The deoxynojirimycin (DNJ) family of imino sugars are glucose analogues with an NH group replacing the oxygen atom in the pyranose ring. They are powerful inhibitors of glycosidases and ceramide glucosyltransferases. The conformation of N-benzyl-DNJ, isolated in the gas phase, is studied using a combination of resonant two-photon ionization (R2PI), UV/UV hole-burn, and IR ion-dip spectroscopies in conjunction with electronic structure theory calculations. Three distinct conformers, one major and two minor, are present and all three are assigned to structures in which the exocyclic hydroxymethyl group is axial to the piperidine ring (gauche- to the ring nitrogen). This contrasts with the preferred equatorial (gauche+) orientation observed for simple glucosides and may well contribute to the stronger binding of some enzymes to DNJ-based inhibitors compared to their natural glucoside substrates.

The beta(1-->4) glycosidic linkage found in lactose is a prevalent structural motif in many carbohydrates and glycoconjugates. Using UV and IR ion-dip spectroscopies to probe benzyl lactoside isolated in the gas phase, we find that the disaccharide unit adopts only a single, rigid structure. Its fully resolved infrared ion-dip spectrum is in excellent agreement with that of the global minimum structure computed ab initio. This has glycosidic torsion angles of phi(H) (H1-C1-O-C4') approximately 180 degrees and psi(H) (C1-O-C4'-H4') approximately 0 degrees which correspond to a rotation of approximately 150 degrees about the glycosidic bond compared to the accepted solution-phase conformation. We discuss the biological implications of this discovery and the generality of the strategies employed in making it.

The structural investigation of a hydrated monosaccharide, phenyl beta-D-glucopyranoside (PhebetaGlc), in the gas phase is presented. It is based upon ab initio computation coupled with the analysis of the resonant 2-photon ionization and IR ion-dip spectra of the singly hydrated clusters stabilized in a free jet expansion and follows an earlier investigation of the structure and conformations of the unhydrated sugar.(1) Despite the potentially large set of possible binding sites and conformations, only two singly hydrated complexes are formed in the free jet expansion. Tentative structural assignments are made on the basis of comparisons with those already established for related systems; comparisons between the observed O-H vibrational frequencies and those computed for structures optimized at the B3LYP/6-31+G(d) level of theory, and in light of the relative energies of these structures, calculated at the single-point MP2/6-311+G(d,p) level are made. A discrepancy between the latest revision of the Gaussian 98 package (revision A.11) and earlier revisions, which can lead to different computed structures when optimizing noncovalently bound molecular complexes, is discussed in an appendix.

The gas-phase conformation of the model glycoside, phenyl beta-D-galactopyranoside (phe-beta-D-gal) was examined using a combination of resonant two-photon ionization (R2PI) and resonant ion-dip infrared spectroscopy (RIDIRS) in tandem with electronic structure theory calculations. A single conformer, in which the hydroxy methyl is in a gauche + orientation, is predominant in the free-jet expansion. This conformer is the analogue of the lowest-energy conformer found in a previous study of phenyl beta-D-glucopyranoside. A minor second conformer has also been identified. Other weak bands in the R2PI spectrum have been attributed to hot bands though it is possible that other conformers are also present at low abundance. The dominant conformer identified in this work has the same (gauche +) orientation of the hydroxy methyl group as the major rotamer identified in solution by NMR spectroscopy.

Mass-resolved resonant two photon ionisation (R2PI) and infrared ion dip spectra have been recorded for 4-phenylimidazole (4PI) and its singly and multiply hydrated clusters 4PI(H2O)n = 0 - 4, under supersonic expansion conditions. In the case of 4PI(H2O)0,1, it has also been possible to record infrared spectra in both the ground (S0) and excited (S1) states. Combining the experimental data with the results of ab initio calculations has led to the structural assignment of each cluster. In each case, the water molecules bind primarily to the NH site of the imidazole ring. Clusters with n≥ 2 incorporate linear water chains, in which the proton donating terminus bridges either to the π-electron system (n = 2) or to the >N: atom site (n = 3, 4) on the imidazole ring. Despite the creation of a “water wire”, connecting the donor and acceptor sites of imidazole, there is no evidence of proton transfer in either the ground or excited state.

The first spectroscopic investigation and full structural assignment of a model glycoside in the gas phase, namely phenyl beta-D-glucopyranoside, is reported, based upon measurements of its resonant two photon ionisation and infra-red ion dip spectra together with supporting ab initio calculations. Three conformers ( two gauche and one trans) were identified and structurally assigned. A comparison with the predictions of earlier high-level ab initio calculations on the unsubstituted sugar,(13,14) indicate that the addition of a phenyl substituent at position 1 on the pyranoside ring, has very little effect on the low energy region of its conformational landscape.