Date of Award
Chemistry and Biochemistry
TMAO and urea are important osmolytes. Osmolytes help maintain cell volume with their presence inside and outside cells. Urea is used by kidney cells to neutralize strong osmotic gradients caused by excretion of hypertonic waste. Although urea is for volume- maintaining purposes, it is also known to be a strong denaturant of cellular proteins. The method by which urea destabilizes folded proteins is a debated topic. There is evidence that urea binds directly to amino acid side chains to make protein folding less thermodynamically favored. It has also been suggested that urea acts indirectly to denature proteins by destabilizing the surrounding hydrogen bonding water networks. The destabilized network allows free water molecules to interact with polar protein side chains. This indirect method is similar to the suggested method by which TMAO acts as a protein stabilizer. TMAO has been shown to counteract urea denaturation of proteins, when both are present in the cell. The mechanism for this counteraction is investigated in this project. Experimental Raman spectra of saturated urea, saturated TMAO, and saturated TMAO-urea solutions are obtained using a scanning Raman spectrometer. Theoretical calculations are performed to obtain optimized structures and simulated vibrational frequencies and Raman intensities. Experimental data shows that the addition of TMAO into a solution of saturated urea causes an 11 cm-1 blue shift of the HNH urea symmetric bending mode. This experimental shift is reproduced theoretically.
Prather, John, "Non-Covalent Ineteractions of Trimethylamine N-Oxide (TMAO) and Urea in Water" (2015). Honors Theses. 465.