Infrared spectroscopy modeling and quantum calculations of nucleic acids and chemical reactions
Creators: name: Qian, Cheng
Publisher: name: No Publisher Supplied
Year: 2024

description: The focus of my doctoral research in computational chemistry encompasses several key areas: modeling the infrared (IR) spectroscopy of nucleic acids, elucidating the interactions of nucleobases in molecule-metal junctions, and investigating the reaction mechanisms of fullerenes. In this thesis, I will discuss four main projects: developing vibrational transition dipole maps for nucleobases, modeling the IR spectroscopy of yeast phenylalanine transfer RNA (tRNAphe), determining adenine-gold binding configurations in single molecule conductance experiments, and revealing an inverse-electron-demand Diels-Alder (IEDDA) reaction on fullerenes.Vibrational spectroscopy serves as a powerful tool for probing the structure and dynamics of nucleic acids due to the sensitivity of specific vibrational modes, such as the carbonyl stretch modes of nucleobases, to biomolecular configurations and solvation environments. To elucidate the origin of this sensitivity, our group has developed frequency maps and coupling models enabling the modeling of the vibrational spectra of nucleic acids directly from atomistic molecular simulations. However, non-Condon effects has not been considered despite their essential role in determining the intensities of the IR absorption peaks. In collaboration with Yuanhao Liu and Prof. Sijian Wang in the Department of Statistics at Rutgers University and my group member Wenting Meng, we have developed machine learning models to describe the vibrational transition dipole moments of the base C=O and C=C stretches and elucidate the dependence of their magnitude on the nucleobase structure and solvation environment. To assess the performance of these maps, I have applied them to a variety of nucleic acid fragments and demonstrated that the transition dipole moments are highly sensitive to the solvation environments and the base pairing and stacking configurations. Combined with the frequency maps and coupling models, the transition dipole maps offer an efficient approach to model the linear and two-dimensional (2D) IR spectra of nucleic acids.In a parallel direction, I have computationally examined the structure, dynamics, and IR spectra of tRNAphe in aqueous solutions. By combining molecular dynamics (MD) simulations and spectroscopy modeling, I have computed the IR spectra for both folded and unfolded states of tRNAphe, which demonstrate excellent agreement with experiments. I have then used this computational approach to reveal the influence of cations such as Mg2+ and K+ on the spectra and stability of tRNAphe. My calculations show that the anticodon region of tRNAphe is highly sensitive to the binding of cations. Therefore, our spectroscopy modeling methods provide a useful tool to characterize the structure and dynamics of nucleic acids.As a side project, I have collaborated with Prof. Kamenetska at Boston University and carried out density function theory (DFT) calculations of single molecule–metal junction structures. My calculations demonstrate that adenine, in its deprotonated state at the imidazole moiety, bind strongly on gold tips in neutral or basic pH conditions. The molecule binds through a charge transfer reaction as the lone pairs of the imidazole nitrogen atoms, N7 and N9, donate their electrons to the gold electrodes. The pyrimidine ring nitrogen, N3, can bind concurrently and strengthen the overall metal–molecule interaction. Due to the planar geometry of adenine, the amine group does not participate in the binding to thegold tip, in contrast to most other amine-terminated molecules. My calculations also reveal the importance of interface charge transfer in stabilizing the experimentally observed binding configurations. These results lay the foundation for biosensing on gold using single molecule conductance readout.Finally, I have collaborated with Prof. Jianyuan Zhang and Yue Sun in our department to study the oxidative [4 + 2] reaction of o-phenylenediamine-derived disulfonamides with fullerene C60 and C70. To understand the unusual regioselectivity of the reactions, I have carried out DFT calculations to determine the activation energies and reaction energies of the addition reactions at various reaction sites. My results reveal that the reaction follows an IEDDA mechanism, and the [5,6]-adduct of C70 is a preferred kinetic product.