(53g) Modeling Minimum Free Energy Path for Crystallization of Drug Molecules in Different Solvents
AIChE Annual Meeting
2016
2016 AIChE Annual Meeting
Engineering Sciences and Fundamentals
Thermodynamics Needs of the Chemical Industry
Sunday, November 13, 2016 - 5:35pm to 5:55pm
Firstly, force field parameters for sulfadiazine and sulfamerazine were developed using the CHARMM general force field (CGenFF). The partial charges were modified to reproduce interactions with explicit TIP3P water molecules at quantum mechanical level of theory. The bond, angle and dihedral parameters were optimized by fitting them to yield a minimum energy geometry while capturing the potential energy surface calculated by quantum mechanics. The structural error of the unit cell parameters for sulfadiazine decreased from 3-8% before optimization to 0.3-1.5% after refitting the parameters. For sulfamerazine, the error decreased from 6.7-11.6% to 0.1-1.8%. Secondly, we constructed order parameters (OPs) from a generalized pair distribution function which gives the probability that a molecule with a particular internal configuration has a neighboring molecule with a given internal configuration, a given center of mass distance away from the first molecule and a given orientation with respect to the first molecule. The OPs of bond orientation and relative orientation have well separated distributions and both are able to quantitatively distinguish between liquid and solid states of the drug molecules. Finally, the minimum free energy paths were determined by using string method in collective variables while the constructed OPs parameterized the â??reaction coordinateâ? during the crystallization of sulfadiazine and sulfamerazine from their liquid states to solid states.