title: Proximity effects in monolayer films: kinetic analysis of amide bond formation at the air-water interface using (1)H NMR spectroscopy.
abstract: The kinetics of amide bond formation in a monolayer film has been studied by proton NMR spectroscopy. Compression of a hexadecyl thioester of N-acetyl glycine (1) and a hexadecyl amide of glycine (2) at the air-water interface produces a single dipeptide product (4) that remains at the surface once formed. Extraction of the reaction mixture from the interface, followed by (1)H NMR spectroscopy, provides quantitative data on the rate of product formation. The kinetics of this reaction was examined as a function of surface pressure, subphase pH, and temperature. The monolayer provides an effective molarity for the reaction of approximately 500 M as compared to the bimolecular reaction of 1 and 4 in chloroform solution. The first-order rate constant for the reaction of 1 and 2 in the monolayer is less than 70-fold slower than k(cat) for condensation of the first amide bond in the enzymatic synthesis of the cyclic antibiotic gramicidin S by gramicidin S synthetase. Activation energies of the reaction were extracted from the temperature dependence of the rate constants of the reaction and are 9.9 +/- 1.0 and 2.1 +/- 0.2 kcal/mol for the chloroform solution and monolayer reactions, respectively. The pK(a) of 2 in the monolayer was estimated to be approximately 0.5 pK(a) units lower than that of related amines in solution. The lower pK(a) at the interface as compared to that in solution may be ascribed to increased electrostatic repulsion at the interface relative to solution. The rate of reaction in the monolayer was also followed by monitoring changes in surface area as a function of time. The rate constant for the reaction of 1 and 4 as determined by changes in surface area differs significantly from the rate determined by NMR. The results indicate that measurements of surface area versus time may yield erroneous rate constants for reactions in monolayers.
authors.affiliation: Department of Chemistry, Box H, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Jaya K
authors.initials: JK
authors.lastname: Kumar
authors.forename: John S
authors.initials: JS
authors.lastname: Oliver
mesh_terms: D000388:Air; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011522:Protons; D013499:Surface Properties; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D000577:Amides; D011522:Protons; D014867:Water; D005998:Glycine