Entropy-driven population distributions in a prototypical molecule with two flexible side chains: O -(2-acetamidoethyl)- N -acetyltyramine

Abstract

Resonant two-photon ionization (R2PI), resonant ion-dip infrared (RIDIR), and UV-UV hole-burning spectroscopies have been employed to obtain conformation-specific infrared and ultraviolet spectra under supersonic expansion conditions for O -(2-acetamidoethyl)- N -acetyltyramine (OANAT), a doubly substituted aromatic in which amide-containing alkyl and alkoxy side chains are located in para positions on a phenyl ring. For comparison, three single-chain analogs were also studied: (i) N -phenethyl-acetamide (NPEA), (ii) N - (p -methoxyphenethyl-acetamide) (NMPEA), and (iii) N -(2-phenoxyethyl)- acetamide (NPOEA). Six conformations of OANAT have been resolved, with S0 - S1 origins ranging from 34 536 to 35 711 cm-1, denoted A-F, respectively. RIDIR spectra show that conformers A-C each possess an intense, broadened amide NH stretch fundamental shifted below 3400 cm-1, indicative of the presence of an interchain H bond, while conformers D-F have both amide NH stretch fundamentals in the 3480-3495 cm-1 region, consistent with independent-chain structures with two free NH groups. NPEA has a single conformer with S0 - S1 origin at 37 618 cm-1. NMPEA has three conformers, two that dominate the R2P1 spectrum, with origin transitions between 35 580 and 35 632 cm-1. Four conformations, one dominate and three minor, of NPOEA have been resolved with origins between 35 654 and 36 423 cm-1. To aid the making of conformational assignments, the geometries of low-lying structures of all four molecules have been optimized and the associated harmonic vibrational frequencies calculated using density functional theory (DFT) and RIMP2 methods. The S0 - S1 adiabatic excitation energies have been calculated using the RICC2 method and vertical excitation energies using single-point time-dependent DFT. The sensitivity of the S0 - S1 energy separation in OANAT and NPOEA primarily arises from different orientations of the chain attached to the phenoxy group. Using the results of the single-chain analogs, tentative assignments have been made for the observed conformers of OANAT. The RIMP2 calculations predict that interchain H-bonded conformers of OANAT are 25-30 kJmol more stable than the extended-chain structures. However, the free energies of the interchain H-bonded and extended structures calculated at the preexpansion temperature (450 K) differ by less than 10 kJmol, and the number of extended structures far outweighs the number of H-bonded conformers. This entropy-driven effect explains the presence of the independent-chain conformers in the expansion, and cautions future studies that rely solely on relative energies of conformers in considering possible assignments. © 2007 American Institute of Physics.