Computer-Aided Chemistry Laboratory Speeds Research

Laboratory Note
State-of-the-art Computer-Aided Chemistry
Laboratory Speeds Research

Alan Welch

Introduction

The skills that chemists require have changed considerably over the past 20-25 years. Synthetic chemists now routinely use complex techniques such as nuclear magnetic resonance (NMR) spectroscopy and X-ray diffraction to answer their research questions. Molecular modeling is a simple extension of these techniques that allows researchers to predict the activity of candidate molecules before spending valuable time and resources on synthesis.

We have shown the value of this approach in our research into polyhedral boranes. Boranes and heteroboranes are, in a formal sense, deficient in electrons; this leads directly to their polyhedral structures. Because these compounds are already conformationally restricted, chemists thought they could reliably predict their structures without resorting to complex molecular modeling studies. However, an increasing number of polyhedral boranes have been identified which adopt shapes that are not predicted by these rules. As part of our ongoing studies into chemical structure and bonding, molecular modeling, using the computer-aided molecular design (CAMD) software from companies such as Oxford Molecular Group, has been used to identify polyhedral boranes that will adopt non-standard structures. CAMD software can be used to identify potentially interesting compounds before synthesis and to model the electronic structures of molecules that adopt unusual shapes. Studies such as these provide a unique insight into chemical bonding.

Computer-aided chemistry, such as the CAChe system from CAChe Scientific, a wholly owned subsidiary of Oxford Molecular Group, has been used to predict the structures of various polyhedral boranes. Using this system, molecules that will adopt unusual shapes, for example molecules with broken carbon-carbon bonds, can be identified before spending considerable time and resources on synthesis.

One recently synthesised rule-bending compound is the rhodium carborane CpRhPh2C2B9H9 (CP rhodium). Structural studies found that CP rhodium has a broken carbon-carbon bond on the polyhedral surface; further NMR studies showed that this broken bond was associated with an unusual electronic structure. Molecular modeling studies were used to explore this unusual electronic structure, with the aim of identifying similar molecules and ultimately improving our understanding of chemical bonding.

The CAChe studies showed that the frontier orbitals of CP rhodium were heavily localized on the rhodium atom, rather than being associated with the ruptured bond, as would have been expected. As a result, we learned that synthesizing the apparently obvious reduction/oxidation derivatives of CP rhodium would not yield molecules with new, unusual structural or electronic changes. Thus, we did not waste time and effort on the apparently obvious experiments. Instead, we are concentrating on developing our CAChe models to identify potentially interesting molecules to synthesize.

Targeting Research Efforts

As these studies demonstrate, molecular modeling can help target research efforts onto compounds which may have the desired properties. Studies such as these are not only essential for research chemists working in academic laboratories but also for those whose career takes them into industrial research settings. Industrial research & development laboratories are increasingly concerned to maximize the success rate of their drug and chemical discovery programs by ensuring that a higher proportion of compounds synthesized have at least some of the desired properties.

For this reason, the Chemistry Department at Heriot-Watt University believes that students should learn molecular modeling skills, as well as the now more traditional methods of NMR and other analytical methods. As a result, Heriot-Watt has recently become the first Scottish University, and one of only a few Universities in Europe, to offer a fully equipped CAChe teaching laboratory to its undergraduate students, as well as to researchers and post-graduate students. The chemistry curriculum at Heriot-Watt University will now be able to integrate computational analysis with traditional synthetic techniques and the latest methods for structural determination with the aim of producing graduate chemists who can tackle a wide array of research problems.

Easy-to-Use Interface

The CAChe system interface makes it incredibly easy for researchers and students alike to undertake computational chemistry studies, including molecular mechanical calculations and quantum mechanical calculations. These calculations were possible before, but the user- friendly interface has transformed the ease and speed with which ordinary synthetic chemists in industry or academia can tackle these problems. Twenty-five years ago, only computer specialists could tackle molecular modeling questions and they rarely had the expertise in chemistry to answer complex research questions, now with these easy-to-use systems even undergraduates can learn to use these programs.