Jianbo Liu, Fangwei Liu, Wenchao Lu, Vincent Yin Department of - PowerPoint PPT Presentation

Jianbo Liu, Fangwei Liu, Wenchao Lu, Vincent Yin Department of Chemistry & Biochemistry Queens College and the Graduate Center of CUNY 2014 Fall ACS Meeting, San Francisco 08/13/2014

Biosystems • Enzymatic or nonenzymatic • Radical termination • Energy transfer from protein ‐ bound chromophores Tyr osine Met hionine Cys teine Tr y p tophan His tidine  Progression of cell death • Loss of amino acids in  Aging and diseases atmospheric aerosols  Photodynamic therapy • Chemical markers 2

Photooxidation of Amino Acids Sensitizer & Light (type II photosensitization) pH competition with radical-mediated solvent compositions Reactions (type I photosensitization) oxygen concentration 3

Our Approaches 1. GAS ‐ PHASE REACTIONS of Amino Acid Ions with Clean 1 O 2 • Distinguish intrinsic vs. external imposed properties of biomolecules • Complemented by and compared 1 O 2 + with MD simulations 2. MICROSOLVATION of Amino Acid Reactant Ions in the Gas Phase • Dynamical roles of hydrogen ‐ bounded waters 4

How We Run Reactions of His Ions with 1 O 2 2. Ions are passed into a quadrupole for 1. Generation of mass selection I k T    product B k / v His ions by ESI rel I P l reac tan t cell cell Hexapole Quadrupole Octopole ion guide 2nd quadrupole ESI source ion guide mass filter & Scattering cell mass filter & Detector ESI HV 3. Mass ‐ selected ions are guided into 4. Product ions are an octopole surrounded by a collision mass analyzed & cell, and scattered from 1 O 2 . counted. 5 Guided ‐ Ion ‐ Beam Tandem Mass Spectrometer

Generation & Detection of 1 O 2  Chemical 1 O 2 generator        21  C 1 3   2 H O Cl 2 KOH O / O 2 KCl 2 H O 2 2 2 2 2 2 Emission detection  1    Emission    3   O ( ) O ( ) hv ( 1270 nm ) 2 g 2 g Evenson Wood’s Horn MW Cavity Light Trap Optical Chopper Emission Cell TE-cooled 6 InGaAs Detector

Gas ‐ Phase Exp 1. 1 O 2 Oxidation of Protonated and Deprotonated His in the Gas Phase 7

Gas ‐ Phase Exp 1. 1 O 2 Oxidation of Protonated and Deprotonated His in the Gas Phase No oxidation products were observed. Gas-phase isolated His cannot be oxidized by 1 O 2 8

Why Is Gas ‐ Phase Isolated His Non ‐ Reactive? 9

Make Gas ‐ Phase Experiments More Biologically Relevant 10

Gas ‐ Phase Exp 2. Reactions of 1 O 2 with Hydrated HisH + (H 2 O) n and [His ‐ H] ‐ (H 2 O) n 11

Hydration effect: Suppression of Dissociative Pathways of Peroxide Intermediates by Water Cluster Dissociation 12

Dynamical Role of Water: Direct Dynamics Trajectory of [His ‐ H] ‐ (H 2 O) + 1 O 2 at E col = 0.1 eV Using Venus/Gaussian 09, w/ forces and Hessians calculated at B3LYP/4 ‐ 31G* 13

Use Hydrated Clusters to Mimic pH ‐ Dependence of Photooxidation Photooxidation of His Reaction of hydrated His in solution in the gas phase High pH Deprotonated cluster - (H 2 O) 2 + 1 O 2 [His-H] 10 - (H 2 O) + H 2 O [(His-H)OO] Cross Section (Å 2 ) 1 0.1 + (H 2 O) 2 + 1 O 2 HisH + (H 2 O) + H 2 O HisOOH 0.01 0.0 0.2 0.4 0.6 0.8 1.0 Collision Energy (eV) I. B. C. Matheson and J. Lee, Photochem. Photobiol ., 1979, 29 , 879. Gas ‐ phase solvated clusters provide a platform to elucidate intrinsic reactivity of biomolecules in vacuo. Can these results can be extrapolated to condensed phase? 14

Exp 3: On ‐ Line Reaction Monitoring of His + 1 O 2 (w/o sensitizers) in Aqueous Solution 15

UV ‐ Vis Kinetics Analysis of His + 1 O 2 in Aqueous Solution Real-time UV-Vis Monitoring 16

On ‐ Line ESI MS of His + 1 O 2 in Aqueous solution Time Profiles of Products 17

Conclusions: Non ‐ Reactivity in the Gas Phase Peroxides in Water Clusters pH ‐ Dependence in Solution  A common process: endoperoxide via [4+2] cycloaddition, and rearrange to hydroperoxide.  Hydration effect: suppression of intermediate dissociative pathways and production of stable peroxide products.  Contrasting mechanisms of protonated vs. deprotonated His lead to pH dependence in solution ��� ����� 2,5-endoperoxide ������������ 5-hydroperoxide �� �������� stable hydrated imidazole HisH + + 1 O 2 vs. ��� ����� 2,4-endoperoxide ������������ 2-hydroperoxide �� �������� hydrated imidazolone [His-H] - + 1 O 2  6  -hydoxy-2-oxo-octahydro-pyrrolo[2,3-d] imidazole-5-carboxylate + His-His cross-linking.  Biological Implications pK a (imidazole) 6.04, His exists in neutral/protonated/deprotonated forms at physiological pH 1 O 2 oxidation of the guanine moiety of DNA 18

From Gas ‐ Phase to Solution ‐ Phase Dynamics Acknowledgements Master’s Students Ph.D. Students Undergraduate Students Yigang Fang Rifat Emre Vicnent Yin Fangwei Liu Yun Chen Wenchao Lu Collaborators Bill Hase (Texas Tech Univ) Al Viggiano (AFRL) 19