Deducing the conformational space for an octa-proline helix

Abstract

A molecular dyad, PY-P₈-PER, comprising a proline octamer sandwiched between pyrene and perylene terminals has been synthesized in order to address the dynamics of electronic energy transfer (EET) along the oligo-proline chain. A simple pyrene-based control compound equipped with a bis-proline attachment serves as a reference for spectroscopic studies. The N–H NMR signal at the terminal pyrene allows distinction between cis and trans amides and, although the crystal structure for the control has the trans conformation, temperature-dependent NMR studies provide clear evidence for trans/cis isomerisation in D₆-DMSO. Polar solvents tend to stabilise the trans structure for the pyrene amide group, even for longer oligo-proline units. Circular dichroism shows that the proline spacer for PY-P₈-PER exists mainly in the all-trans geometry in methanol. Preferential excitation of the pyrene chromophore is possible at wavelengths in the 320–350 nm range and, for the dyad, is followed by efficacious EET to the perylene emitter. The probability for intramolecular EET, obtained from analysis of steady-state spectroscopic data, is ca. 80–90% in solvents of disparate polarity. Comparison with the Förster critical distance suggests the terminals are ca. 18 Å apart. Time-resolved fluorescence spectroscopy, in conjunction with DFT calculations, indicates the dyad exists as a handful of conformers displaying a narrow range of EET rates. Optimisation of a distributive model allows accurate simulation of the EET dynamics in terms of reasonable structures based on isomerisation of certain amide groups.