Rustenburg, Arien S.; Dancer, Justin; Lin, Baiwei; Feng, Jianwen A.; Ortwine, Daniel F.; Mobley, David L.; Chodera, John D. published the artcile< Measuring experimental cyclohexane-water distribution coefficients for the SAMPL5 challenge>, Electric Literature of 5182-90-1, the main research area is cyclohexane water SAMPL5 analysis; Blind challenge; Distribution coefficients; Partition coefficients; Predictive modeling; SAMPL.
Small mol. distribution coefficients between immiscible nonaqueuous and aqueous phases-such as cyclohexane and water-measure the degree to which small mols. prefer one phase over another at a given pH. As distribution coefficients capture both thermodn. effects (the free energy of transfer between phases) and chem. effects (protonation state and tautomer effects in aqueous solution), they provide an exacting test of the thermodn. and chem. accuracy of phys. models without the long correlation times inherent to the prediction of more complex properties of relevance to drug discovery, such as protein-ligand binding affinities. For the SAMPL5 challenge, we carried out a blind prediction exercise in which participants were tasked with the prediction of distribution coefficients to assess its potential as a new route for the evaluation and systematic improvement of predictive phys. models. These measurements are typically performed for octanol-water, but we opted to utilize cyclohexane for the nonpolar phase. Cyclohexane was suggested to avoid issues with the high water content and persistent heterogeneous structure of water-saturated octanol phases, since it has greatly reduced water content and a homogeneous liquid structure. Using a modified shake-flask LC-MS/MS protocol, we collected cyclohexane/water distribution coefficients for a set of 53 druglike compounds at pH 7.4. These measurements were used as the basis for the SAMPL5 Distribution Coefficient Challenge, where 18 research groups predicted these measurements before the exptl. values reported here were released. In this work, we describe the exptl. protocol we utilized for measurement of cyclohexane-water distribution coefficients, report the measured data, propose a new bootstrap-based data anal. procedure to incorporate multiple sources of exptl. error, and provide insights to help guide future iterations of this valuable exercise in predictive modeling.
Journal of Computer-Aided Molecular Design published new progress about pH. 5182-90-1 belongs to class quinoxaline, and the molecular formula is C9H7N3O, Electric Literature of 5182-90-1.
Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider