A computationally derived structural model of doxorubicin interacting with oligomeric polyalkylcyanoacrylate in nanoparticles.

We report a molecular simulation study of doxorubicin interacting within a frame of n-butyl polycyanoacrylate, one of the most commonly encountered polymers in the production of nanoparticles. Emphasis is put on the tetrameric, hexameric and octameric oligomers (PACA's). Log P was calculated for all interacting species. Molecular dynamics along with energy minimization processes (molecular mechanics MM2, semi-empirical quantum mechanics PM3) were employed to probe the conformational behavior of doxorubicin and polyalkylcyanoacrylate both as isolated species and interacting with each other. A docked structure of protonated doxorubicin with two octamers of n-butyl polycyanoacrylate is described. Among the main stability factors of the assembly was the charge-dipole interaction representing a stabilizing contribution of -33 kcal/mol. The mechanism of aggregation and desegregation (doxorubicin release) can be summarized as follows: oligomeric PACA's are lipophilic entities that scavenge amphiphilic doxorubicin already during the polymerization process by extraction of the protonated species from the aqueous environment to the increasingly lipophilic phase of the growing PACA's. The establishment of hydrogen bonds between the ammonium N-H function and the cyano groups is noteworthy. The cohesion in PACA nanoparticle comes therefore from a blend of dipole-charge interaction, H bonds, and hydrophobic forces

A simple and effective method for the thionation of amides to thioamides using Al2O3-supported P4S10

A simple and effective method for the thionation of amides to thioamides using Al2O3-supported F4S10 was developed and applied to a series of amides including some heterocyclic examples, The reaction was best performed in anhydrous dioxane at reflux temperature. Yields ranging from 62 - 93% are comparable to, or superior to those obtained with Lawesson's reagent. The method uses inexpensive reagents and has the advantage that reagent-derived byproducts may be removed by a simple hydrolytic workup rather than by chromatography, as required for Lawesson's reagent