Molecular recognition of carbohydrate-aromatic complexes

The specific recognition of aromatic molecules and carbohydrates is essential for many biological processes. A typical example are lectins which use the recognition of sugars and aromatic amino acids to selectively dock to cells. In this Schrödinger fellowship application it is proposed to investigate this interaction by rotational spectroscopy of model systems in the gas phase. For this, state-of-the art molecular source and beam methods and a novel broadband microwave excitation technique will be employed. The spectral signatures will allow us to determine the structures of the molecular complexes and thus also give information about the preferred conformations and the involved interaction sites, which will deepen our present understanding of molecular recognition processes. The rotational spectra of the molecules will be investigated by the emerging Chirped Pulse Fourier Transform Microwave (CP-FTMW) technique. The key innovation of this method is to excite the molecules by a chirped pulse covering a broad frequency range of for example 2 to 8 GHz in our setup. This allows to record the rotational spectra of even complex molecules in only one measurement and thus drastically shortens acquisition times and allows to compare the spectra of several molecular complexes in a reasonable time. This method is currently revolutionizing the field of rotational spectroscopy and already found several applications mainly in groups in Northern America. However the development in Europe drags behind because so far only two CP-FTMW spectrometers are operational. It is also the aim of this proposal to strengthen this type of research. As a first step of this project the gas phase, thus solvent free, rotational spectra of the proposed monosaccharides will also be measured. This will close an open gap in the available spectral data of biologically relevant molecules. The expected results will have a significant impact to astrochemistry where the identification of sugars in interstellar molecular clouds opens a window to the origin of the basic building blocks of life in the universe. Because of their biological relevance in lectin-cell interactions, it is proposed to use the sugar galactopyranose as the carbohydrate model partner. Furthermore the measurement of and a comparison with its close analogues, glucose and fucose, allow to study the importance of functional groups and stereometric properties of the carbohydrates. Models for the aromatic molecules in the recognition process will be benzene, benzoic acid, indole and the amino acid tryptophan, each showing a different degree of complexity regarding structure, functional groups and electron richness of the arene. This will clarify the roles of the different involved intermolecular forces, mainly dispersive forces and hydrogen bonds, their relative strength and their mutual influence. Finally the rotational spectra of excited states of the molecular complexes will be investigated by applying the chirped-pulse method after selectively exciting vibrational modes by applying IR laser light to the molecular complex. This will give insights into the energy redistribution and the stability of the system and hence the recognition process.

In the framework of the Schrödinger stipend rotational spectroscopy of biologically relevant molecules was pursued. The determination of the rotational transitions allows getting information about the structure and conformational properties of the molecules. Goal of the stipend was the design and the setup of a state-of-the-art microwave spectrometer and especially the extension of this technique to complexes of aromatic molecules and carbohydrates. For the spectroscopic investigation the molecules have to be mixed with a carrier gas and to be cooled and brought into the gas phase by means of supersonic expansion. This can be done via heating methods or by laser ablation, thus the removal of sample material by short, intensive laser pulses. The latter is especially suited for very fragile molecules, such as sugar molecules. The design and the implementation of this technique represented a major part of the stipend. In parallel the spectrometer was used for studies on other interesting molecules. For example aminobenzonitrile was investigating with regard to its fluorescence properties. The nuclear quadrupole coupling of the nitrogen atom allows the determination of the electronic orbital configuration at the location of the nitrogen. These information can be related to the charge transfer state dynamics upon electronic excitations. In the context of molecular recognition our work on ibuprofen should be emphasized. The inhibiting effect of this pain-relieving drug relies on the inhibition of an enzyme by a competitive recognition at the receptor. The rotational studies carried out in the framework of the stipend allowed for the determination of the energetically favored conformers and the flexibility of the functional groups of the molecule. The research made possible by the stipend laid the foundation for future microwave studies of molecules unprecedented in size and of biologically relevant molecular complexes. This will allow for new insights into the relation of structure and function of biomolecules and the involved intermolecular forces.