Theoretical and experimental considerations for interpretation of amide I bands in tissue

The vibrational spectra of molecules contain a wealth of information, if only one can find the key. Our current efforts are directed towards interpretation of spatially resolved IR, Raman and SERS spectra from our various biological and inorganic samples, and computational modeling of the spectra as aids in analysis and interpretation. We have performed hybrid Density Functional Theory/Hartree-Fock calculations with B3LYP/6-31+G(d) on glycine homopeptides with 2-9 amino acid residues formed into straight chain, alpha-helix and beta-sheet arrangements to explore some of the basic features underlying the amide I profile. The calculations give complete normal modes and intensities based on the molecular wavefunction. We discuss the general principles of carbonyl bond alignment and normal mode phase that dominate the calculated profiles. We compare computational results to experimental spectra from brain tissue of the TgCRND8 transgenic mouse model for Alzheimer disease, recorded with synchrotron-source single pixel detector and 10 mu m spatial resolution, and with a focal plane array and detector elements of 5.5 mu m. Spectra from dense core plaques imaged with both systems sometimes show radically different amide I profiles. While numerical methods can be applied to image the plaques in each case, the results illustrate the continued importance of developing instrument and target-specific parameters. (C) 2010 Elsevier B.V. All rights reserved.