1. SURVEYING THE HYDROGEN BONDING LANDSCAPE OF AN ACHIRAL, α-AMINO ACID: CONFORMATION SPECIFIC IR AND UV SPECTROSCOPY OF 2-AMINOISOBUTYRIC ACID TD02 Joseph R. Gord, Daniel M. Hewett, Matthew A. Kubasik, and Timothy S. Zwier

2. Introduction  -aminoisobutyric Acid (Aib) n forms 3 10 helices – (i → i+3) – 3 residues/turn  and  angles are typically -60º and -30º, respectively How does the choice for capping agent influence structure? How does length influence structure? φψ (n) Timothy Zeko; Steven F. Hannigan; Timothy Jacisin; Matthew J. Guberman-Pfeffer; Eric R. Falcone; Melissa J. Guildford; Christopher Szabo; Kathryn E. Cole; Jessica Placido; Erin Daly; Matthew A. Kubasik; J. Phys. Chem. B 2014, 118, 58-68. DOI: 10.1021/jp408818g Copyright © 2013 American Chemical Society

3. The Big Picture

4. Methods s0s0 snsn Ion R2PIIR-UV HB s0s0 snsn Ion 200 ns s0s0 snsn Ion RIDIRS 200 ns S0S0 A A A A B B B B C C C C A B C A B C A B C CAB

5. Z-Aib-OH (Major) Molecule Relative Energy (kJ/mol) 13.51 24.47 C5, g+0.00 43.52 58.81 76.00 C5, anti2.80 Z-Aib-OH C5, g+Z-Aib-OH C5, anti A B A = 37602 cm -1 B = 37576 cm -1 * * Z-Aib-OH C5, g+ Z-Aib-OH C5, anti C5 Free OH

6. Possible Assignments (Minor) Molecule Relative Energy (kJ/mol) 13.51 24.47 C5, g+0.00 43.52 C5*,8.81 76.00 C5, anti2.80 OH-1 OH-2 Conf A OH-4 Z-Aib-OH C5 OH-7 (Conf A) OH-2 OH-1 OH-4OH-7Z-Aib-OH C5

7. Z-Aib-OH vs Z-Gly-OH Published in: Jacob C. Dean; Evan G. Buchanan; Timothy S. Zwier; J. Am. Chem. Soc. 2012, 134, 17186-17201. DOI: 10.1021/ja306652c Copyright © 2012 American Chemical Society A B Z-Aib-OH C5, g+ [0.0 kJ/mol] A = 37602 cm -1 B = 37576 cm -1 A = 37601 cm -1 B = 37598 cm -1 Z-Aib-OH (2) [ 4.5 kJ/mol] MoleculeRingφψBond Type Z-Aib-OH C5, g+83-180 C5 Z-Aib-OH C5, anti180 -180C5 Z-Gly-OH C5, g--84179180C5

8. Z-(Aib) 2 -OH 3434 cm -1 3272 cm -1 3427 cm -1 3574 cm -1 * * * * Z-(Aib) 2 -OH C5, g- Free OH Z-(Aib) 2 -OH C5, g- [+ 4.27] Free NH C5 NH Molecule Relative Energies (kJ/mol) OH OrientationPhenylPhiPsiPhi2Psi2 Bond Distance Z-(Aib) 2 -OH C5, g-4.27Cis -785832172-178 2.13 Z-(Aib) 2 -OH g-7.18Cis-7055-140-49-42 Z-(Aib) 2 -OH C7, g-12.7 Cis-7677-36-17033 2.02 Z-(Aib) 2 -OH C7, g+4.38 Trans 80-60-34-6856 1.7 Z-(Aib) 2 -OH C7/C7, g-7.14 Trans -7172-64-71531.7, 1.9 Z-(Aib) 2 -OH C10, g+0 Trans74-58-31-60-241.9

9. Additional Assignments C7 C7 NH C5 C10 Z-(Aib) 2 -OH g- Z-(Aib) 2 -OH C5/7, g- Z-(Aib) 2 -OH C7, g+ Z-(Aib) 2 -OH C7/C7, g- Z-(Aib) 2 -OH C10, g+

10. Z-(Aib) 2 -OMe Z-(Aib) 2 -OMe C5/7, g- [+ 4.31] * 3418 cm -1 3342 cm -1 3407 cm -1 Molecule Relative Energies (kJ/mol) StructureBond MembersPhenylPhiPsiPhi 2 Psi 2 Bond Length C5, g- 1.74C5NH···O=C-766324-541412.3 C5/7, g- 4.31C5, C7 NH···O=C, NH···O=C -7772-70-180-1792.1, 2.2 C5, g- 2.60C5NH···O=C-86-64-31-174-1762.14 Stack, g+ 6.88Stack? 846887-51-38 17 9.67? 70-49133-50-44 Z-(Aib) 2 -OMe C5, g- [+ 2.60] * * * C7 + C5 NH Free C5

11. Z-(Aib) 2 -OtBu Z-(Aib) 2 -OtBu C5, g+ [+ 3.53] Z-(Aib) 2 -OtBu C5/7, g- [+ 10.3] Molecule Relative Energies (kJ/mol) StructurePhenylPhiPsiPhi 2 Psi 2 C5, g+3.53 C581-61-34-177-176 C5/7, g-10.3 C5/7-8374-64180-174 C7 + C5 NH Free C5

12. Conclusions Z-Aib-OH vs Z-Gly-OH – Side chain seems to have very little influence on the electronic spectrum With only 2 Aib residues, there is not enough H- bonding potential to see helix formation – Dihedral angles do appear to indicate the beginning of helix formation OH vs OMe vs OtBu – Caps have significant influence on the hydrogen bonding (OH) – OtBu proved very difficult to work with There is still much to be learned!

13. Future Work ?

14. Acknowledgements Prof. Timothy S. Zwier Prof. Matthew A. Kubasik Prof. Hyuk Kang Dr. Jacob C. Dean Zwier Group Members – Daniel Hewett Additional Talks: TD01, TD02, TD05, TG08, TG11, WI10, RB03, FD06, FE12