Molecular Recognition and Interaction between Uracil and Urea in Solid-State Studied by Terahertz Time-Domain Spectroscopy

Abstract

Using terahertz time-domain spectroscopy characterization, we observe that urea is able to recognize and interact with uracil efficiently even in the solid phase without involving water or solvents. A cocrystal configuration linked by a pair of hydrogen bonds between uracil and urea was formed. The terahertz absorption spectrum of the cocrystal shows a distinct new absorption at 0.8 THz (26.7 cm(-1)), which originates from the intermolecular hydrogen bonding. Both mechanical milling and heating can accelerate the reaction efficiently. Density functional theory was adopted to simulate the vibrational modes of the cocrystal, and the results agree well with the experimental observation. Multiple techniques, including powder X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy, were performed to investigate the reaction process, and they presented supportive evidence. This work enables in-depth understanding of recognition and interaction of urea with nucleobases and comprehension of the denaturation related to RNA. We also demonstrate that terahertz spectroscopy is an effective and alternative tool for online measurement and quality control in pharmaceutical and chemical industries.

Combined X-ray Crystallographic, IR/Raman Spectroscopic, and Periodic DFT Investigations of New Multicomponent Crystalline Forms of Anthelmintic Drugs: A Case Study of Carbendazim Maleate

“…We focus on reproducing the frequencies, as well as IR and Raman activities, in the low-frequency spectral range. It is currently being intensively studied [29,65,66], since various intermolecular vibrations can be observed in it, in particular, because of the presence of intermolecular H-bonds [36,[67][68][69]. The double harmonic approximation provides a reasonable description of the IR/Raman spectra of organic crystals in the low-frequency spectral range [29,30,70,71].…”

The Necessity of Periodic Boundary Conditions for the Accurate Calculation of Crystalline Terahertz Spectra

“…95,96 However, many recent studies have used ab initio gas-phase simulations to assign experimental condensed phase terahertz spectra, with varying levels of apparent success. [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] It is important to note that in almost all of these cases the discussed 'agreement' with experiment is largely based upon the position of calculated vibrational transitions, with little focus placed upon the accuracy of the predicted mode-types -critical for gaining deeper insight into the way terahertz motions influence bulk material properties, for example. Therefore, this work aims to asses how gas-phase simulations reproduce terahertz spectra, as well as predicting the corresponding vibrational mode-types.…”

Raman and Terahertz Spectroscopic Investigation of Cocrystal Formation Involving Antibiotic Nitrofurantoin Drug and Coformer 4-aminobenzoic Acid

“…These established techniques are sometimes time-consuming or lack specific structural information about crystals and/or molecules-especially the effect from the intra-molecular and weak inter-molecular interactions. Vibrational spectroscopic techniques include mid-infrared, Raman, and terahertz (THz) spectroscopy, which have already been successfully used to explain cocrystallization of different solid-state pharmaceuticals [14,[24][25][26][27][28][29][30][31][32][33][34][35][36][37]. It is of great importance to use such specific techniques to probe the cocrystal characteristics in order to directly obtain the structural and/or dynamic information at the molecular level to better know the structural information of the specific cocrystal and also its formation mechanism [24,[26][27][28]31,32,[35][36][37][38].…”