Recent advances in the development of ultrafast electronic circular dichroism for probing the conformational dynamics of biomolecules in solution

Abstract

Conformational dynamics of biomolecules, which can span very large time scales ranging from seconds down to femtoseconds, play a key role in their function. In this regard, the combination of the high temporal resolution of ultrafast pump-probe spectroscopy and the structural sensitivity of electronic circular dichroism (CD) spectroscopy provides an extremely promising tool to follow these dynamics with a "virtually" unlimited temporal resolution. However, although CD spectroscopy is a widely used tool in structural biology to determine the secondary structure of biomolecules in solution, transposition of these measurements to the time domain (TRCD), on the sub-picosecond time scale, remains very challenging due to their weak signals, prone to pump-induced polarization artifacts. Recent advances in laser technologies and non-linear optics however offer new perspectives for the development of femtosecond TRCD set-ups. In this review, we present recent developments in ultrafast TRCD spectroscopy. We discuss the advantages and drawbacks of the few existing functional experimental set-ups for their use to access the conformational dynamics of biomolecules at ultrashort time scales.

Artifact-free balanced detection for the measurement of circular dichroism with a sub-picosecond time resolution

“…10 -5 -10 -3 in differential absorbance) subject to pump polarization artifacts [2]. Only a few groups have developed ultrafast TRCD setups in the UV-visible range (for a review, see [3,4]). To date, only two types of detections have allowed for the comprehensive study of chiral compounds in solution [5][6][7][8][9][10][11][12][13][14][15].…”

Ab Initio Simulation of the Ultrafast Circular Dichroism Spectrum of Provitamin D Ring-Opening

“…Since the electronic CD signal depends on angular relations between the electric and magnetic transition dipole moment, it is highly sensitive to small changes in the electronic density induced by changes in the three-dimensional structure of chiral molecules. On the microsecond to second time-scale, this is a standard tool to study conformational changes in biomolecules, such as proteins and nucleic acids. , However, due to noise caused by density fluctuations of the achiral background, the overall sensitivity of CD is rather small, which makes its application for ultrafast pump–probe spectroscopy challenging. , Thanks to advances in the experimental setup, large progress has been made in recent years, leading to pump–probe TRCD spectroscopy with time-resolutions of 1 ps and below. − While the first ultrafast TRCD measurements with subpicosecond resolution were restricted to fixed wavelengths, recent advances in increasing the sensitivity also allow the broadband measurement of the TRCD. , As common in pump–probe spectroscopy, the TRCD signal can be fitted to decay functions, yielding overall relaxation rates. , However, oftentimes the TRCD contains an oscillatory fine structure, which is usually neglected in the analysis but may potentially give more information about the structural dynamics. To obtain a relationship between the oscillatory structure of the TRCD, we apply nonadiabatic excited state molecular dynamics simulations, − which have been shown to provide structural information on the photodynamics in a variety of organic systems , and are therefore well-suited to complement pump–probe experiments. − Here, we apply time-dependent density functional theory surface hopping (TDDFT-SH) molecular dynamics simulations to model the TRCD along the photoinduced ring-opening reaction of provitamin D in the gas phase.…”

“… 6 , 7 Thanks to advances in the experimental setup, large progress has been made in recent years, leading to pump–probe TRCD spectroscopy with time-resolutions of 1 ps and below. 6 − 15 While the first ultrafast TRCD measurements with subpicosecond resolution were restricted to fixed wavelengths, 12 recent advances in increasing the sensitivity also allow the broadband measurement of the TRCD. 6 , 16 As common in pump–probe spectroscopy, the TRCD signal can be fitted to decay functions, yielding overall relaxation rates.…”