Isabel Hünig

Sugars in the gas phase. Spectroscopy, conformation, hydration, co-operativity and selectivity

The functional importance of carbohydrates in biological processes, particularly those involving specific molecular recognition, is immense. Characterizing the three-dimensional structures of carbohydrates and glycoconjugates and their interactions with other molecules, particularly the ubiquitous solvent, water, are key starting points on the road towards the understanding of these processes. The review introduces a new strategy, combining electronic and vibrational spectroscopy of mass-selected carbohydrate molecules and their hydrated (and also protonated) complexes, conducted under molecular beam conditions, with ab initio computation. Its early successes have revealed a uniquely powerful means of characterizing carbohydrate conformations and hydrated structures, the hydrogen-bonded networks they support (or which support them) and the specificity of their interactions with other molecules. The new information, obtained in the gas phase, complements that provided by more ‘traditional’ condensed phase methods such as NMR, X-ray diffraction, molecular mechanics and molecular dynamics calculations. The review concludes with a vision of the challenges and opportunities offered by applications of molecular beam spectroscopy and their relevance in a biological context. Contents PAGE 1.  Preamble 490 2. Sweetness and light: Sugars in the gas phase 492 3. Experimental and computational strategies 495 4. The conformational landscapes of some key monosaccharides: glucose, galactose, mannose, fucose and xylose 498 4.1. Notation 498 4.2. Glucose, galactose and mannose 499 4.3. Fucose and xylose 503 5. Probing the glycosidic linkage: lactose and glycan ‘building blocks’ 504 5.1. Notation 506 5.2. Lactose 506 5.3. Mannose disaccharides 508 6. Adding water to sugar: hydrogen-bonding, co-operativity and selectivity 512 6.1. Notation 512 6.2. Mono-hydrated complexes: glucose, galactose and mannose 512 6.3. Co-operativity and conformational selectivity 516 6.4. Mono-hydrated complexes: xylose and fucose 519 6.5. Some concluding remarks 521 7. Using sugars: imino sugars and peptide mimics 522 7.1. Sugar mimics: imino sugars 522 7.2. Mimicking peptide secondary structure: carbopeptoids 524 8. Challenges and opportunities 527 Acknowledgements 529 References 530

Conformers of the peptides glycine-tryptophan, tryptophan-glycine and tryptophan-glycine-glycine as revealed by double resonance laser spectroscopy

The peptides Trp-Gly, Gly-Trp and Trp-Gly-Gly were investigated by UV–UV and IR–UV hole burning spectroscopy. Solid samples of the three peptides were vaporised into an argon jet by laser desorption. The IR–UV spectra of different conformers of the peptides were assigned by comparison with the IR–UV spectra of tryptophan [Snoek et al., Phys. Chem. Chem. Phys., 2001, 3, 1819], the free peptide bond in N-acetyl tryptophan methyl amide [Dian et al., J. Chem. Phys., 2002, 117, 10688] and ab initio calculations performed at the DFT B3LYP 6-31G(d,p) level. Apart from an NH⋯NH2 interaction, the peptide backbone of one conformer of each dipeptide is unfolded. The second conformer of Gly-Trp shows a COOH⋯OC hydrogen bond and the second conformer of Trp-Gly-Gly a hydrogen bond between the peptide backbone and the NH group of the indole ring.

The nucleobase cytosine and the cytosine dimer investigated by double resonance laser spectroscopy and ab initio calculations

The vibronic spectrum of laser desorbed and jet cooled cytosine consists of bands from two major tautomers (keto and enol) as revealed by UV-UV and IR-UV double resonance spectroscopy and methyl blocking experiments. Only one isomer each was observed for the cytosine dimer and for the cytosine - 1-methylcytosine mixed dimer. These isomers form CO⋯HNH/NH⋯N hydrogen bonds. Cytosine - 5-methylcytosine exhibits three isomers: one again with CO⋯HNH/NH⋯N connectivity, the second with CO⋯HNH/NH⋯N interaction but one cytosine in the enol form and the third with symmetrical CO⋯NH/NH⋯OC bonds. These are also the most stable clusters according to molecular dynamics/quenching and ab initio quantum chemical calculations. The experimental IR spectra of these isomers agree well with the calculated normal mode vibrational spectra. The vibronic spectra of the clusters are blue shifted relative to the monomer spectra by more than 1000 cm−1 indicating a considerable reduction of dimer stability upon electronic excitation.

Spectral signatures and structural motifs in isolated and hydrated monosaccharides: phenyl α- and β-L-fucopyranoside

The conformation and structure of phenyl-α-L-fucopyranoside (α-PhFuc), phenyl-β-L-fucopyranoside (β-PhFuc) and their singly hydrated complexes (α,β-PhFuc·H2O) isolated in a molecular beam, have been investigated by means of resonant two photon ionization (R2PI) spectroscopy and ultraviolet and infrared ion-dip spectroscopy. Conformational and structural assignments have been based on comparisons between their experimental and computed near IR spectra, calculated using density functional theory (DFT) and their relative energies, determined from ab initio (MP2) calculations. The near IR spectra of ‘free’ and hydrated α- and β-PhFuc, and many other mono- and di-saccharides, provide extremely sensitive probes of hydrogen-bonded interactions which can be finely tuned by small (or large) changes in the molecular conformation. They provide characteristic ‘signatures’ which reflect anomeric, or axial vs. equatorial differences, both revealed through comparisons between α/β-PhFuc and α/β-PhXyl; or similarities, revealed through comparisons between fucose (6-deoxy galactose) and galactose; or binding motifs, for example, ‘insertion’ vs. ‘addition’ structures in hydrated complexes. At the monosaccharide level (the first step in the carbohydrate hierarchy), these trends appear to be general. In contrast to the monohydrates of galactose (β-PhGal) and glucose (β-PhGlc), the conformations of α- and β-PhFuc are unaffected by the binding of a single water molecule though changes in the R2PI spectra of multiply hydrated α-PhFucW(n) however, may reflect a conformational transformation when n ≥ 3.