Evaluation of Electronic Effects in the Solvolyses ofp-Methylphenyl andp-Chlorophenyl Chlorothionoformate Esters

Abstract

The solvolyses of p-tolyl chlorothionoformate and p-chlorophenyl chlorothionoformate are studied in a variety of organic mixtures of widely varying nucleophilicity and ionizing power values. This solvolytic data is accumulated at 25.0 °C using the titration method. An analysis of the rate data using the extended (two-term) Grunwald-Winstein equation, and the concept of similarity of substrates based on their l/m ratios, shows the occurrence of simultaneous side-by-side addition-elimination and unimolecular SN1 mechanisms.

Correlating Coating Characteristics with the Performance of Drug-Coated Balloons – A Comparative In Vitro Investigation of Own Established Hydrogel- and Ionic Liquid-Based Coating Matrices

“…Searching for an explanation, we measured the coating thickness without PTX to underline the statement of different grades of drug incorporation into the two hydrogels. As mentioned in [ 13 ], the coating thickness of the HA coating without PTX is about 2.8 μm. In contrast, we measured a coating thickness of about 9.7 μm for the PVP coating without PTX incorporation ( S1 Table ) which is nearly a triple of the coating thickness and may additionally underline that PVP can surround the drug better than HA.…”

“…While the Cetpyrsal/PTX coating is pipetted in one step from a single solution, the hydrogel-based DCB were coated in a two-step process firstly either dipping (HA) or spraying (PVP) and secondly pipetting the PTX on the hydrogel coating. The two step process was however necessary when applying hydrogels in order to provide sufficient crosslinking and thereby decreased water solubility of hydrogels afforded for minimized drug loss during simulated use as shown in previous studies [ 13 ] [ 14 ] without affecting PTX availability and stability. For instance, applying PTX with HA or PVP in one step and performing hydrogel crosslinking with EDC/NHS or UV light irradiation, respectively, in presence of PTX might either cause its crosslinking within the hydrogels as described in [ 13 ] [ 14 ] [ 25 ] [ 26 ] or in case of UV light irradiation even its photodecomposition [ 14 ] [ 27 ] [ 28 ].…”

“…The HA-based coating was developed and optimized with regard to adherence to the balloon surface and crosslinking condition in our previous research [ 13 ]. Optimized coating conditions were applied here.…”

“…In this regard, we developed and established three different matrices for DCB based on (i) the ionic liquid (IL) cetylpyridinium salicylate (Cetpyrsal) [ 12 ], (ii) the natural and body-own hydrogel hyaluronic acid (HA) [ 13 ] and (iii) the synthetic but pharmaceutically often applied hydrogel polyvinylpyrrolidone (PVP) [ 14 ] in previous studies. We considered IL as attractive matrix for DCB, because important physical, chemical and biological properties are tunable [ 15 ] by combination of various e.g.…”

“…In our first in vitro studies, the IL- and both hydrogel-based coatings evidenced good performance with regard to drug loss and transfer. For example, we determined drug wash-off rates of 28% for the Cetpyrsal/PTX, < 5% for the HA/PTX and 34% for the PVP/PTX coating and drug transfer rates of 40%, 50% and 49%, respectively [ 12 ] [ 13 ] [ 14 ]. Although values are not comparable as different in vitro models were used for their determination, we like to conclude from these data that the application of either IL or hydrogels approved as promising matrices for DCB at first sight.…”