Electron capture dissociation of peptide hormone changes upon opening of the tocin ring and complexation with transition metal cations

Electron capture dissociation (ECD) is an analytical technique in mass spectrometry (MS) that allows detailed structural study of biomolecules to gain insight in their function. In this work the ECD behavior of two peptide hormones oxytocin (OT1) and vasopressin (VP1) was studied. The results of OT1 and VP1 were compared to structural analogues OT2 and VP2, which have similar amino acid sequences but lack the tocin ring. The ECD results showed that both the fragment type (c/z versus b/y) and the cleavage sites (ring versus tail) changed upon opening of the tocin ring. All four peptides were complexed with three different transition metal cations (Zn²⁺, Ni²⁺ and Cu²⁺) and the ECD results were compared to those obtained from the doubly protonated species. The use of various metal ions yielded different cleavages sites within the same peptide. This can be an effect of the metal ion itself, or a consequence of a change in conformation as was suggested earlier. In addition, the type of fragment ion varied for each metal‐complexed peptide, which is in agreement with previous observations. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis and structural aspects of N-triflylphosphoramides and their calcium salts--highly acidic and effective Brønsted acids

Recently, 1,1′‐bi‐2‐naphthol (BINOL)‐based N‐triflylphosphoramides emerged as a new class of potent Brønsted acid catalysts. In this paper we describe the efficient synthesis of various BINOL‐based N‐triflylphosphoramides and their calcium salts. Furthermore, X‐ray crystal structure analysis combined with energy‐dispersive X‐ray spectroscopy (EDX) measurements confirmed that the synthesised chiral N‐triflylphosphoramides are highly acidic metal‐free catalysts.     

Coordination of imidazoles by Cu(II) and Zn(II) as studied by NMR relaxometry, EPR, far-FTIR vibrational spectroscopy and ab initio calculations: effect of methyl substitution

Synthetic imidazole ligands are typically substituted at the N(1) ((1)-Im) position while natural imidazole ligands are substituted at the C(4) ((4)-Im) position. To outline the difference in coordination properties, the methyl-substituted imidazoles Me(4)-Im and Me(1)-Im were complexed with CuCl(2) and ZnCl(2) and investigated by NMR relaxometry, electron paramagnetic resonance, far-Fourier transform IR vibrational spectroscopy, and ab initio calculations. Me(4)-Im, Me(1)-Im, and Im in excess form the usual tetragonal D(4h) [CuL(4)X(2)] complexes with CuCl(2) whereas the methylated imidazoles form pseudotetrahedral C(2v) complexes instead of the usual octahedral O(h) [ZnIm(6)](2+) complex. All imidazoles display a high degree of covalence in the M-L σ- and π-bonds and the π-interaction strength affects the relative energies of complexation. Opportunities to tailor complexes by the chemical properties of the substituents are envisaged due to the role of the inductive and hyperconjugative effects, rather than position.     

Organoboron Reagent-Controlled Selective (Deutero)Hydrodefluorination

(Deuterium-labeled) CF₂H- and CFH₂-moieties are of high interest in drug discovery. The high demand for the incorporation of these fluoroalkyl moieties into molecular structures has witnessed significant synthetic progress, particularly in the (deutero)hydrodefluorination of CF₃-containing compounds. However, the controllable replacement of fluorine atoms while maintaining high chemoselectivity remains challenging. Herein, we describe the development of a selective (deutero)hydrodefluorination reaction via electrolysis. The reaction exhibits a remarkable chemoselectivity control, which is enabled by the addition of different organoboron sources. The procedure is operationally simple and scalable, and provides access in one step to high-value building blocks for application in medicinal chemistry. Furthermore, density functional theory (DFT) calculations have been carried out to investigate the reaction mechanism and to rationalize the chemoselectivity observed.     

Weighted proximity search

Journal of Heuristics - Proximity search is an iterative method to solve complex mathematical programming problems. At each iteration, the objective function of the problem at hand is replaced by...     

Chiral Brønsted acids in enantioselective carbonyl activations--activation modes and applications

Chiral phosphoric acids and derivatives have attracted considerable attention as a powerful tool in asymmetric catalysis. Various enantioselective reactions have been developed by using these efficient Br?nsted acid organocatalysts. Although initially the activation was restricted to reactive Br?nsted basic substrates, recent reports are demonstrating the versatility of phosphoric acid catalysts in the activation of carbonyl compounds in a stereochemically controlled fashion. This tutorial review gives an overview of enantioselective Br?nsted acid catalyzed transformations with the main focus on carbonyl activation. Different activation modes, key features of the catalysts and the applied substrates are presented and discussed with the goal to elucidate the origin of stereoselectivity in these Br?nsted acid catalyzed transformations.