MW SYSTEMATIC STUDY OF ALKALOIDS: THE DISTORTED TROPANE OF SCOPOLINE Patricia Écija Verdejo Spectroscopy Group Faculty of Science and Technology University of the Basque Country

Introduction TROPANE ALKALOIDS Solanacease Erythrocylacease tropane 2

Why are the tropane alkaloids interesting? Introduction Why are the tropane alkaloids interesting? PHARMACOLOGICAL USES ANTICHOLINERGIC Scopolamine NEUROSTIMULANTS Cocaine NEUROTRANSMISSION EXPERIMENTS Phenyltropane STRUCTURE-ACTIVITY INTERACT with other compounds NEW PHARMACOLOGICAL compounds 3

Rotational Spectroscopy Introduction Rotational Spectroscopy in Supersonic jets Tropane Alkaloids Theoretical Calculations ab initio – MP2 DFT methods – B3LYP / M062X 4

TROPANE ALKALOIDS Introduction TROPINONE X-Ray Difraction Axial 2 kJ mol-1 X-Ray Difraction Axial NMR Axial/equatorial MW Spectroscopy PCCP, 12, 6076, 2010 Kristallogr. NCS, 222, 225, 2007 A.S.J. Org. Chem., 53, 2172, 1988 EPOXYTROPANES SCOPINE 5

Experimental Set Up Scopine 97% 4-18 GHz PCCP, 12, 12486, 2010 ~0.0000001 cm-1 Resolution: 3 kHz

Decomposition Products Results Scopine Decomposition Products Scopine ---- Ne Scopine ---- H2O Reaction Product Scopine Scopine Scopoline Chem. Phys. Chem., DOI: 10.1002/cphc.201300199, 2013

Rotational Parameters of Scopoline Results Rotational Parameters of Scopoline Chem. Phys. Chem., DOI: 10.1002/cphc.201300199, 2013

Results No tunnel splitting >11.4 kJ mol-1 11.8 kJ mol-1 (MP2) Chem. Phys. Chem., DOI: 10.1002/cphc.201300199, 2013

IS LASER VAPORIZATION THE SOLUTION?

FT-MW Ablation 355 nm Nd-YAG laser ca. 2-3 mJ/pulse ~0.0000001 cm-1 Resolution: 3 kHz PCCP, 12, 12486, 2010

Results SCOPINE

Rotational Parameters of Scopine Results Rotational Parameters of Scopine

Results Tunnel splitting 6.25 (1) kJ mol-1 5.99 kJ mol-1 (MP2)

Conclusion SCOPINE SCOPOLINE SCOPINE STRUCTURAL TUNNEL SPLITTING N-Methyl group EQUATORIAL STRUCTURAL ISOMERIZATION N-Methyl group AXIAL SCOPINE C3 C6 SCOPOLINE SCOPINE Chem. Phys. Chem., DOI: 10.1002/cphc.201300199, 2013

Acknowledgements MW Spectroscopy Group Collaborators Dr. Emilio José Cocinero Montse Vallejo Estíbaliz Méndez Dr. José A. Fernández Dr. Francisco J. Basterretxea Prof. Fernando Castaño Collaborators Prof. Alberto Lesarri Prof. Jens-Uwe Grabow Prof. Walther Caminati Prof. Brooks Pate 16