Formation Of Non-covalent Dimers Research Articles

A combined experimental and theoretical study of covalent vs noncovalent dimer formation in vanadium(V) complexes with Schiff base ligands

This manuscript reports the synthesis, spectroscopic and X-ray characterization of three new vanadium(V) complexes, namely [VO2L1] (1), (μ-O)2[V(O)(L2)2]·2CH3CN (2) and (μ-O)2[V(O)(L3)2]·CH3CN (3) [HL1 (2-ethoxy-6-((quinolin-8-ylimino)methyl)phenol), HL2 (2-(1-(2-(methylamino)ethylimino)propyl)phenol) and HL3 (2-(1-(2-(ethylamino)ethylimino)propyl)phenol)]. Complex 1 is a mononuclear dioxovanadium(V) system containing a five coordinated metal center, whilst complexes 2 and 3 are centrosymmetric dinuclear systems with two [(L)V = O] moieties [(L2)- for 2 and (L3)- for 3], which are linked together through asymmetrically bridging oxygen atoms. DFT calculations have been used to rationalize the different behavior of complex 1, that is related to the lack of strong H-bond donors and strong ability to self-assemble via electrostatically enhanced π-stacking interactions. Moreover, the strength of π–π and CH–π interactions has been evaluated and the interactions have been characterized by several computational tools like MEP, QTAIM and NCI Plot.

Effect of Self-Association on the Phase Stability of Triphenylamine Derivatives.

The self-association equilibrium, i.e. formation of noncovalent dimers, in two triphenylamine derivatives, TPD (N,N'-bis(3-methylphenyl)-N,N'-diphenylbenzidine) and mMTDAB (1,3,5-tris[(3-methylphenyl)phenylamino]benzene), in solution was evaluated by (1)H NMR spectroscopy. The gas-phase energetics of the respective dimerization processes was explored by computational quantum chemistry. The results indicate that self-association is significantly more extensive in TPB than in TDAB. It is proposed that this fact helps to explain why TPB presents a stability higher than expected in the liquid phase, which is reflected in a lower melting temperature, a less volatile liquid, and possibly a higher tendency to form a glass. These results highlight the influence of self-association on the phase equilibria and thermodynamic properties of pure organic substances.

Biosynthetic engineered B28K–B29P human insulin monomer structure in water and in water/acetonitrile solutions

Insulin engineering is a process intended to obtain desired therapeutic properties by rationally designed sequence mutations of a wild type insulin (HI) which originally consists of two chains, having 21 and 30 amino acids (AA) in chain A and B, respectively, held together by two disulfide bridges, namely A7–B7 and A20–B19 and intra strand bridge in chain A; A6–A11. It is known that human insulin (HI) circulates in the bloodstream as a monomer and in such a form passes effectively through the capillary membrane and binds to the insulin receptor (DeFelippis et al. 2001). An increase in insulin concentration causes formation of noncovalent dimers and higher oligomers. These entities are present in pharmaceutical preparations. Natural propensity of insulin to self-association has meaningful implication on pharmacokinetic behaviour upon hormone administration. Insulin diffusion into tissues entails progressive dissociation of hexamers into dimers and monomers. This is revealed as an increase in a serum insulin concentration reaching a maximum at approximately 2–3 h after subcutaneous injection and followed by slow regression within 9 h. Such pharmacokinetic behaviour causes inconvenience to patients forcing them to adapt their schedules to a medicine, what adversely affects their quality of life. Therefore, two therapeutic strategies have emerged with the potential to mimic physiological insulin secretion. First, rapid-acting insulin analogues were designed to have a more rapid onset of action than HI preparations. These analogues are suitable for mealtime blood glucose control as they simulate pulsatile insulin secretion during meals. Secondly, long acting insulin analogues characterized by delayed absorption and peakless activity profile were developed to mimic basal insulin secretion between meals and through the night. An example is provided by Lantus, a medicinal product containing ArgB31–ArgB32, A21 ? Gly or recently published recombinant insulin LysB31–ArgB32. The pharmaceutical motivation for the addition of a dibasic tag at the end of the B-chain is to shift the isoelectric point from 5 to 7, thus leading an acidic formulation (at pH 4.0) to undergo isoelectric precipitation at physiological pH in the subcutaneous tissue. Such precipitation is accompanied by zinc insulin hexamer and provides a ‘long-acting depot’, which is redissolved slowly and absorbed into the bloodstream lasting for about 24 h (Lepore et al. 2000). Another way of protraction hypoglycaemic activity of insulin is to attach fatty acids to insulin, which forms a reversible complex with serum albumin. The binding occurs through the fatty acid moiety. As an example, insulin detemir has been developed by the removal of threonine from the position B30 and acylation of the C14 fatty acid chain (myristic acid) at position 29 on the B Electronic supplementary material The online version of this article (doi:10.1007/s10858-013-9713-2) contains supplementary material, which is available to authorized users.

Coupling reactions between flavylium ions and catechin

In order to model natural polymeric pigments present in old red wines, new covalent adducts have been synthesized upon condensation of synthetic flavylium ions (models of anthocyanins) with catechin (model of tannins) in the presence and in the absence of acetaldehyde. These new pigments have been investigated by 1D and 2D NMR, HPLC, FAB-mass and UV-visible spectroscopies and molecular modelling. The two flavylium salts used in this work (3,4′-dimethoxy-7-hydroxyflavylium chloride and 5,7-dihydroxy-3,4′-dimethoxyflavylium chloride) display quite different reactivities toward catechin. The electronic donating effect of the catechin moiety and the formation of noncovalent dimers in acidic aqueous or methanolic solution should be mainly responsible for the improved stability of the flavylium chromophore in the new pigments.

Functional analysis of the cysteine residues of activin A.

Site-directed mutagenesis and mammalian cell expression was used to analyze the function of each of the 13 cysteine residues in the human activin A beta-subunit precursor. Substitution of the four cysteine residues in the proregion with alanine residues did not affect the function of the proregion in facilitating the dimerization and secretion of activin A homodimers. A series of activin mutants were constructed in which the nine cysteine residues (amino acids 4, 11, 12, 40, 44, 80, 81, 113, and 115) in the mature 116-amino acid beta-subunit were individually altered to alanine residues. Alanine substitution at either cysteine residues 4 or 12 did not interfere with homodimer formation, but the mutant activin A molecules had reduced biological and receptor binding activity (2- to 3-fold). Activin A monomers were produced when cysteine mutants 44, 80, and 113 were expressed in tissue culture cells. Monomers of cys mutants 44 and 80 had approximately 2% of the biological and receptor binding activity of wild type activin A. Cys 113 monomers had undetectable levels of biological activity. No detectable activin monomers or dimers were secreted from cells transfected with plasmids containing cys mutants 11, 40, 81, and 115. The data presented here suggest that a low level of noncovalent dimer formation of cysteine mutant monomers 44 and 80 may explain their low level of biological activity. Therefore, dimer formation is suggested to be an essential prerequisite for high affinity receptor binding and biological potency.(ABSTRACT TRUNCATED AT 250 WORDS)