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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. August 2005, Volume 4, Number 8, 591-602 |
Molecular Structure and Reactive Sites of Substituted Di-(4-hydroxycoumarin)s
Derived from DFT Calculations
Natasha Trendafilova and Tzvetan Mihaylov
Internet Electron. J. Mol. Des. 2005, 4, 591-602
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Abstract:
Substituted di-(4-hydroxycoumarin)s have distinct biological
properties. The activity of this class of compound is closely related
to their stereochemistry. To reveal the specific character of the
structure-activity relationship of di-(4-hydroxycoumarin)
derivatives, their molecular and electronic structures have to be
known in details. Therefore, we present accurate DFT calculations
of benzyl and pyridyl substituted di-(4-hydroxycoumarin)s.
Electron density distribution, molecular electrostatic potential,
hardness, electrophilicity index and reactive sites of the
compounds are also calculated and discussed. The calculations
were performed with DFT(B3LYP) method. Different basis sets
were tested in the course of the calculations: 6-31G*, 6-31+G**
and 6-311G*. According to the calculated molecular electrostatic
potential and Fukui functions, the most probable reactive sites for
electrophilic attack and hydrogen bonds were predicted. All the
species studied showed two O-H…O asymmetrical intramolecular
hydrogen bonds. The HB strengths were evaluated in the frame of
the classical method as well as using the rotational barrier method.
The effects of the methylene substituent (benzyl and pyridyl) on
the HB strengths and on the electron density distribution in the
coumarin fragments were evaluated. Steric, electronic and
electrostatic factors (through the oxygens charge changes) were
found to be responsible for the HB asymmetry in the compounds
studied. The highest electronegativity, hardness and
electrophilicity values were found for the para and the lowest ones for
the ortho isomer, respectively. The Fukui functions showed that the
carbonyl oxygen atoms are the most probable sites for electrophilic
attack, whereas the MEP calculations indicate that the most
suitable atomic site for electrophilic attack is the nitrogen.
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