Acetyl-L-tyrosine methyl amide

The nature of carbohydrate binding first to p-hydroxy toluene and then the capped amino acid, N-acetyl l-tyrosine methyl amide (AcTyrNHMe), has been investigated in a solvent-free environment under molecular beam conditions. A combination of double resonance IR-UV spectroscopy and quantum chemical calculations has established the structures of complexes with the α and β anomers of methyl d-gluco- and d-galacto- and l-fucopyranosides (α/βMeGlc, MeGal, MeFuc). The new results, when combined with dispersion-corrected DFT calculations, reveal gas phase structures which are dominated by hydrogen bonding but also with evidence of CH-π bonded interactions in complexes with α/βMeGal. These adopt stacked intermolecular structures in marked contrast to those with α/βMeGlc; p-OH → O bonds linking AcTyrNHMe, or p-hydroxy toluene, to the carbohydrate provide an anchor that facilitates further binding, both through OH → O and NH → O hydrogen bonds to the peptide backbone and through CH-π dispersion interactions with the aromatic side group. "Stacked" structures associated with dispersion interactions with the aromatic ring are not detected in the corresponding complexes of capped phenylalanine, despite their common occurrence in bound carbohydrate-protein structures.

The title compound, C(11)H(11)Br(2)NO(4)·0.5H(2)O, was prepared by an electrophilic bromination of N-acetyl-l-tyrosine in acetonitrile at room temperature. The two independent mol-ecules do not differ substanti-ally and a mol-ecule of water completes the asymmetric unit. The synthesis of the title compound does not modify the stereochemical center, as shown by the absolute configuration found in this crystal structure. Comparison with the non-bromo starting material differs mainly by rotation features. For instance the H(methine)-C(chiral center)-C(methyl-ene)-C(ipso) is 173.0 (2)° torsion angle in one mol-ecule and 177.3 (2)° in the other, indicating a trans arrangement. This is in contrast with approximately 50° in the starting material. A short inter-molecular Br⋯Br separation is observed [3.2938 (3) Å]. The molecules in the crystal are connected via a network of hydrogen bonds through an N-H⋯O hydrogen bond between the hydroxy group of the phenol of the tyrosine and the N-H of the amide of the other molecule and an O-H⋯O hydrogen bond between the hydroxy group of the carboxylic acid and the oxygen of the carbonyl of the amide.

The steady-state and time-resolved fluorescence spectroscopy was applied to determine the influence of an alkyl substituent(s) (methyl or ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, or t-butyl) on amide nitrogen atom on photophysical properties of tyrosine and N-acetyltyrosine amides in water. Generally, the amide group strongly quenches the fluorescence of tyrosine, however, the size and number of substituents on amide nitrogen atom modify the quenching process only in small degree. The fluorescence intensity decays of all amides studied are bi-exponential. The contribution of both components (alphai) to the fluorescence decay undergoes irregular change. An introduction of alkyl substituent on amide nitrogen atom causes an increase of the fluorescence lifetime of tyrosine derivative compared to the unsubstituted amide for both N-acetyltyrosine and tyrosine with the protonated amino group. Calculated, basing on the fluorescence quantum yield (QY) and average lifetime, the radiative rate constants (kf) are similar, which indicates that the substituent(s) does not have substantial influence on radiative process of the deactivation of the excited state of the phenol chromophore for all compounds studied regardless the amino group status as well as the number and type of substituent (linear or branched). The comparison of the ground-state rotamer populations of tyrosine amides and N-acetyltyrosine amides with different alkyl substituent on amide nitrogen atom obtained from 1H NMR with the value of pre-exponential factors indicates that not the rotamer populations, but specific hydration of a whole molecule of the amino acid including chromophore and amino acid moiety, seems to be the main reason of the heterogenous fluorescence intensity decay of tyrosine derivatives.