Infrared Probes Based on Nitrile-Derivatized Prolines: Thermal Insulation Effect and Enhanced Dynamic Range

Abstract

Vibrational chromophores that are sensitive to local electrostatic environment are useful probes of structural variations of proteins on subnanosecond time scales, but their short vibrational lifetimes often limit their applicability. Here we explore a possibility to increase the lifetime of nitrile probes by introducing heavy atoms between the probe and protein side chains. Stereoisomers of thiocyanato-and selenocyanato-derivatized prolines, Pro-SCN and Pro-SeCN, are synthesized, and their CN stretch lifetimes in D 2 O and chloroform are measured with polarization-controlled IR pump−probe spectroscopy. The measured lifetimes of 170−330 ps for Pro-SeCN are three to four times longer than those for Pro-SCN, indicating that selenium atom is more effective than sulfur atom in blocking the intramolecular vibrational relaxation pathways of the CN stretch mode. This is further confirmed by carrying out nonequilibrium molecular dynamics simulations of the vibrational relaxation processes. Given the crucial role of the proline residue in determining protein structures, we anticipate that the Pro-SeCN probe can be an excellent site-specific probe of changes in protein local environment.

Microscopic insights into the protein-stabilizing effect of trimethylamine N-oxide (TMAO)

“…As shown (Table 1), the T 1 of the C≡N stretching vibration, consistent with previous studies (45,46), is insensitive to solvent and, thus, is not a good reporter of its local environment. This finding is consistent with the study of Cho and coworkers (47), which showed that the vibrational relaxation of a nitrile moiety attached to a large molecule in water is dominated by intramolecular pathways. In addition, the measured T 1 value (∼4 ps) indicates that in this case the lifetime-broadening contribution (∼1.3 cm −1 ) to the spectral width (10−15 cm −1 ) is small.…”

Directing the path of light-induced electron transfer at a molecular fork using vibrational excitation

“…Another important component in our system is the metal centre which acts as a vibrational energy transfer bottleneck that contributes to the localization of injected quanta of energy on either arm of the molecule. [38][39][40][41][42] Furthermore, the presence of the metal offering a two-step charge-separation process starting from a metal-to-acceptor charge transfer followed by reductive quenching from the donor is a particularly effective design strategy to achieve IR-control: 15,16,35,36 it allows the rapid population of a far-fromequilibrium gateway state where an IR pump can be introduced, and in this way perturb an otherwise symmetrical system in a spatially selective manner at a crucial crossroad where small structural and energetic fluctuations dictate the chosen electronic pathway. 43 Complementary to such excited state evolution is the ability to delay the control pulse with respect to actinic excitation, thus influencing reactivity at the decisive moments of light-induced molecular function [44][45][46][47] and circumventing the myriad of processes occurring immediately after electronic excitation, which would rapidly scramble the selectivity of mode-specific excitation.…”

On the mechanism of vibrational control of light-induced charge transfer in donor–bridge–acceptor assemblies

“…Nevertheless, the application of vibrational excitation to manipulate photo-induced reactions in the condensed phase is challenging due to the expected rapid intramolecular vibrational redistribution (IVR). The latter promptly (typically on the scale of a few femtoseconds to a few picoseconds) 17 scrambles memory of vibrational excitation as excited modes are typically strongly anharmonically coupled to other intramolecular modes, resulting in non-selective delocalized excitation 8,18 .However, under the right conditions, namely sufficient energetic and spatial separation from other intramolecular vibrations, certain modes can retain their vibrational excitation for significant periods of time [19][20][21] . ET can take place during or prior to vibrational relaxation of such modes, and it has been shown that the resulting rate of reaction can be greatly influenced by the vibrational state of the reactant 22-24 .…”

“…However, under the right conditions, namely sufficient energetic and spatial separation from other intramolecular vibrations, certain modes can retain their vibrational excitation for significant periods of time [19][20][21] . ET can take place during or prior to vibrational relaxation of such modes, and it has been shown that the resulting rate of reaction can be greatly influenced by the vibrational state of the reactant [22][23][24] .…”