Structure and stability of chiral beta-tapes: a computational coarse-grained approach

We present two coarse-grained models of different levels of detail for the description of beta-sheet tapes obtained from equilibrium self-assembly of short rationally designed oligopeptides in solution. Here we only consider the case of the homopolymer oligopeptides with the identical sidegroups attached, in which the tapes have a helicoid surface with two equivalent sides. The influence of the chirality parameter on the geometrical characteristics, namely the diameter, inter-strand distance and pitch, of the tapes have been investigated. The two models are found to produceequivalent results suggesting a considerable degree of universality in conformations of the tapes.Comment: 24 pages, 5 PS figures. Accepted to J. Chem. Phy

Malarial drug targets cysteine proteases as hemoglobinases

Malaria has consistently been rated as the worst parasitic disease in the world. This disease affects an estimated 5 billion households annually. Malaria has a high mortality rate leading to distorted socio-economic development of the world at large. The major challenge pertaining to malaria is its continuous and rapid spread together with the emergence of drug resistance in Plasmodium species (vector agent of the disease). For this reason, researchers throughout the world are following new leads for possible drug targets and therefore, investigating ways of curbing the spread of the disease. Cysteine proteases have emerged as potential antimalarial chemotherapeutic targets. These particular proteases are found in all living organisms, Plasmodium cysteine proteases are known to degrade host hemoglobin during the life cycle of the parasite within the human host. The main objective of this study was to use various in silico methods to analyze the hemoglobinase function of cysteine proteases in P. falciparum and P. vivax. Falcipain-2 (FP2) of P. falciparum is the best characterized of these enzymes, it is a validated drug target. Both the three-dimensional structures of FP2 and its close homologue falcipain-3 (FP3) have been solved by the experimental technique X-ray crystallography. However, the homologue falcipain-2 (FP2’)’ and orthologues from P.vivax vivapain-2 (VP2) and vivapain-3 (VP3) have yet to be elucidated by experimental techniques. In an effort to achieve the principal goal of the study, homology models of the protein structures not already elucidated by experimental methods (FP2’, VP2 and VP3) were calculated using the well known spatial restraint program MODELLER. The derived models, FP2 and FP3 were docked to hemoglobin (their natural substrate). The protein-protein docking was done using the unbound docking program ZDOCK. The substrate-enzyme interactions were analyzed and amino acids involved in binding were observed. It is anticipated that the results obtained from the study will help focus inhibitor design for potential drugs against malaria. The residues found in both the P. falciparum and P. vivax cysteine proteases involved in hemoglobin binding have been identified and some of these are proposed to be the main focus for the design of a peptidomimetric inhibitor

Photophysical and Photocatalytic Properties of Covalent Organic Frameworks

This dissertation is most interested in how a class of materials known as covalent organic frameworks (COFs) can be designed to capture photon energy to initiate chemical reactions. Different COF designs change how long the energy is held, how it migrates, and how it is dispersed – and these differences can be used to change their performance as artificial photosynthesis platforms. Thus, it is helpful to have an informative discussion about the processes behind natural photosynthesis, that is, nature’s light harvesting strategies and photocatalytic schemes (Section 1.2) and will lead into an introduction of COFs and why they possess unique potential as artificial photosynthesis platforms (Section 1.3). Their beneficial physical qualities are complemented by understanding their electronic structures from theoretically predicted properties with specific focus on topological symmetry (Section 1.4). Synthesizing and characterizing COF systems then becomes an important consideration (Section 1.5) along with how their excited state behaviors are probed and interpreted at reaction timescales by ultrafast spectroscopic techniques (Section 1.6). Finally, a look is taken at how COF structure versatility adds unique potential in catalyst engineering (Section 1.7). The main body of this dissertation will present five main research projects that seek to test theoretical predictions, assess the impact of COF planarity, or fine tune electronic structures. To test theoretical predictions, “Tuning Photoexcited Charge Transfer in Imine-Linked Two-Dimensional Covalent Organic Frameworks, which involves exploring nodal symmetry in topologically similar COFs by varying monomers, is reported. This work has implications on charge separation characteristics of COFs which is important to retain activated catalytic sites for chemical reactions. The second project, “Impact of πConjugation Length on the Excited-State Dynamics of Star-Shaped Carbazole-π-Triazine Organic Chromophores,” doesn’t directly probe COF systems, but looks at the role of dihedral angles on intersystem crossing (ISC) rates in organic chromophores with similar star-shaped motifs like those often found in COFs. Another study on planarity is “Conjugation- and Aggregation-Directed Design of Covalent Organic Frameworks as White-Light-Emitting Diodes” that explores planar and non-planar COFs and the how this affects the deactivation of their photoexcited states. “Wavelength Dependent Excitonic Properties of Imine-Linked Covalent Organic Frameworks,” explores how subtle changes in donor-acceptor arrangements can lead to differences in excited state populations. Finally, the seminal work in this dissertation, “Imine Reversal Mediates Charge Separation and CO2 Photoreduction in Covalent Organic Frameworks,” explores the effect of the imine bond on photophysical and photocatalytic properties