Dissertation (Msc Chemistry)Capsaicin is an alkaloid effective in pain management related to rheumatoid arthritis, osteoarthritis and many other pain-related diseases. However, its clinical applications are hampered by its poor solubility. Understanding its solution conformation at the molecular level will help explore its full potential as a therapeutic agent. In this study, using molecular dynamics (MD) simulation, the role of polar protic, polar aprotic and non-polar solvents on conformational behaviour of capsaicin, solvation free energy and aggregation behaviour of capsaicin are reported. In particular, molecular dynamics (MD) simulations of capsaicin in polar protic, polar aprotic and non-polar solvents viz; water, methanol (MeOH), dimethylsulfoxide (DMSO) and dichloromethane (DCM) were carried out to establish its stability and conformation. The structural orientation, conformation, stability and solubility of capsaicin are solvent dependent. Capsaicin is relatively more stable and soluble in DMSO than in DCM, MeOH and water. Capsaicin appears to be bent and extended in water, but only extended conformation is observed in other solvents. In both solvents, capsaicin is seen to be stable with trans-conformation; the measured dihedral angles ascertained that the conformational preference is due to rotation at ϕ = ± 1800. The calculated solvation free energy shows that capsaicin is more soluble in DMSO than in water. The aggregation properties of capsaicin in water and DMSO was further studied by varying the number of capsaicin monomers from 6 to 16. Capsaicin monomers in water tend to form clusters in an ordered fashion that tend to aggregate in parallel and antiparallel orientations of the phenyl ring with a bent shape of a hydrophobic tail as the monomers are increased from 6 to 16. Capsaicin is observed to form more aggregates in water than in DMSO. The findings of this dissertation offer atomistic insights into the function of solvents in capsaicin interaction and solubility. This effort is a part of a broader debate about other but equally important aspects of drug design, such as crystal structure growth and polymorphism of capsaicin. This will also attempt to give further understanding of capsaicin solubility difficulties.