1. Flaminia Rondino CNR – IMIP Università “La Sapienza" Molecular recognition in complexes of chiral aromatic molecules with water, amines and alchools: a mass resolved R2PI spectroscopic study. - Betul Yurdumakan et al. Chem Comm., 2005, 3799 - Pavel Hobza et al., Phys. Chem. Chem. Phys., 2007, 9, 5291 1 st Italian Workshop on UltraViolet Techniques and Applications. WUTA08

2. Non covalent interactions. The nature has been forced to create weaker bonds to represent the basic machinery for the very existence of life. Several molecules involved in the processes of living systems are linked through non covalent interactions. The molecular aggregates are much more flexible than chemically bonded systems, because non covalent interactions are weaker than covalent ones. Non-Covalent Interactions Van der Waals interactions Electrostatic interactions Hydrogen bond Steric repulsion

3. Non covalent interactions in living systems Non-Covalent Interactions Molecular recognition in cells: enzime - receptor interaction drug - receptor interaction … Base pairing in nucleic acids Secondary structure of the proteins -sheet -helix

4. S-Penicillammine Antiartritic R-Penicillammine Toxic Chiral recognition, or the ability of a chiral probe to differentiate between the two enantiomers of a chiral molecule, is very important in biochemistry and organic synthesis. Most of the processes related to the interaction of a chiral ligand, such as a drug, with enzymes or protein receptors are characterized by marked enantioselectivity. Chiral Recognition

5. Molecular and chiral recognition in gas phase Isolated complexes in gas phase Ideal system to investigate at a microscopic level the specific interactions which drive the molecular recognition processes the results are directly comparable with advanced theoretical calculations. connection between the microscopic processes in molecular clusters and the architecture and function of biomolecules in living matter DIASTEREOMERIC CLUSTERS PARTNER MOLECULE R and S CONFIGURATION CHROMOPHORE MOLECULE FIXED CONFIGURATION

6. REMPI – Experimental Apparatus REMPI/TOF: Resonant Enhanced Multi-Photon Ionization in supersonic beam coupled with time of flight mass spectrometer (TOF/MS ). Chromophore Partner

7. REMPI – 1c e 2cR2PI m/e  (cm -1 ) ‏ C = chromophore    (cm -1 ) ‏ MASS SPECTRUM IONIZATION THRESHOLD ABSORPTION SPECTRUM 1

8. REMPI – 1c and 2cR2PI C = chromophore L = guest molecule D 0 " = AE (C + ) - IP (C) ‏ D 0 + = AE (C + ) - IP (C. L) ‏ D 0 ' = D 0 " -  Resonant Enhanced Multi-Photon Ionization laser spectroscopy, coupled with Time of Flight Mass Spectrometry (MS-TOF), of neutral clusters produced in supersonic beam. Vibronic spectra Binding energies Photo-fragmentation thresholds

9. REMPI – The chromophores ionization potentials ~ 10 eV intense   * electronic transitions ~ 5 eV Chiral aromatic molecules (R)-1-phenylethanol OH (R)-1- indanol (R)- 1-tetralol H CF 3 HO OH (R)-1-phenyl-1-propanol (1S,2S)-methyl pseudoephedrine p,m,o-fluoro-secbutyl-benzene H C2H5C2H5 HO CH 3 H (R)-1-phenyl-2,2,2- trifluoroethanol FE R PRPR

10. Chiral partners in the cluster with FE R. - Ethero alcohols Chiral Partners - Alcohols - Amines - Ethers OH (R/S) 2-butanol NH 2 (R/S) 2- butylamine O tetrahydrofuran (R/S) 3-Hydroxy-Tetrahydrofuran O OH

11. 1cR2PI spectrum of P R H C2H5C2H5 HO (R)-1-phenyl-1-propanol (P R ) ‏ B3LYP/6-31G**-calculated structures E rel =0.0 KJmol -1 E rel =2.5 KJmol -1 B A C A B C A B E rel =1,7 KJmol -1 C 0 0 0 (A)= 37577 cm -1 0 0 0 (B)= 37618 cm -1 0 0 0 (C)= 37624 cm -1

12. Electronic shift of the S 1  S 0 transition When a chromophore C interacts with a molecule L, a decrease or an increase for the S 1  S 0 transition energy can be observed.  < 0 Red Shift  > 0 Blue Shift C* C (CL)* (CL) ‏ (CL’)* (CL’) ‏ S0S0 S1S1 intra and intermolecular hydrogen bond interaction OH --- interaction dispersion interaction Red Shift  In the interaction of C with L, the excited state is more stabilized than the ground state Blue Shift  In the interaction of C with L, the excited state is less stabilized than the ground state

13. Cluster of P R with water ground state B3LYP/6-31G**-calculated structure 1cR2PI spectrum of a mixture of P R and water

14. Cluster of P R with 2-butanol (B R/S ) ‏ THE DIFFERENT SPECTRAL SHIFTS LET TO DISCRIMINATE THE HOMOCHIRAL AND HETEROCHIRAL CLUSTER OH (R/S)-2-butanol 1cR2PI spectra of a mixture of P R and B R or B S HOMOCHIRAL CLUSTER the chromophore P and the partner B have the same chiral configuration HETEROCHIRAL CLUSTER the chromophore P and the partner B have different chiral configuration

15. Photodissociation and photoreaction L ∙∙∙∙∙ + H HO C2H5C2H5 [P R ] + + L hh [P R · L] [P R -C 2 H 5 · L ] + + C 2 H 5 [P R -C 2 H 5 ] + + C 2 H 5 + L [P R · L ] hh [P R · L ] +

16. D0”D0” D0+D0+ ionization threshold of [P R · B S ] Dissociative ionization threshold of [P R · B S ] ionization threshold of bare P R Chem. Eur. J. 2000, 6, No. 6 D 0 " = AE (C + ) - IP (C) ‏ D 0 + = AE (C + ) - IP (C. L) ‏ D 0 ' = D 0 " -  OH (R/S)-2-butanol Cluster of P R with 2-butanol (B R/S ) ‏

17. Binding energies of neutral, excited and ionized clusters (R)-2-pentanol PRPR 6,0 ± 0.4 (S)-2-pentanol PRPR (R)-2-butanol PRPR 4,7 ± 0.4 (S)-2-butanol PRPR D 0 ” Experimental binding energy difference KJ/mol Solvent moleculeChromophore We measured the binding energies for benzyl alcohol derivatives clustered with chiral alcohols and amines, and found that the homochiral clusters are more stable than the heterochiral ones in the ground, excited and ionic state.

18. Photodissociation and photoreaction L ∙∙∙∙∙ + H HO C2H5C2H5 [P R ] + + L h  [P R ·L] [P R -C 2 H 5 · L ] + + C 2 H 5 [P R -C 2 H 5 ] + + C 2 H 5 + L [P R · L ] h  [P R · L ] +

19. Photofragmentation of P R ion [P R ][P R ]* h + H HO C2H5C2H5 [P R ] + h [P R -C 2 H 5 ] + + C 2 H 5 PR+PR+ [P R -C 2 H 5 ] + 7500 cm -1 Phys.Chem.Chem.Phys 2004 Angew. Chem. 43 1868 2004

20. Photofragmentation of P R ion [P R ][P R ]* h + H HO C2H5C2H5 [P R ] + h [P R -C 2 H 5 ] + + C 2 H 5

21. Fragmentation in clusters 4255 ± 50 [P R · Th S () ] 4129 ± 50 [P R · Th S () ] 4436 ± 50 [P R · Th S () ] 4178 ± 50 [P R · Th R () ] 4058 ± 50 [P R · Th R () ] 4515 ± 50 [P R · Th R () ] 740 ± 50[P R · Bd ss ] 1140 ± 50[P R · Bd RR ] 3500 ± 50[P R · H 2 O] 7500 ± 50PRPR E exp/th (cm -1 ) ‏ The solvation of P R causes a decrease of the fragmentation barrier for the ethyl loss, due to the stabilization of the positive charge on the chiral C of the P R

22. Fragmentation in clusters. 4255 ± 50 [P R · Th S () ] 4129 ± 50 [P R · Th S () ] 4436 ± 50 [P R · Th S () ] 4178 ± 50 [P R · Th R () ] 4058 ± 50 [P R · Th R () ] 4515 ± 50 [P R · Th R () ] 740 ± 50[P R · Bd ss ] 1140 ± 50[P R · Bd RR ] 3500 ± 50[P R · H 2 O] 7500 ± 50PRPR E exp/th (cm -1 ) ‏ Monosolvation of the [Pr] + radical cation strongly reduces the activation barrier of its C  -C  bond cleavage and markedly depend on the specific configuration and conformation of the chiral solvent molecule.

23. (R)-1-phenylethanol H CF 3 HO p,m,o-fluoro-secbutil-benzene HO CH 3 H p,m,o-fluoro- (R)- 1-phenylethanol FE R ionization potentials ~ 10 eV intense   * electronic transitions ~ 5 eV Chiral aromatic molecules The fluorinated chromophores The insertion of fluorine into organic molecules causes important changes of their physico-chemical properties, chemical reactivity and biological activity in comparison to the non- fluorinated analogues. Furthermore, fluorinated compounds, in which fluorine replaces hydrogen, have great impact on our daily life, as they are drugs, inhibitors and substrates of enzymatic reactions... (R)-1-phenyl-2,2,2-trifluoroethanol

24. Clusters of FE R with the two enantiomers of 3-hydroxy-tetrahydrofuran. 3 mains bands are present in each cluster spectrum R S Heterochiral cluster Homochiral cluster

25. R S Heterochiral cluster - HF Homochiral cluster - HF Clusters of FER with the two enantiomers of 3-hydroxy-tetrahydrofuran.

26. HF loss reaction in the cluster h 1 [FE R -HF · Th R/S ] + + HF [FE R · Th R/S ] + h 1 [FE R · Th R/S ] * FE R + L FF F H HO HF loss O R’ R +

27. HF loss reaction in the cluster h 1 [FE R -HF · Th R/S ] + + HF [FE R · Th R/S ] + h 1 [FE R · Th R/S ] * FE R + Th R/S [FE R Th R/S ] mass=264 [FE R (Th R/S -HF)] mass=244 Eterochiral cluster Homochiral cluster

28. Intracluster reactions with different solvents HF elimination -H2OH2O REACTIONSOLVENT O OH O

29. Intracluster reactions with different solvents HF elimination 199 206 HF elimination196 HF elimination195 -165H2OH2O REACTION PA (Kcal/mol) ‏ SOLVENT O OH O

30. Intracluster reactions with different solvents 8.9 dissociative electron transfer 215CH 3 NH 2 dissociative electron transfer HF elimination - REACTION 8.5222 9.8 199 206 9.4196 9.9195 12.6165H2OH2O IP (eV) ‏ PA (Kcal/mol) ‏ SOLVENT O OH O NH 2 IP(FE R ) EXP = 9.2 eV J. Phys. Chem. A 2007, 111, 12559-12563

31. The REMPI-TOF technique is a powerful tool to enantiodiscriminate molecules through their complexation with a suitable chiral selector (  absorption spectrum, binding energies in the ground, excited and ionic state). The gas phase reactivity of a chiral species can be deeply affected by asymmetric microsolvation (  photo fragmentation, effect on the HF elimination, barrier aromatic substitution). Conclusions These observations open the way to a understanding of the role of non covalent interactions in reactive processes and transfer mechanism in the living system.

32. Prof. Anna Giardini Dr. Lorenzo Avaldi Prof. Maurizio Speranza Dr. Susanna Piccirillo Dr. Alessandra Paladini Dr. Daniele Catone Dr. Mauro Satta Dr. G. Cattenacci Acknowledgments

34. (R)-1-phenyl-2,2,2-trifluoroethanol (FE R ) ‏ Ab initio B3LYP/6-31G** theoretical calculations

35. Cluster of FE R with water Ab initio B3LYP/6-31G** theoretical calculations

36. Potential Energy Surface PM3

37. C-C bond distance energy OH C2H5C2H5 + H solv OH H + C2H5C2H5 solv OH H C2H5C2H5 + solv solv=none solv=W solv=Bd RR solv=H 2 O (proton affinity=165 kcal mol -1 ) solv=2,3-butanediols (proton affinity=206 kcal mol -1 )