Department of Chemistry

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Browsing Department of Chemistry by Subject "541.22"

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    AB INITIO and DFT computational study of Myristinin A and A structurally- related molecule
    (2019-09-20) Tshilande, Neani; Mammino, Liliana; Ghio, Caterina
    The computational study of biologically active molecules is particularly important for drug development because it provides crucial information about the properties of a molecule, which determine its biological activities. The current work considers the results of a computational study of myristinin A and a structurally-related molecule (2-(4-hydroxyphenyl)-4-[2,4,6-trihydroxy-3-(9tetradecenoyl)phenyl]-3,4-dihydro-2H-benzopyran-7-ol, here denoted as DBPO). The two compounds pertain to the class of acylphloroglucinols. They were firstly isolated from Horsfieldia amygdaline, and they exhibit a variety of biological activities, including potent anti-inflammatory activity, potent DNA-damaging activity and DNA-polymerase ß inhibition. Their molecular structures differ only by the acyl chain. Both molecules have a bulky substituent meta to the acyl group consisting of a ring system (2-(4-hydroxyphenyl)-3,4-dihydro-2H-chromen-7-ol). The DBPO molecule can exist as cis and trans isomers in relation to the double bond present in the R chain, and both isomers are here investigated individually. The OHs ortho to the acyl group can form an intramolecular hydrogen bond (referred to as the first IHB) with the sp2 O atom of the acyl group. The phenol OHs neighbouring the substituent ring system can form O–Hπ interaction with the aromatic rings of the substituent, if suitable oriented. This study focuses on the identification of the stable conformers of these molecules (considering all the possible geometries obtainable by rotations about relevant single bonds), and of the factors stabilising the conformers. Full-optimisation calculations were performed in vacuo and also in three conveniently selected solvents. The results show that the dominant stabilising factors are the first IHB and the O–Hπ interactions. Other factors which have significant influence on conformational preferences are the orientation of the ring systems of the substituent, the orientation of the OHs on substituent, the mutual orientation of the OHs of the phloroglucinol moiety and also the orientation of the acyl chain. The results in solution are consistent with the findings of other acylphloroglucinols, for instance, the narrowing of the energy gaps and the increase of the dipole moment with the increase of solvent polarity.
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    Computational study of the molecules of selected acylated phloroglucinols in vacuo and in solution
    (2012-12-19) Kabanda, Mwombeki Mwadham; Mammino, Liliana; Ghio, Caterina
    This thesis is concerned with the computational study of acylphloroglucinols - a class of derivatives of phloroglucinol characterised by the presence of a COR group - using electronic structure methods. The compounds of this class are known to be biologically active and this is the reason for the interest in their study. A preliminary investigation was conducted on the parent molecule (phloroglucinol), calculating it in vacuo and in solution and comparing it with the other hydroxybenzenes. The aim was to identify relevant characteristics, so as to be able to verify whether and to what extent these characteristics are carried on to acylphloroglucinols and maintain stabilizing influences for the whole class of compounds. The mutual orientation of the phenolic OH groups is one of these characteristics. A systematic conformational study was performed on over 140 different acylphloroglucinol structures (both model and actual), in vacuo and in three solvents differing by polarity and hydrogen bonding abilities: chloroform, acetonitrile and water. The study in water solution was complemented by the study of adducts with explicit water molecules. The results show that the most stabilising factor in all the media and for all the structures is the intramolecular hydrogen bond engaging the sp2 0 of the COR group and one of the phenolic OH ortho to it; hence, particular attention was devoted to the study of the characteristics (parameters and energy) of this hydrogen bond. The results in solution show the influence of the solvent on the molecular structures (including the characteristics of the intramolecular hydrogen bond) and the energy aspects of the solution process. The results of the study of adducts with explicit water molecules show possible preferred arrangements of water molecules around the studied acylphloroglucinol molecule, up to approximating the first solvation layer, and facilitate the interpretation of the results in water solution. Different computational methods (HF, MP2 and OFT were utilised, also depending on affordability considerations for structures of different sizes), so as to be able to compare their results and to obtain an assessment of the performance of less expensive methods (like HF), in view of their utilisation for larger acylphloroglucinol structures for which more sophisticated methods (like MP2) remain unaffordable. Comparisons show interesting similarity in the identification of trends for the most important aspects.