Artemisinin and two of its derivatives, dihydroartemisinin and artesunate, which are front line drugs against malaria, were investigated using Raman optical activity (ROA) and vibrational circular dichroism (VCD) experiments, both...

Chiral organic fluorophores have significant promise in the development of efficient emitters of circularly polarized light. Herein we describe a helically chiral boron dipyrromethene (BODIPY) with a hitherto unreported N,N,O,C‐boron‐chelation motif, synthesised by means of a one‐pot boron metathesis, nucleophilic aromatic substitution (SNAr), Suzuki coupling, boron chelation, cascade reaction. Resolution of the racemic BODIPY (by preparative HPLC on a chiral stationary phase) allowed examination of the chiroptical properties of the resulting enantiomers (λmax(abs)=593 nm, λmax(em)=622 nm, ϵ=30 000 m−1 cm−1, φF=0.49, |glum|=3.7×10−3 (hexane)). This is the first example of circularly polarised emission from a non‐C2‐symmetric helically chiral N,N,O,C‐BODIPY and as such provides a valuable benchmark for future developments in this compound series.

Chirality plays a crucial role in drug discovery and development. As a result, a significant number of commercially available drugs are structurally dissymmetric and enantiomerically pure. The determination of the exact 3D structure of drug candidates is, consequently, of paramount importance for the pharmaceutical industry in different stages of the discovery pipeline. Traditionally the assignment of the absolute configuration of druggable molecules has been carried out by means of X-ray crystallography. Nevertheless, not all molecules are suitable for single-crystal growing. Additionally, valuable information about the conformational dynamics of drug candidates is lost in the solid state. As an alternative, vibrational optical activity (VOA) methods have emerged as powerful tools to assess the stereochemistry of drug molecules directly in solution. These methods include vibrational circular dichroism (VCD) and Raman optical activity (ROA). Despite their potential, VCD and ROA are still unheard of to many organic and medicinal chemists. Therefore, the present review aims at highlighting the recent use of VOA methods for the assignment of the absolute configuration of chiral small-molecule drugs, as well as for the structural analysis of biologics of pharmaceutical interest. A brief introduction on VCD and ROA theory and the best experimental practices for using these methods will be provided along with selected representative examples over the last five years. As VCD and ROA are commonly used in combination with quantum calculations, some guidelines will also be presented for the reliable simulation of chiroptical spectra. Special attention will be paid to the complementarity of VCD and ROA to unambiguously assess the stereochemical properties of pharmaceuticals.

Vibrational circular dichroism (VCD) and Raman optical activity (ROA) are two spectroscopic techniques that are sensitive towards the conformational behaviour of molecules, and are often complementary herein. In this work...

The transferrin proteins exhibit two high affinity Fe(III) binding pockets and are responsible for the iron transport into cells of higher order organisms. Previously, transferrins have been studied as possible transporter molecules for drugs delivery. In this study, Raman optical activity (ROA) was employed to investigate human serum transferrin. Due to the presence of Fe(III) in the holo form of the protein, it is in resonance with the the laser excitation wavelength (of 532 nm) used in the experiments. Consequently, resonance enhanced ROA bands were observed in the spectrum of the holo form. Nevertheless, far from resonance bands, arising from the protein backbone, could simultaneously be observed in the ROA spectrum of the holo form. This implies that ROA can be used to provide simultaneously information on the metal binding pocket as well as on the secondary structure of the protein. Furthermore, it was found that the amount of observed resonance enhanced ROA signals can be tuned by partially removing the iron present in the protein. Electronic circular dichroism (ECD) was employed to verify the Raman/ROA results.

The long-standing discussion of the absolute configuration of erythro-mefloquine is revisited, showcasing the strength of a combination of experimental and calculated vibrational circular dichroism spectroscopy.

Carbapenem resistance caused by metallo-β-lactamases is a serious global challenge that, if not tackled efficiently, is expected to lead to millions of deaths in the coming decades. Verona-integron encoded metallo-β-lactamase 2 (VIM-2) is a bacterial enzyme that has been reported from multidrug-resistant nosocomial isolates of Pseudomonas aeruginosa and other Gramnegative pathogens. As it hydrolyzes most β-lactams efficiently, including carbapenems, it is a major threat to current antimicrobial chemotherapies. So far, there is no clinically applicable inhibitor for this enzyme. In this work, the backbone NMR resonance assignment of VIM-2 is disclosed, opening up NMR investigations of this clinically important enzyme and its potential inhibitors for solutions, enabling a rational improvement of inhibitor candidates. Making use of the assignment, we identified the active enantiomer of a VIM-2 inhibitor candidate as well as its possible binding site and K d , utilizing NMR chemical shift titration experiments.

Five new compounds—rhodimer ( 1 ), rhodiflavan A ( 2 ), rhodiflavan B ( 3 ), rhodiflavan C ( 4 ), and rhodacarpin ( 5 )—along with 16 known secondary metabolites, were isolated from the CH 2 Cl 2 –CH 3 OH (1:1) extract of the roots of Tephrosia rhodesica . They were identified by NMR spectroscopic, mass spectrometric, X-ray crystallographic, and ECD spectroscopic analyses. The crude extract and the isolated compounds 2 – 5 , 9 , 15 , and 21 showed activity (100% at 10 μg and IC 50 = 5–15 μM) against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum .