Computational Simulations to Aid in the Experimental Discovery of Ice Recrystallization Inhibitors and Ultra-Microporous Metal Organic Frameworks

Title: Computational Simulations to Aid in the Experimental Discovery of Ice Recrystallization Inhibitors and Ultra-Microporous Metal Organic Frameworks
Authors: De Luna, Phil
Date: 2015
Abstract: In this thesis computational chemistry has been used to accelerate experimental discovery in the fields of ice recrystallization inhibitors for cryopreservation and ultra-microporous MOFs for carbon dioxide capture and storage. Ice recrystallization is one of the leading contributors to cell damage and death during the freezing process. This occurs when larger ice crystal grains grow at the expense of smaller ones. Naturally occurring biological antifreeze molecules have been discovered but only operate up to -4oC and actually exasperate the problem at temperatures lower than this. Recently, the group of Dr. Robert Ben have been successful in synthesizing small organic molecules which are capable of inhibiting the growth of ice crystals during the freezing process. They have built a library of diverse compounds with varying functionalities and activity. Chemical intuition has been unsuccessful in finding a discernible trend with which to predict activity. Herein we present work where we have utilized a quantitative structure activity relationship (QSAR) model to predict whether a molecule is active or inactive. This was built from a database of 124 structures and was found to have a positive find rate of 82%. Proposed molecules that had yet to be synthesized were predicted to active or inactive using our method and 9/11 structures were indeed active which is strikingly consistent to the 82% find rate. Our efforts to aid in the discovery of these novel molecules will be described here. Metal organic frameworks (MOFs) are a relatively new class of porous materials which have taken the academic community by storm. These three-dimensional crystalline materials are built from a metal node and an organic linker. Depending on the metals and organic linkers used, MOFs can possess a vast range of topologies and properties that can be exploited for specific applications. Ultra-microporous MOFs possess relatively small pores in the range of 3.5 Å to 6 Å in diameter. These MOFs have some structural advantages compared to larger pored MOFs such as molecular sieving, smaller pores which promote strong framework-gas interactions and cooperative effects between guests, and longer shelf-life due to small void volumes and rigid frameworks. Here we present newly synthesized ultra-microporous MOFs based on isonicotnic acid as the organic linker with Ni and Mg as the metal centre. Despite having such small pores, Ni-4PyC exhibits exceptionally high CO2 uptake at high pressures. Furthermore, Mg-4PyC exhibits novel pressure dependent gate-opening behaviour. Computational simulations were employed to investigate the origin of high CO2 uptake, predict high pressure (>10bar) isotherms, quantify CO2 binding site positions and energies, and study uptake-dependent linker dynamics. This work hopes to provide experimentalists with some explanation to these interesting unexplained phenomena and also predict optimal properties for new applications.
CollectionThèses, 2011 - // Theses, 2011 -