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Searching the conformational space of large flexible molecules


Molecular structures in the electronic ground state can be determined via a large variety of well established techniques like microwave spectroscopy, X-ray diffraction, neutron diffraction, or NMR spectroscopy. Geometries of electronically excited states are much more difficult to obtain. In our group rotationally resolved fluorescence spectroscopy is applied to extract the rotational constants of the molecule under investigation. Further information can be gather from the spectra, like centrifugal distortion constants, orientation of the transition dipole moment, or life time of the excited state. Other complementary techniques, that also yield structural information of electronically excited states are the resonant ionization variant of rotationally resolved vibronic spectroscopy, which has been pioneered in the group of Neusser in Munich, and rotational coherence spectroscopy, introduced by Felker, and improved considerably in the group of Brutschy and Riehn in Frankfurt. A resolution of  1 part in 108 over the whole UV range is necessary to rotationally resolve the spectra of  large molecules.


The experimental setup for the rotationally resolved laser induced fluorescence (LIF) consists of a single frequency ring dye laser pumped with either with 6 W of the 514 nm line of an Ar+ laser or with 7 W of  the 515 nm line of a diode pumped cw Yb:YAG laser (ELS MonoDisk-515). The light is coupled into an external folded ring cavity for second harmonic generation (SHG). The molecular beam is formed by expanding a mostly heated sample seeded typically in 200 - 1000 mbar of argon through a 100 - 300 µm hole into the vacuum. The molecular beam machine consists of three differentially pumped vacuum chambers which are linearly connected by two skimmers (1mm and 3mm, respectively) in order to reduce the Doppler width. The molecular beam is crossed at right angles in the third chamber with the laser beam 360 mm  downstream of the nozzle. The resulting fluorescence is collected perpendicularly to the plane defined by laser and molecular beam by an imaging optics setup consisting of a concave mirror and two plano-convex lenses. The resulting Doppler width in this setup is 15 MHz (FWHM). In some experiment the Doppler width was 25 MHz, because of a slightly different arrangement of the optical system. The integrated molecular fluorescence is detected by a photo multiplier tube whose output is discriminated and digitized by a photon counter and transmitted to a PC for data recording and processing.  The relative frequency is determined with a calibrated quasi conical Fabry-Perot interferometer with a free spectral range (FSR) of about 150 MHz. The absolute frequency is determined by recording the iodine absorption spectrum and comparing the transitions to the tabulated lines.

Example: Tryptamine

Tryptamine itself, but even more its analogs serotonin (5-hydroxytryptamine) and melatonin (5-methoxy-N-acetyl-tryptamine) are known as neurotransmitters. Their conformational stabilities and preferences are of great importance for quantitative structure-activity relationships in neurotransmitter receptor interactions. Since all biological processes take place in an aqueous environment, the interaction with a defined number of solvent molecules is of great interest. The question arises how many water molecules are necessary to lock the large variety of energetically accessible conformations to the biologically active one(s). The spectrum shown below is one of the most impressive example for the power of the genetic algorithm based automated assignment. Eight overlapping isotopomers of the tryptamine B conformer have been fit simultaneously using the genetic algorithm automated technique. Further details can be found in: Schmitt, M., Böhm, M., Ratzer, C., Vu, C., Kalkman, I. and Meerts, W. L.; Structural selection by microsolvation: conformational locking of tryptamine; J. Am. Chem. Soc. 127 (2005), 10356.

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