Potentiometric investigation of the stability of palladium(II) complex of pralidoxime chloride in aqueous solution

Specific and Cooperative Interactions between Oximes and PAMAM Dendrimers As Demonstrated by 1H NMR Study

“…On the basis of the NMR titration experiment, we hypothesize that the tertiary amine group serves as the individual receptor site for the oxime drug molecule, and the primary interaction occurs between the tertiary nitrogen and the oxime moiety (=NOH). However, the basicity of the tertiary amine for this dendrimer (pK a = 6.3−6.85 for its conjugate acid 57 ) is not sufficiently strong for full deprotonation of the oxime proton (=NOH; pK a = 8.1 55 ). Thus, we hypothesize that the drug binding occurs instead through the H-bond, or partial ionic interaction that does not involve a full charge separation.…”

“…In the prior study performed with G5-NH 2 , we hypothesized that electrostatic interaction is the driving force for the binding of the 2-PAM molecule (p K a of −NOH = 8.1) to the terminal primary amine (p K a = 9.0–10.77 for its conjugated acid). One of the experiments we performed for verifying this interaction model was to compare reference 2-PAM solutions, each prepared in a relevant salt form by mixing with an equimolar amount of a small amine molecule having the same basicity.…”

Design and mechanistic investigation of oxime-conjugated PAMAM dendrimers as the catalytic scavenger of reactive organophosphate

“…3, the rate determining step of POX hydrolysis involves the nucleophilic attack of a POX molecule by an oxime or hydroxamate moiety carried by the antidote molecule and dendrimer conjugate. Each of these catalytic residues is weakly acidic with pK a values of 7.8-8.1 (]NOH) 54,55 for 4-PAM and 9.0-9.5 (C(]O)NHOH) 48,56 for GHA (Table 1), and becomes more reactive as the POX-attacking nucleophile is deprotonated (]NO À , C(]O)NHO À ). In order to gain more insight on this nucleophilic mechanism, we performed POX hydrolysis experiments under alkaline conditions at pH 9.0, at which the fraction of deprotonated oxime or hydroxamate units is higher than the neutral pH 7.4.…”

Specificity and Negative Cooperativity in Dendrimer–Oxime Drug Complexation

“…Given the p K a of 2-PAM (8.1), lower than the p K a of a terminal primary amine (9.0–10.77), we hypothesize that electrostatic interaction is the driving force for the drug complexation (Figure ). We verified this hypothesis by measuring the 1 H NMR spectra of 2-PAM mixed with an equimolar amount of triethylamine (p K a = 10.78) and of ethanolamine (p K a = 9.50).…”