of endogenous compounds by LC-MS applied to the study of bile acids in a metabolomics assay.

The growing field of biomarker bioanalysis by liquid chromatography mass spectrometry (LC-MS) is challenged with the selection of suitable matrices to construct relevant and valid calibration curves resulting in not only precise but also accurate data. Because surrogate matrices are often employed with the associated concerns about the accuracy of the obtained data, here we present an assay using surrogate analytes in naive biological matrices. This approach is illustrated with the analysis of endogenous bile acids (e-BAs) in serum and plasma using stable isotope-labeled (SIL) analogues as calibration standards to address the matrix concerns. Several deuterated BAs (d-BAs) were used as standards representing respectively grouped e-BAs with structural similarity allowing for the simultaneous bioanalysis of 16 e-BA. The utility of this LC-MS assay employing d-BAs is demonstrated with the analysis of samples resultant of a controlled metabolomics study where a cohort of rats was fed/fasted to investigate the change of e-BAs dependent on food consumption and fasting time.

A new synthesis of brassinosteroids with a cholestane framework based on a highly functionalized starting material.

A new route to the synthesis of minor brassinosteroids with a cholestane framework (28-norcastasterone and 28-norbrassinolide) has been proposed. It makes use of commercially available 24-epicastasterone as a starting material. In addition, [26,26,26-(2)H3]-28-norcastasterone and [26,26,26-(2)H3]-28-norbrassinolide have been prepared as tools for analytical applications. The key steps were regioselective manipulations of functional groups in 24-epicastasterone, oxidative cleavage of 22,23-diol group and Claisen rearrangement.