Applications of Terahertz Spectroscopy in Biosystems

Abstract

Terahertz (THz) spectroscopic investigations of condensed-phase biological samples are reviewed ranging from the simple crystalline forms of amino acids, carbohydrates and polypeptides to the more complex aqueous forms of small proteins, DNA and RNA. Vibrationally resolved studies of crystalline samples have revealed the exquisite sensitivity of THz modes to crystalline order, temperature, conformational form, peptide sequence and local solvate environment and have given unprecedented measures of the binding force constants and anharmonic character of the force fields, properties necessary to improve predictability but not readily obtainable using any other method. These studies have provided benchmark vibrational data on extended periodic structures for direct comparisons with classical (CHARMm) and quantum chemical (density functional theory) theories. For the larger amorphous and/or aqueous phase samples, the THz modes form a continuum-like absorption that arises because of the full accessibility to conformational space and/or the rapid time scale for inter-conversion in these environments. Despite severe absorption by liquid water, detailed investigations have uncovered the photo- and hydration-induced conformational flexibility of proteins, the solvent shell depth of the water/biomolecule boundary layers and the solvent reorientation dynamics occurring in these interfacial layers that occur on sub-picosecond time scales. As such, THz spectroscopy has enhanced and extended the accessibility to intermolecular forces, length- and timescales important in biological structure and activity.

Can far-IR action spectroscopy combined with BOMD simulations be conformation selective?

“…These vibrations are expected to contain detailed structural information on the overall structure and are therefore directly diagnostic to various backbone conformations. [10][11][12] Since these vibrations often extend over a large part of the peptide backbone, such delocalized modes are also expected to be important for the dynamical and flexible nature of proteins. 13 Additionally, intrinsic hydrogen bond vibrations can be directly probed in the far-IR region, 14,15 as previously shown for condensed phase systems using low-frequency FTIR spectroscopy.…”

Dissecting the THz spectrum of liquid water from first principles via correlations in time and space

“…The intermolecular vibrational modes in the frequency window from 1 THz up to about 10 THz (16,17), corresponding to ≈30-300 cm −1 , have been proven recently to be a unique tool to study the hydration dynamics around solutes (18)(19)(20)(21). Using THz laser spectroscopy, water dynamics has been shown to be influenced within an "extended dynamical hydration shell" (20) of about 6-7 Å for small solutes like carbohydrates (18) by changes in the absolute absorption intensity as probed at 2.4 THz (i.e., ≈80 cm −1 ).…”

Tunable, continuous-wave Terahertz photomixer sources and applications

“…Similar results on several small biomolecules are found by Plusquellic and coworkers. 10 Future security-related THz scanners could be operated with CW photomixing systems as proposed in refs. 172,174 When looking for molecular resonances, only those narrow frequency windows are scanned where spectral features of the species of interest appear.…”

“…6 The THz range covers the energy range for molecular rotation of polar molecules and librations of macromolecules. Because rotation spectra with many narrow characteristic lines in this frequency range represent highly selective fingerprints of molecules, [7][8][9] including (large) organic molecules, [10][11][12][13] high-resolution THz absorption spectroscopy is very appealing for chemical composition analysis, even down to the parts-per-million range. 14 In combination with imaging techniques-in particular by transmission or reflection scanningthe strong spectral sensitivity of the absorption allows for pictures that isolate certain materials or substances, 15 a property of interest to medicine, biology, and industrial production processes.…”