Decomposition of <i>N</i>‑Chloroglycine in Alkaline Aqueous Solution: Kinetics and Mechanism

The decomposition kinetics and mechanism of <i>N</i>-chloroglycine (MCG) was studied under very alkaline conditions ([OH^–] = 0.01–0.10 M). The absorbance change is consistent with two consecutive first-order processes in the 220–350 nm wavelength range. The first reaction is linearly dependent on [OH^–] and interpreted by the formation of a carbanion from MCG in an equilibrium step (<i>K</i>_OH) and a subsequent loss of chloride ion from this intermediate: <i>k</i>_obs1 = <i>K</i>_OH <i>k</i>₁ = (6.4 ± 0.1) × 10^–2 M^–1 s^–1, <i>I</i> = 1.0 M (NaClO₄), and <i>T</i> = 25.0 °C. The second process is assigned to the first-order decomposition of <i>N</i>-oxalylglycine, which is also formed as an intermediate in this system: <i>k</i>_obs2 = (1.2 ± 0.1) × 10^–3 s^–1. Systematic ¹H and ¹³C NMR measurements were performed in order to identify and follow the concentration changes of the reactant, intermediate, and product. It is confirmed that the decomposition proceeds via the formation of glyoxylate ion and produces <i>N</i>-formylglycine as a final product. This compound is stable for an extended period of time but eventually hydrolyses into formate and glycinate ions. A detailed mechanism is postulated which resolves the controversies found in earlier literature results

Formation of 1,10-Phenanthroline‑<i>N</i>,<i>N</i>′‑dioxide under Mild Conditions: The Kinetics and Mechanism of the Oxidation of 1,10-Phenanthroline by Peroxomonosulfate Ion (Oxone)

This paper confirms the unexpected formation of 1,10-phenanthroline-<i>N</i>,<i>N</i>′<i>-</i>dioxide (phenO₂) when 1,10-phenanthroline (phen) is oxidized by peroxomonosulfate ion (PMS) in a neutral aqueous solution. The kinetics of oxidation of phen by PMS features a complex pH dependence. In 1.00 M H₂SO₄, 1,10-phenanthroline-mono-<i>N</i>-oxide (phenO) is the sole product of the reaction. The rate of the N-oxidation is highly dependent on pH with a maximum at pH ∼6.7. The formation of phenO occurs via two parallel pathways: the rate constant of the oxidation of phen (<i>k</i> = 3.1 ± 0.1 M^–1 s^–1) is significantly larger than that of Hphen⁺ [<i>k</i> = (4.1 ± 0.3) × 10^–3 M^–1 s^–1] because the two N atoms are open to oxidative attack in the deprotonated substrate while an internal hydrogen bond hinders the oxidation of the protonated form. With an excess of PMS, four consecutive oxidation steps were found in nearly neutral solutions. In the early stage of the reaction, the stepwise oxidation results in the formation of phenO, which is converted into phenO₂ in the second step. The formation of phenO₂ was confirmed by ¹H NMR and ESI-MS methods. The results presented here offer the possibility of designing an experimental protocol for preparing phenO₂

Rational Design of α‑Helix-Stabilized Exendin‑4 Analogues

Exendin-4 (Ex4) is a potent glucagon-like peptide-1 receptor agonist, a drug regulating the plasma glucose level of patients suffering from type 2 diabetes. The molecule’s poor solubility and its readiness to form aggregates increase the likelihood of unwanted side effects. Therefore, we designed Ex4 analogues with improved structural characteristics and better water solubility. Rational design was started from the parent 20-amino acid, well-folded Trp cage (TC) miniprotein and involved the step-by-step N-terminal elongation of the TC head, resulting in the 39-amino acid Ex4 analogue, E19. Helical propensity coupled to tertiary structure compactness was monitored and quantitatively analyzed by electronic circular dichroism and nuclear magnetic resonance (NMR) spectroscopy for the 14 peptides of different lengths. Both ¹⁵N relaxation- and diffusion-ordered NMR measurements were established to investigate the inherent mobility and self-association propensity of Ex4 and E19. Our designed E19 molecule has the same tertiary structure as Ex4 but is more helical than Ex4 under all studied conditions; it is less prone to oligomerization and has preserved biological activity. These conditions make E19 a perfect lead compound for further drug discovery. We believe that this structural study improves our understanding of the relationship between local molecular features and global physicochemical properties such as water solubility and could help in the development of more potent Ex4 analogues with improved pharmacokinetic properties