3 research outputs found
Decomposition of <i>N</i>āChloroglycine 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<sup>ā</sup>] = 0.01ā0.10 M). The absorbance change is consistent with
two consecutive first-order processes in the 220ā350 nm wavelength
range. The first reaction is linearly dependent on [OH<sup>ā</sup>] and interpreted by the formation of a carbanion from MCG in an
equilibrium step (<i>K</i><sub>OH</sub>) and a subsequent
loss of chloride ion from this intermediate: <i>k</i><sub>obs1</sub> = <i>K</i><sub>OH</sub> <i>k</i><sub>1</sub> = (6.4 Ā± 0.1) Ć 10<sup>ā2</sup> M<sup>ā1</sup> s<sup>ā1</sup>, <i>I</i> = 1.0 M (NaClO<sub>4</sub>), and <i>T</i> = 25.0 Ā°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><sub>obs2</sub> = (1.2 Ā± 0.1) Ć 10<sup>ā3</sup> s<sup>ā1</sup>. Systematic <sup>1</sup>H and <sup>13</sup>C 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-Phenanthrolineā<i>N</i>,<i>N</i>ā²ādioxide 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>ā²<i>-</i>dioxide (phenO<sub>2</sub>) 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 H<sub>2</sub>SO<sub>4</sub>, 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 ā¼6.7. The formation
of phenO occurs via two parallel pathways: the rate constant of the
oxidation of phen (<i>k</i> = 3.1 Ā± 0.1 M<sup>ā1</sup> s<sup>ā1</sup>) is significantly larger than that of Hphen<sup>+</sup> [<i>k</i> = (4.1 Ā± 0.3) Ć 10<sup>ā3</sup> M<sup>ā1</sup> s<sup>ā1</sup>] 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 phenO<sub>2</sub> in the second step. The formation of phenO<sub>2</sub> was confirmed by <sup>1</sup>H NMR and ESI-MS methods. The
results presented here offer the possibility of designing an experimental
protocol for preparing phenO<sub>2</sub>
Rational Design of Ī±āHelix-Stabilized Exendinā4 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 moleculeās 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 <sup>15</sup>N 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