Browsing by Author "Ranatunga, R. J. K. U."

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Computational studies on the stability of nine-coordinate mixed ligand complexes formed by Zr(IV) and Hf(IV) with DOTA
(Faculty of Science, University of Kelaniya Sri Lanka, 2024) Adhikari, A. A. D. M.; Hettiarachchi, C. V.; Ranatunga, R. J. K. U.
Ultra-pure form of Zr is used as a structural material for nuclear due to its lower absorption cross-section for thermal neutron absorption cross-section, while ultra-pure form of Hf is used in nuclear reaction controlling rod due to its higher absorption cross-section for thermal neutrons. However, obtaining ultra-pure forms of Zr and Hf is difficult due to their similar chemical properties and natural coexistence. Available separation techniques are inefficient, non-environmentally friendly and costly. This project aims to develop an environmentally-friendly, economical and efficient separation method with concepts used in mixed-ligand complex formation and fractional crystallization. Here, nine coordinate mixed ligand complexes formed by Zr(IV) and Hf(IV) with octadentate primary ligand, dodecane tetraacetate (DOTA) and with different monodentate secondary ligands (L) were studied with density functional theory (DFT) calculations. In literature, the crystal structure of [Zr(DOTA)] was recorded in which recrystallization was carried out in an aqueous medium. According to our calculations, Zr(IV) and Hf(IV) can form [M(DOTA)(H2O)] in aqueous medium. Hence, it can be assumed that [M(DOTA)(H2O)] forms during dissolution of [M(DOTA)] and H2O must be leaving during the crystal formation. If a mono-dentate ligand L, has a higher affinity than H2O, towards Zr(IV) or Hf(IV), and if the nine-coordinate mixed ligand complexes forming with DOTA by Zr(IV) and Hf(IV) show a significantly high stability difference, the most stable complex (formed by either Zr(IV) or Hf(IV)) with L and DOTA can be separated through selective precipitation or fractional crystallization. According to the calculations, pyridine (py), CN- and NH3 were identified as the secondary ligands which can form nine-coordinate mixed ligand complexes with DOTA, more stable than [M(DOTA)(H2O)]. Among them, py complexes show the highest stability. Therefore, further studies were continued on amino derivatives of pyridine, since the amine group increased the nucleophilicity of pyridine and it shows that complexes formed with 4-aminopyridine (4-aminopy) and DOTA show the highest stability and the highest difference in stability for Zr(IV) and Hf(IV) complexes. Since 4-aminopy shows higher affinity towards Zr(IV) than Hf(IV), in a medium containing DOTA and a limited amount of 4-aminopy, Zr(IV) is expected to form [Zr(DOTA)(4-aminopy)] while the Hf(IV) is expected to form [Hf(DOTA)(H2O)], which can be separated through fractional crystallization or selective precipitation.
Synergism of cell penetrating peptides in adsorbing to DOPC lipid bilayers
(4th International Research Symposium on Pure and Applied Sciences, Faculty of Science, University of Kelaniya, Sri Lanka, 2019) Wijesiri, N. K.; Kumara, B. T.; Purijjala, P. W. C. M.; Ranatunga, R. J. K. U.
Cell penetrating peptides (CPPs) represent a potential breakthrough for the cellular delivery of therapeutics. CPPs are small peptidic molecules capable of translocating through cell membranes, which generally show low cytotoxicity and high transduction efficiency. Permeation mechanisms of CPPs are not fully understood, although there is evidence for both energy dependent and energy independent (passive) pathways. In this study, we performed coarse-grained molecular dynamics simulations of CPPs in the vicinity of a dioleoylphosphatidylcholine (DOPC) lipid bilayers to investigate the free energy of passive translocation, and the synergetic effects of having multiple peptides at the bilayer surface. Four different CPPs (Penetratin, C6, Transportan, K-FGF) were used in the study in order to represent cationic, amphipathic and hydrophobic peptides. Simulations were carried out in systems containing water, lipid bilayer and a single type of peptide. The MARTINI force field was used, while simulations were run under a constant pressure (1 atm) and temperature (300 K) using Berendsen control. Umbrella sampling simulations were carried out in windows 1 nm apart, spanning the relevant separation of CPPs from the bilayer membrane. Translocation free energy curves for single peptide and multi-peptide systems were generated after simulations. In the case of the cationic peptide Penetratin, the translocation profile showed a slight tendency to adsorb onto the bilayer surface, while the insertion into the membrane was highly unfavourable. This behavior is accentuated with an increased number of peptides in the system. In the case of the hydrophobic K-FGF peptide, it shows a strong adsorption for both the singular and multiple peptide systems. Moreover, the barrier for translocation is lowered substantially for the multiple peptide system, allowing for a viable route for translocation. In the case of the two amphipathic peptides, they show different behavior, where Transportan does not show any synergy, while the C6 peptides show lowering of the barrier in the presence of other peptides. The variation in the translocation energy profiles indicate that the interactions are nuanced and cannot be generalized based on the physicochemical nature of the peptide. Moreover, the synergy shown by some peptides show the possibility of multiple peptide entry pathways