Pulse Radiolysis andPulse Radiolysis andSpectral ResolutionsSpectral Resolutions

Free Radical Problems in Biology and MedicineFree Radical Problems in Biology and Medicine

Spectral Resolution TechniqueSpectral Resolution Technique

Motivation for Transient ConductivityMotivation for Transient Conductivity

MotivationsMotivations

Oxidative stress• Alzheimer’s disease• Biological aging

Basic issues• Neighboring-group effects• Details of oxidative scheme

N-Acetyl-L-Methionine AmideN-Acetyl-L-Methionine Amide

STABILIZATION OF SULFURSTABILIZATION OF SULFUR RADICAL CATIONS VIA INTRAMOLECULAR SULFUR-NITROGEN AND SULFUR-OXYGEN BOND RADICAL CATIONS VIA INTRAMOLECULAR SULFUR-NITROGEN AND SULFUR-OXYGEN BOND FORMATION FORMATION

Gly-MetMet-Gly

Three-electron bondsThree-electron bonds

Scheme 1

PP

2,1* -> 1,2* origin of 480 nm absorptionin SS+ radical cations

Advantage of Radiation Chemistry:Advantage of Radiation Chemistry:Can convert all radicals to oxidizing Can convert all radicals to oxidizing

(or reducing) ones(or reducing) ones

H2O OH (G = 2.7)

H (G = 0.6)

eaq (G = 2.8)

N2O + eaq OH + OH + N2

G in units of radicals produced for every 100 eV of ionizing radiation absorbed

Strongly reducing radical

Strongly oxidizing radical

Converting reducing to oxidizing

Endo- and Exo-amidesEndo- and Exo-amides

Neighboring group participation in compounds3 but not in compounds 4?

OPTICAL ABSORPTION SPECTRA USED FOROPTICAL ABSORPTION SPECTRA USED FORSpectral ResolutionsSpectral Resolutions

Endo-amideEndo-amide

Endo-amide at pH 5Endo-amide at pH 5

Mathematics of Spectral ResolutionsMathematics of Spectral Resolutions

Aexp(j) = i i(j) ci d

i(j) is the extinction coefficient of the i-th species at wavelength j

d = optical pathlength

Knowns:

Unknowns: ci = concentration of i-th species

SSD = i|Aexp(j) i i(j) ci d|2

Minimize Sum of Squares of the Deviation by varying the ci’s

the Aexp(j) for all wavelengths j

Would like to solve for the ci’s

But problem is over determined (too much data)and there is also noisy data

Endo-amide pH 5Endo-amide pH 5 t = 650 ns t = 650 ns

SN includedno SO

Endo-amide pH 5Endo-amide pH 5t = 650 nst = 650 ns

SO includedno SN

Time-resolved conductivityTime-resolved conductivity

N-Acetyl-L-Methionine AmideN-Acetyl-L-Methionine Amide

Formation of (SS)+ and (SO)+ speciesis paralled by a net decrease

in equivalent conductivity

Time-resolved conductivityTime-resolved conductivity

N-Acetyl-L-Methionine AmideN-Acetyl-L-Methionine Amide

+OH

H+H2O

Formation of (SN) speciesis not paralled by a net change

in equivalent conductivity

Concentration profilesConcentration profiles Endo-amide at pH 5 Endo-amide at pH 5

Notes:

No SO

Only SS+ isconducting

Alternative Concentration ProfilesAlternative Concentration ProfilesEndo-amide pH 5Endo-amide pH 5

Notes:

No SN

Both SS+ andSO will conduct

ConclusionsConclusionsabout Endo-amide experimentsabout Endo-amide experiments

The expected transients account for the observed The expected transients account for the observed transient absorptions.transient absorptions.

Whether or not SN or SO is present will depend on Whether or not SN or SO is present will depend on conductivity experiments yet to be made.conductivity experiments yet to be made.

If SN, only the small amount of SSIf SN, only the small amount of SS++ will will contribute.contribute.

If SO, we expect a relatively large contribution to If SO, we expect a relatively large contribution to the conductivity at small times which decays into the conductivity at small times which decays into a smaller contribution as SO decays.a smaller contribution as SO decays.

Exo-amideExo-amide

Exo-amide pH 4Exo-amide pH 4Notes:

Same as pH 5

Namely littleNeighboringGroupParticipation

ConductivityConductivityExo-amide pH 4Exo-amide pH 4

Notes:

Net decrease inconductivity,indicates SO orSS+

Since there waslittleNeighboringGroupParticipation inabsorption, theconductive signalis probably SS+