Finally, a User-Friendly Way of Computing and Presenting Individual Group Contributions to Polyprotic Ionization of Drugs
Poster Sep 24, 2012
Robert Fraczkiewicz, Marvin Waldman, Robert D. Clark
An extreme example at the other end of the spectrum is mellitic (benzene hexacarboxylic) acid where the six measured apparent pKa’s range from 1.4 to 7.0 – a span of 5.6 orders of magnitude. Assigning each apparent pKa to a specific group is clearly absurd in this case, since the six carboxylic acid groups are completely equivalent. This potentially confusing situation is clarified by considering microscopic ionization equilibria, yielding a precise thermodynamic picture, replacing the inaccurate and misleading “one group = one pKa” paradigm. We have explored microequilibria theory in detail and have developed novel concepts: the pH-dependent Average Single Proton Acidity (ASPA), and the pH-dependent Average Site Protonation profiles (ASP). The ionization midpoint of the latter– the pK50- is pH-independent and closely related to concepts from the physical chemistry of proteins. We show that the pK50, unlike macroscopic pKa, is a transferable property of an individual ionisable group, illustrating its inherent acidity in the absence of intergroup interactions. For example, we calculate a chemically realistic pK50=3.92 for each carboxyl group in mellitic acid. In the case of monoprotic molecules as well as molecules with well-separated ionization patterns, the pK50’s correspond to macroscopic pKa‘s exactly and approximately, respectively. An added bonus is a direct determination of individual site occupancies from the calculated ASP at any pH of interest, which eliminates the need to deduce these quantities from pKa.
CiPA Phase 2 Study: validation of an automated microelectrode array (MEA) assay of hiPSC-derived cardiomyocyte electrophysiology for cardiac safety evaluationPoster
These results support the use of hSC-CM and MEA technology for preclinical assessment of proarrhythmic risk within the proposed CiPA paradigm, and, more generally, demonstrate that automation of the CM-MEA assay can achieve high reliability and throughput for cardiac risk assessment in vitro.READ MORE
A luminescent solar concentrator-based photomicroreactor for energy efficient continuous-flow photocatalysisPoster
The Luminescent Solar ConcentratorPhotomicroreactor
(LSC-PM) is an innovative device
for solar-powered continuous-flow photochemistry.
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Orphan Drugs and Rare Diseases Global Congress 2017 USA
Sep 12 - Sep 14, 2017