Comparative study of the vibrational optical activity techniques in structure elucidation : the case of galantamine

The absolute configuration of the alkaloid galantamine was studied using a range of solution-state techniques; nuclear magnetic resonance (NMR), vibrational circular dichroism (VCD), and Raman optical activity (ROA). While the combined use of NMR and VCD does provide a fast, high-resolution methodology for determining the absolute configuration of galantamine, both techniques were needed in concert to achieve this goal. ROA, on the other hand, proved to be sensitive enough to assign the full absolute configuration without relying on other techniques. In both cases, statistical validation was applied to aid the determination of absolute configuration. In the case of galantamine, ROA combined with statistical validation is shown to be a powerful stand-alone tool for absolute configuration determination

Chiroptical studies on brevianamide B : vibrational and electronic circular dichroism confronted

Chiroptical spectroscopy, such as electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) are highly sensitive techniques to probe molecular conformation, configuration, solvation and aggregation. Here we report the application of these techniques to study the fungal metabolite brevianamide B. Comparison of the experimental ECD and VCD spectra with the density functional theory (DFT) simulated counterparts establishes that VCD is the more reliable technique to assign absolute configuration due to the larger functional and dispersion dependence of computed ECD spectra. Despite a low amount of available material, and a relatively unusual example of using VCD carbonyl multiplets, the absolute configuration could be reliably predicted, strengthening the case for application of VCD in the study of complex natural products. Spectral and crystallographic evidence for or against the formation of a dimeric aggregate is discussed; in solution the VCD spectra strongly suggest only monomeric species are present

Synthesis and Structural Diversification of Circularly Polarised Luminescence Active, Helically Chiral, “Confused” N,N,O,C‐BODIPYs**

Helically chiral boron-chelated dipyrromethene (BODIPY) dyes are known to exhibit solution phase circularly polarized luminescence (CPL), but examples are limited to a few synthetically accessible molecular architectures. We report a B−N chelation, SNAr, Suzuki cross-coupling, B−O chelation cascade reaction for the synthesis of understudied helically chiral, N,N,O,C-boron chelated, “confused” BODIPYs, from readily accessible 3,5-dibromo-BODIPY starting materials. Using this approach we have prepared a series of helically chiral “confused” BODIPYs with variation of the 3,5-subsitutents. Following resolution by chiral HPLC, absolute stereochemistry was assigned through comparison of the experimental and calculated ECD spectra, and solution phase chiroptical properties including CPL were determined (|glum| from 2.1 to 3.7×10−3; BCPL from 11.3 to 27.2)

Circularly polarized luminescence from helically chiral N,N,O,O-boron-chelated dipyrromethenes

Helically chiral N,N,O,O-boron chelated dipyrromethenes showed solution-phase circularly polarized luminescence (CPL) in the red region of the visible spectrum (λem(max) from 621 to 663 nm). The parent dipyrromethene is desymmetrised through O chelation of boron by the 3,5-ortho-phenolic substituents, inducing a helical chirality in the fluorophore. The combination of high luminescence dissymmetry factors (|glum| up to 4.7 ×10−3) and fluorescence quantum yields (ΦF up to 0.73) gave exceptionally efficient circularly polarized red emission from these simple small organic fluorophores, enabling future application in CPL-based bioimaging

Role of nitrogen lewis basicity in boronate affinity chromatography of nucleosides. Anal

Urinary modified nucleosides have a potential role as cancer biomarkers, and most of the methods used in their study have utilized low-pressure phenylboronate affinity chromatography materials for the purification of the cisdiol-containing nucleosides. In this study, a boronate HPLC column was surprisingly shown not to trap the nucleosides as would be expected from experience with the classic Affigel 601 resin but showed only partial selectivity toward cis-diol groups while other groups exhibited better retention. In aprotic conditions, trapping of nucleosides was possible; however, the selectivity toward cis-diol-containing compounds was lost with the Lewis basicity of available nitrogens being the main determinant of retention. The experimental findings are compared to and confirmed by DFT calculations. Modified nucleosides are naturally occurring modifications of the "normal" nucleosides. They have various roles within many nucleic acids but are mainly found in transfer RNA. They are excreted from the body via the urine as they cannot be salvaged; moreover, some are toxic when allowed to accumulate. Many past reports have investigated the modified nucleosides as potential cancer biomarkers and indicate considerable promise. [1][2][3][4][5] The methodologies used in these studies are wide ranging; however, since the introduction of boronate affinity chromatography as a ribonucleoside-selective cleanup step, on Affi-Gel 601 (Bio-Rad), utilized by Gehrke et al., 1,2 most research employed this off-line cleanup step process in the analysis. The subsequent identification/quantification of the ribonucleosides was almost exclusively carried out via RPLC-UV methods. More recently, some CE-UV methods have also been developed. [6][7][8][9] The further potential/ demand to obtain unambiguous identification via mass spectrometric detection led to the development of some off-line boronate chromatography GC/MS procedures. 3,5,10 However, the most natural choice for the analysis of the prepurified urinary nucleosides analysis is found in LC-MS. 11 Yet, the development of LC-MS procedures for urinary nucleosides only advanced 12 when electrospray mass spectrometry (ESI-MS) became available. Past studies by our group have considered the cleanup samples prior to ESI-MS analysis, 13 the optimization of the detection conditions, 14 comparison of various mass spectrometric methods, 15 and identification of the excreted nucleosides. 16,17 Other groups have taken advantage of mass spectrometry in the study of these compounds