A computational investigation of nucleation processes in organic crystals

Nucleation processes are ubiquitous in nature and technology. For instance, cloud formation in the atmosphere, the casting of metals, protein crystallization, biomineralization, the production of porous materials, and separation of pharmaceutical compounds from solution are a few examples of relevant nucleation processes. One pathway for nucleation to occur is homogeneous nucleation, in which an embryo of a more stable phase forms within an original metastable medium. Homogeneous nucleation is an activated process, meaning that a free energy barrier must be overcome for the transition to take place, and the height of the free energy barrier determines the rate at which the process will occur. Despite considerable advances in both theoretical and experimental techniques to date, determining nucleation mechanisms for real systems remains a considerable technical challenge. The aim of this thesis is therefore to apply molecular simulation techniques to elucidate nucleation mechanisms in organic crystals. Specifically, the newly developed methods of aimless shooting and likelihood maximization are applied for the first time to study nucleation processes in complex and technically relevant systems. The first portion of the thesis examines polymorphism, or the ability of a material to pack in different crystal lattices whilst retaining the same chemical composition. Transformation to a more stable polymorph can readily occur in the solid state, which has broad implications in pharmaceutical processing. To date, over 160 mechanisms have been proposed for polymorph transitions in the solid state, but none have been definitively verified. A model compound, terephthalic acid, is chosen for computational studies because it is similar in size to a small molecule therapeutic and exhibits a common bonding motif for organic crystals. Using aimless shooting and likelihood maximization, the mechanism of the solid state polymorph transformation in terephthalic acid is shown to be comer nucleation. The mechanism shows that for a given nucleus size, the interfacial area between the crystalline domains is minimized, thus reducing the unfavorable surface free energy penalty required for nucleation to occur.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Beckham, Gregg Tyler

Advisor dc:contributor.advisor

• Bernhardt L. Trout.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/42433

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/42433