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In this article we report experimental results on Fourier-transform infrared spectroscopy of deoxyribonucleic acid (DNA) macromolecules and related biological materials in the submillimeter range (i.e., ∼10–500 cm-1). Film samples made from commercial DNA fibers, polyadenylic acid potassium salt, and cellular agents such as the spore form of Bacillus subtillis have been prepared and measured. A broad series of measurements carried out in the low frequency region (10–50 cm-1) with a higher resolution of 0.2 cm-1 revealed fine features—multiple dielectric resonances in the submillimeter-wave spectra obtained from DNA samples. These long-wave absorption features are shown to be intrinsic properties of biological materials determined by phonon modes. The emphasis is on reproducibility of experimental spectra and on receiving reliable results. The effects of differences in sample preparation, including sample geometry, orientation, and aging are studied and separated from the phonon effects that determine the fine structure of transmission spectra. A direct comparison of spectra between different DNA samples reveals a large number of modes and a reasonable level of sequence-specific uniqueness. A theoretical study of two double helical DNA fragments has applied a normal mode analysis to predict spectra in the far infrared. Most of the modes determined by long-distance interactions are at frequencies below 220 cm-1, with the density higher than one mode per cm-1, which is approximately what was observed experimentally. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Two conformations of the retinal molecule have been studied in order to characterize the molecule's THz transmission spectra in both the ground and metastable states. When subjected to an adequate external excitation the retinal molecule can experience a change in conformation and associated THz transmission spectra. In an attempt to accomplish this characterization, the FTIR system was modified to include a simple off axis excitation source inside of the systems sample chamber. Measurements were made of the retinal molecule's THz spectra both with and without external excitation of the molecule. The results gathered were then compared with the results obtained from simulation. Data obtained from two retinal isomers reveal more spectral features at frequencies ~11 - 15 cm-1 than were predicted for these conformations. The most likely explanation for this is that the material is actually a mixture of several metastable conformations. There is correlation between simulated and measured THz spectra in the ground state at a frequency of 14 cm-1 for all-trans retinal. The strongest vibrational mode frequency predicted for the 9-cis conformation through modeling was 22 cm-1, which correlates quite well with the experimental line at 21.3 cm-1 in the ground state. When the 9-cis samples were exposed to UV illumination there was a noticeable change in the absorption spectra and this line at 21.3 cm-1 almost disappeared which can be related to the transformation of a 9-cis into a more stable all-trans retinal. The absorption spectra of all-trans retinal that is the most stable conformation showed very weak features in experimental spectra, with some of them changing under illumination. [ABSTRACT FROM PUBLISHER]

Biological macromolecules such as DNA, proteins, and polysaccharides often display unique absorptive signatures in the THz region, useful in their identification and imaging through Raman and Fourier transform transmission spectroscopy. The optoelectronic properties of nanostructure-DNA complexes immobilized on transparent, semi-rigid substrates such as polymethyl methacrylate (PMMA) have been studied. By chemically modifying the PMMA substrates with amine terminal groups and using suitable linking agents, amine terminated DNA can be localized on these substrates. THz Fourier transform transmission spectroscopy was used to detect low-frequency vibrational modes (10-25 cm-1) within single- and double-stranded DNA molecules immobilized on PMMA attached to TiO2 nanoparticles. Additionally, DNA strands end terminated with TiO2 nanoparticles are used in this study to cleave the DNA at guanine (G) rich sites due to trapping of photo-induced charge carriers from the TiO2 at these sites. Theoretical modeling of charge transport through DNA via polaron transport is discussed in detail. By examining the vibrational modes of DNA, as well as the transport of charge in DNA this study underlies potential applications involving DNA micro-arrays, DNA-based sensors, and DNA-based THz devices. [ABSTRACT FROM PUBLISHER]

In this paper, we show that periodic arrays of rectangular slots with subwavelength width provide for local electromagnetic field enhancements due to edge effects in low-frequency range, 10-25 cm-1. Periodic structures of Au, doped Si, and InSb with subwavelength thickness were studied. The half power enhancement width is ~500 nm and less around the slot edges in all cases, thereby possibly bringing terahertz (THz) sensing to the nanoscale. InSb is confirmed to offer the best results with the local power enhancements on the order of 1100 at frequency 14 cm-1. InSb and Si have large skin depths in the frequency range of interest and so the analysis of their structures was done through the Fourier expansion method of field diffracted from gratings. Au, however, has small skin depths at these frequencies compared with the thickness. Surface impedance boundary conditions were employed to model the Au structure, for which the Fourier expansion method was unsuitable owing to the huge magnitude of Au permittivity at these frequencies. The applications possibly include development of novel biosensors, with the strongly enhanced local electromagnetic fields leading to increased detection sensitivity, and monitoring biophysical processes such as DNA denaturation. [ABSTRACT FROM PUBLISHER]

We introduce here recently developed highly resolved Sub-Terahertz resonance spectroscopy of biological molecules and cells combined with molecular dynamics (MD) computational analysis as a new approach for optical visualization and quantification of the presence of microRNAs, particularly the mir-200 family, as potential biomarkers in samples from tissue of epithelial ovarian cancers for disease early detection, analysis, prognosis and treatment.METHOD: A set of samples for this study was prepared from anonymized archival formalin-fixed, paraffin-embedded ovarian epithelial tissue containing regions of invasive neoplastic cells from cases of high-histologic grade serous papillary ovarian carcinoma. Control samples were normal mucosa from fallopian tubes of patients with no known malignancy. Spectroscopic characterization of tissue samples in this study was performed using a continuous wave, frequency domain automated spectrometer operating at room temperature in the spectral region of 310-500 GHz. The spectral results were compared with molecular dynamics simulations and absorption coefficient calculations utilized to predict the absorption spectra.RESULTS: The characteristic spectroscopic features in absorption spectra, particularly the presence of absorption peaks near 13 cm-1 have been identified as cancer indicators. Tissue samples heterogeneity, reflected by diverse spectral signatures, provides additional, very specific information that may be used for identification of cancer subtypes, clinical behavior or sensitivity to specific therapies. Further work is warranted to determine if this signature can be detected in bio-fluids from ovarian cancer patients. If strongly correlated with cancer burden, it may then be investigated as a potential new biomarker for disease monitoring, and also perhaps as a biomarker for cancer screening.

Hydrogen bonds (H-bonds) in biological macromolecules are important for the molecular structure and functions. Since interactions via hydrogen bonds are weaker than covalent bonds, it can be expected that atomic movements involving H-bonds have low frequency vibrational modes. Sub-Terahertz (sub-THz) vibrational spectroscopy that combines measurements with molecular dynamics (MD) computational prediction has been demonstrated as a promising approach for biological molecule characterization. Multiple resonance absorption lines have been reported. The knowledge of relaxation times of atomic oscillations is critical for the successful application of THz spectroscopy for hydrogen bond characterization. The purpose of this work is to use atomic oscillations in the 0.35-0.7 THz range, found from molecular dynamic (MD) simulations of E.coli thioredoxin (2TRX), to study relaxation dynamics of two intra-molecular H-bonds, OH-N and OH-C. Two different complimentary techniques are used in this study, one is the analysis of the statistical distribution of relaxation time and dissipation factor values relevant to low frequency oscillations, and the second is the analysis of the autocorrelation function of low frequency quasi-periodic movements. By studying hydrogen bond atomic displacements, it was found that the atoms are involved in a number of collective oscillations, which are characterized by different relaxation time scales ranging from 2-3 ps to more than 150 ps. The existence of long lasting relaxation processes opens the possibility to directly observe and study H-bond vibrational modes in sub-THz absorption spectra of bio-molecules if measured with an appropriate spectral resolution. The results of measurements using a recently developed frequency domain spectroscopic sensor with a spectral resolution of 1 GHz confirm the MD analysis.

Sub-terahertz (THz) vibrational modes of the protein thioredoxin in a water environment were simulated using molecular dynamics (MD) in order to find the conditions needed for simulation convergence, improve the correlation between experimental and simulated absorption frequencies, and ultimately enhance the predictive capabilities of computational modeling. Thioredoxin from E. coli was used as a model molecule for protocol development and to optimize the simulation parameters. The empirically parameterized software packages Amber 8 and 10 were used in this work. Using atomic trajectories from the constant energy and volume MD simulations, thioredoxin's sub-THz vibrational spectra and absorption coefficients were calculated in a quasi-harmonic approximation. An optimal production run length ~100 ps was found, in agreement with experimental data on thioredoxin relaxation dynamics. At the same time, a new procedure was developed for averaging correlation matrices of atomic coordinates in MD simulations. In particular, the open source package ptraj was edited to improve a matrix-analyzing function. Averaging only six matrices gave much more consistent results, with absorption peak intensities exceeding those from the individual spectra and a rather good correlation between simulated vibrational frequencies and experimental data.