Computational chemistry for complex systems : open-shell molecules to conjugated organic materials

Abstract

This thesis focuses on two different, but equally challenging, areas of computational chemistry: transition metal organic molecule interactions and parameterisation of organic conjugated polymers for molecular dynamics simulations. The metal-binding properties are important for understanding of biomolecular action of type 2 diabetes drug and development of novel protocols for redox calculations of copper systems. In this area the challenge is mainly related to the complex electronic structure of the open-shell transition metals. The main challenges for the parameterisation of conjugated polymers are due to the size of the studied systems, their conjugated nature and inclusion of environment. Metal-binding properties as well as electronic structures of copper complexes of type 2 diabetes drug metformin (Metf) and other similar, but often inactive, compounds were examined using DFT method. It was found that for neutral compounds it is not possible to explain the differences in their biological effects solely by examining the copper-binding properties. Further, the proposed mechanism potentially explaining the difference in the biomolecular mode of action involves a possible deprotonation of biguanide and Metf compounds under higher mitochondrial pH which would lead to formation of more stable copper complexes and potentially affecting the mitochondrial copper homeostasis. In addition, redox properties of copper-biguanide complexes could interfere with the sensitive redox chemistry or interact with important metalloproteins in the mitochondria. Understanding the copper-binding properties is also important for a systematic development and testing of computational protocols for calculations of reduction potentials of copper complexes. Copper macrocyclic complexes previously used as model systems for redox-active metalloenzymes and for which experimentally determined redox potentials are available were used as model systems. First adequacy of using single reference methods such as DFT was examined for these systems and then various DFT functionals and basis sets were tested in order to develop accurate redox potential protocol. It was shown that good relative cor-relations were obtained for several functionals while the best absolute agreement was obtained with either the M06/cc-pVTZ functional with the SMD or either M06L or TPSSTPSS functional with cc-pVTZ basis set and the PCM solvation model. Organic conjugated polymers have a great potential due to their application in organic optoelectronics. Various wavefunction and DFT methods are utilized in order to systematically develop parameterisation scheme that can be used to derive selected force-field parameters such as torsional potentials between monomer units that are critical for these systems and partial charges. Moreover, critical points of such a parameterisation are addressed in order to obtain accurate MD simulations that could provide valuable insight into material morphology and conformation that affect their optical properties and conductivity. It was shown that a two step approach of geometry optimisation with CAM-B3LYP/631G* and single point (SP) energy scan with CAM-B3LYP/cc-pVTZ is able to yield accurate dihedral potentials in agreement with the potentials calculated using higher level methods such as MP2 and CBS limit CCSD(T). Further, investigating partial charge distribution for increasing backbone length of fluorene and thiophene it has been found that it is possible to obtain a three residue model of converged charge distributions using the RESP scheme. The three partial charge residues can be then used to build and simulate much longer polymers without the need to re-parametrize charge distributions. In the case of side-chains, it was found that it is not possible to obtain converged charge sets for sidechain lengths of up to 10 carbons due to the strong asymmetry between the side-chain ends. Initial validation of derived force-field parameters performed by simulations of 32mers of fluorene with octyl side-chains (PF8) and thiophene with hexyl side-chains (P3HT) in chloroform and calculation of persistence lengths and end-to-end lengths showed close correspondence to experimentally obtained values.