1. I. Modeling the Reaction between Vinylamine and Singlet Oxygen A Semi-Empirical Molecular Orbital Computational Study

2. Singlet Oxygen u Singlet oxygen ( 1 O 2 ) is an electronically excited form of molecular oxygen. u It is short-lived (~10 -5 s), but very reactive.  Usually generated by dye-sensitization: 1 Dye ____h ____ > 1 Dye* 1 Dye* ____(isc)____ > 3 Dye* 3 Dye* + 3 O 2 __________ > 1 O 2 + 1 Dye

3. Electron Configuration of Singlet Oxygen (HOMO)

4. Typical Modes of Reaction of Singlet Oxygen

5. Reaction of 1 O 2 with Enamines u Based on product studies in more complex enamines (vinylamine is unstable and very difficult to prepare; it is modeled because it is small, and amenable to rapid calculation):

6. Modeling Singlet Oxygen Calculated  H f in kcal/mol StructureMNDOAM1MINDO/3 singlet O 2 12.2 0.7 22.8 (Experimental value is 22.5 kcal/mol)

7. Intermediates Proposed for Reaction of Singlet Oxygen with Enamines

8. Background u We had strong kinetic (substituent effect) evidence that favored rate-limiting formation of a charge- transfer complex in the photo-oxygenation (reaction with singlet oxygen) of 1-benzyl-3,4- dihydroisoquinolines, which are in equilibrium with an enamine tautomer. u We decided to model a similar mechanism for vinylamine, the simplest enamine.

9. Modeling an Interaction u An AMPAC input file was created by merging two independently optimized structures: vinylamine and singlet oxygen u Various orientations were tried u When one geometry showed attractive interaction, it was examined more closely.

10. Optimizing the Geometry u The N-O ‘bond’ length was varied u The N-O-O bond angle was varied u The C-N-O-O dihedral angle was varied u After optimizing one variable, it was fixed to optimize another; then two were fixed to optimize the third. u Finally the structure was allowed to optimize starting with the best values of the three variables.

11. Attraction between Singlet Oxygen and Vinylamine

12. Proposed Orbital Interaction

13. Optimized Geometry of the Charge-Transfer Complex u An energy minimum was found at an N-O “bond” length of 1.55 A o u The lowest energy complex was found to have an N-O- O “bond” angle of 111 o u The lowest energy complex was found to have a C-N- O-O dihedral angle of 139 o

14. Reaction Pathway Calculation: Input File to Vary Bond Length t=5000 MINDO3 vinylamine 70.0000000.000000.00000 0 0 0 61.3821010.000000.00000 1 0 0 11.090001 113.900010.000012 1 0 61.340001 124.8000 1 179.90001 2 1 3 10.999001 122.40000 179.90001 1 2 3 10.999001 120.800010.000011 2 3 11.08000 1 124.70001 0.000014 2 1 11.08000 1 121.30001 179.9000 14 2 1 81.55000 -1 111.40001 137.100011 2 4 81.130001 111.10001 138.900019 1 2 00.0000000.000000.000000 0 0 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, 2, 2.2, 2.4, 2.6, 3, 4, 6, 8, 10

15. Locating the Transition Structure u The keywords SADDLE, POWELL, and SIGMA were employed sequentially with the geometry of the reactant, a “guess” at the T.S. geometry, and the product geometry. u A FORCE calculation was done on the T.S. geometry provided by this method. u This yielded only 1 imaginary (negative) frequency, confirming the saddle point.

16. Reaction Energy Profiles: Zwitterionic Peroxide (a) and CT Complex followed by Zwitterionic Peroxide (b)

17. Conclusion u A charge-transfer complex may be competitive with direct zwitterionic peroxide formation in the reaction of singlet oxygen with enamines, particularly in those cases where more complex structures may stabilize the intermediate complex or facilitate its rearrangement.

18. II. Modeling the Quenching of Singlet Oxygen by Amines A Semi-Empirical Molecular Orbital Computational Study

19. Singlet Oxygen u Singlet oxygen ( 1 O 2 ) is an electronically excited form of molecular oxygen. u It is short-lived (~10 -6 s), but very reactive.  Usually generated by dye-sensitization: 1 Dye ____h ____ > 1 Dye* 1 Dye* ____(isc)____ > 3 Dye* 3 Dye* + 3 O 2 __________ > 1 O 2 + 1 Dye

20. Singlet Oxygen... u It is quenched efficiently by tertiary amines, especially DABCO (diazabicyclooctane): u DABCO is sterically unhindered, unlike most tertiary amines, and has a low IP...therefore it should be a good electron donor.

21. Quenching of Singlet Oxygen by Amines

22. Quenching u No chemical reaction involved...amines are unchanged u Physical quenching…rate related inversely to ionization potential of the amine u Very sensitive to steric effects in the vicinity of nitrogen u This data suggests a charge-transfer mechanism.

23. Proposed Orbital Interaction (same as for C.T. complex formation)

24. Our Approach: u Model various amines and singlet oxygen (optimized separately) in proximity to one another and look for an interaction (attraction); AMPAC/MINDO3 was used. u When an attraction is observed, examine the complex more closely to determine the optimum geometry. u Use knowledge gained from geometry of vinylamine-singlet oxygen complex.

25. Determining the Optimum N-O ‘Bond’ Distance

26. Determining the Optimum N-O-O ‘Bond’ Angle

27. Determining the Optimum N-O-O-O Dihedral Angle

28. Typical Optimum Geometry of Amine- 1 O 2 Complexes u N-O ‘bond’ length of 1.55 A o u N-O-O bond angle of 119 o u C-N-O-O dihedral angle of 180 o u Transfer of ~0.3 esu of charge from N to distal O is observed (more than in vinylamine).

29. Modeling Charge-Transfer Complexation of Amines with Singlet Oxygen N-O “bond” distance = 1.55 A o  q N = +0.35esu  q Odistal = -0.33 esu

30. Unexpected Results!

31. An Alternative Hypothesis: u Perhaps rate-limiting step is NOT formation of the charge-transfer complex, but instead is intersystem crossing (ISC) to the triplet complex: [ 1 O 2... 1 NR 3 ] ___ ISC ___ > [ 3 O 2... 3 NR 3 ] u This process can not be modeled, but can be estimated by single point calculations.

32. Considering Triplet Complex Triplet with Singlet geometry Singlet Triplet

33. Consistent with Slow ISC !

34. Acknowledgments: Financial and Technical Support u UNCW Office of Information Technology for use of the VAX computer u M.J.S. Dewar (now deceased) and Eamon F. Healy for providing a free copy of AMPAC u NSF for an ILI grant (1996) to Integrate Molecular Modeling into the Chemistry Curriculum (computers and software)

35. Acknowledgments: The Workers u Reaction of Singlet Oxygen with Vinylamine: David B. Allen and Kelly N. Taylor u Quenching of Singlet Oxygen by Amines: Charles K. Marschke, Jr., Chris A. Cottle and Noah W. Allen, III.