Determination of non-covalent docking by IR spectroscopy of cold gas-phase complexes

• Published in: Science (American Association for the Advancement of Science) 2012-01, Vol.335 (6069), p.694-698
• Main Authors: Garand, Etienne, Kamrath, Michael Z., Jordan, Peter A., Wolk, Arron B., Leavitt, Christopher M., McCoy, Anne B., Miller, Scott J., Johnson, Mark A.
• Format: Article
• Language: English
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1214948

Multi-dentate, non-covalent interactions between small molecules and biopolymer fragments are central to processes ranging from drug action to selective catalysis. We present a versatile and sensitive spectroscopic probe of functional groups engaged in hydrogen bonding in such contexts. This involves measurement of the frequency changes in specific covalent bonds upon complex formation, information drawn from otherwise transient complexes that have been extracted from solution and conformationally frozen near 10 Kelvin in gas-phase clusters. Resonances closely associated with individual oscillators are easily identified through site-specific isotopic labeling, as demonstrated by application of the method to an archetypal system involving a synthetic tripeptide known to bind biaryl substrates through tailored H-bonding to catalyze their asymmetric bromination. With such data, calculations readily converge on the plausible operative structures in otherwise computationally prohibitive, high dimensionality landscapes.