title: Determination of noncovalent docking by infrared spectroscopy of cold gas-phase complexes.
abstract: Multidentate, noncovalent 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 hydrogen bonding to catalyze their asymmetric bromination. With such data, calculations readily converge on the plausible operative structures in otherwise computationally prohibitive, high-dimensionality landscapes.
authors.affiliation: Sterling Chemistry Laboratory, Yale University, Post Office Box 208107, New Haven, CT 06520, USA.
authors.forename: Etienne
authors.initials: E
authors.lastname: Garand
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Kamrath
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jordan
authors.forename: Arron B
authors.initials: AB
authors.lastname: Wolk
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Leavitt
authors.forename: Anne B
authors.initials: AB
authors.lastname: McCoy
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Miller
authors.forename: Mark A
authors.initials: MA
authors.lastname: Johnson
mesh_terms: D001665:Binding Sites; D001713:Biphenyl Compounds / Q000737:chemistry*; D002384:Catalysis; D055598:Chemical Phenomena; D005615:Freezing; D005740:Gases; D054879:Halogenation; D006860:Hydrogen Bonding; D007259:Infrared Rays; D008968:Molecular Conformation; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods*; D013237:Stereoisomerism
chemical_list: D001713:Biphenyl Compounds; D005740:Gases; D009842:Oligopeptides