SCIENTIFIC ANNALS OF “ALEXANDRU IOAN CUZA DIN IAŞI” UNIVERSITY
Tomul I, s. Biomaterials in Biophysics, Medical Physics and Ecology 2008
STRUCTURAL MODELING OF SOME ORGANIC MOLECULES
WITH BIOLOGICAL IMPLICATIONS
Elena Filip1, Claudia Nadejde2, Dorina E. Creanga2, Dana O. Dorohoi2
KEYWORDS: organic
computational approach
compound
with
nitrogen,
intermolecular
interactions,
The study of formazan like compounds is important due to their implications in oxido-reduction
reactions from certain bacterial cells. The molecular structure of some triphenylformazan
derivatives was carried out based on a molecular orbital calculation soft package HyperChem,
using a semiempirical method – PM3. The electron cloud density, the dipole moments and the
energy levels were calculated starting from the chemical structure modeling. Discussion was
carried out on the influence of substituents in the formazan derivatives structure, on the
calculated molecular parameters.
1. INTRODUCTION
Among the numerous spectral studies on solute-solvent interactions in binary
solutions [1-4], particular interest is shown to the intermolecular interactions in biological
systems [5-7] from which could be mentioned the spectral studies of Ylid solutions,
focusing on the solvatochromic behavior of various zwitterionic compounds [8-9], as well
as a variety of scientific papers on solvent effect upon the spectra of solvatochromic
probes - substances (biological molecules) whose spectra are particularly sensitive to
specific solvent properties; thus, spectroscopic parameters of solvent polarity have been
derived from solvent-sensitive standard compounds, absorbing radiation in various
spectral ranges, known as solvatochromic dyes; they are used as reference probes to
establish empirical solvent polarity scales and have a wide applicability in chemistry and
biology [10-15].
The metabolic activity of some bacterial cells is determined on the basis of
quantitative evaluation of tetrazolium reductase activity of cells. Triphenylformazan (TPF)
is an organic compound obtained after the reduction of triphenyl-tetrazolium chloride
(TTC) and it is used mainly as an indication of dehydrogenase activity. Due to oxidation
process, the colour of formazan compound is turning from white to dark red, the intensity
of its color being proportional to the enzyme activity. In a previous paper [C. Nadejde et
al., Rom. J. Phys, accepted], the behavior of the four formazan derivatives in ultraviolet
range was studied in several solvents by spectrophotometric method, revealing the types of
solute-solvent intermolecular interactions that occur in the binary solutions and evaluating
the solvent effect on the UV absorption spectra of the studied molecules. Dipole moments
in the ground and excited state were also calculated, from the recorded electron absorption
1
Univ. Al.I.Cuza, Faculty of Chemistry, Iasi 2Univ. Al.I.Cuza, Faculty of Physics, Iasi
44
E. Filip, C. Nădejde, D.E. Creangă, D.O. Dorohoi
spectra, on the basis of Bakhshiev theory. The present study aims to obtain supplementary
data on the behavior of triphenylformazans by molecular modeling of their chemical
structure [16] which allows the calculation of various electro-optical parameters of the
spectrally active molecules in their gaseous phase, the influence of the substitute groups in
their structure on the obtained molecular parameters being further discussed.
2. MATERIALS AND METHODS
Specialized soft HyperChem for quantum chemical calculation [16] based on
molecular orbital modeling – semiempirical method PM3 - was applied to determine the
electro-optical parameters in the ground state of four organic compounds with nitrogen
known as formazan derivatives: TPF1: triphenylformazan; TPF2: N-(carboxy–4 phenol)–
N’–phenyl–C–phenylformazan; TPF3: N-(nitro–4 phenyl)–N’–phenyl–C–(3 nitrophenyl)
formazan and TPF4: N-(carboxy–2 phenyl)–N’–phenyl–C–(3 nitrophenyl) formazan. The
molecules chemical structures (Fig. 1) with the specific substituent group of each
derivative compound (Table I) were considered as main informational basis for the
chemical modeling.
Fig. 1 The triphenylformazan structure.
Table I. The substituent groups corresponding for each formazan derivative.
Substitute
TPF
TPF1
R1
R2
R2’
-H
-H
-H
TPF2
-NO2
-COOH
-H
TPF3
-NO2
-NO2
-H
TPF4
-NO2
-H
-COOH
Spectrophotometric measurements were also carried out in UV-VIS range using Shimadzu
UV-1700 spectral device, in order to reveal the electronic absorption spectra (EAS). The
45
STRUCTURAL MODELING OF ORGANIC MOLECULES
EAS of binary solutions of the TPF derivatives were recorded in 10-5 M ethanol solutions
(highly transparent in the optical range), as well as in ethanol with aliquots of sulfuric
acid.
3. RESULTS AND DISCUSSION
The application of computational algorithms underlying the HyperChem
specialized soft with PM3 method, in the case of the molecules presented in (Fig. 1),
resulted in the values of several structural features such as: molecule volume and mass,
refractivity, polarizability, electron cloud density, dipole moments, energy values of
highest and lowest electronic states, as well as the corresponding spatial configurations. In
Table II, the calculated values of electro-optical parameters of the studied organic
compounds in the gaseous phase are given - in the case of the four combinations of the
two substituent groups (-NO2 and -COOH) that define the analyzed formazan derivatives.
Table II. The electro-optical parameters characteristic for each formazan derivative.
Parameter
Volume (Å3)
Refractivity (Å3)
Polarizability volume (Å3)
Mass (a.m.u.)
E HOMO (eV)
E LUMO (eV)
Dipole moment (D)
TPF1
959.19
97.25
35.93
300.36
- 8.56
- 0.89
2.15
TPF2
1091.46
111.34
40.21
389.37
- 9.01
- 1.59
6.98
TPF3
1083.17
109.89
39.74
390.36
- 9.13
- 1.69
6.91
TPF4
1053.03
109.66
40.33
389.37
- 9.12
- 1.45
8.91
It can be seen that following COOH and NO2 groups substitution, the derivatives
TPF2-4 are characterized not only by higher values of molecular mass and volume
compared to TPF1 but also by higher values of the polarizability volume and refractivity;
in the case of TPF2 and TPF4 though the mass is the same, the different positioning of the
two NO2 groups resulted in different values of the molecular volume, polariziability
volume and refractivity. Regarding the influence of the substituent upon the molecular
parameters of all four formazan derivatives, it can be seen that significantly increased
values of the two energy levels as well as of the dipole moment resulted in the TPF2-4
compared to TPF1: the EHOMO values are increased with about 5 % while remarkably
higher increasing was noticed for ELUMO (about 60-90%); the dipole moment enhanced of
3-4 times in TPF2-4 compared to TPF1 and the different positioning of NO2 group in the
case of TPF2 and TPF4 conformers is related to the dipole moment increasing with about
25 %.
In (Fig. 2) and (Table III), the spatial configurations of TPF molecules are given
together with the electron charge density values. The most important information provided
by the calculated values is related to the experimental data regarding the behavior of the
electronic absorption spectra to the protonation process. The EAS of the studied
STRUCTURAL MODELING OF ORGANIC MOLECULES
47
The EAS stability in low acid environment can be explained by mean of the
electron charge density around nitrogen atom no.4 (Fig. 2). Following the optimization of
molecules geometry, both TPF1 and TPF3 conformers exhibit stability as trans variation,
where the nitrogen atom no.4 is characterized by positive charge density values,
suggesting that the non-participant “n” electrons are involved much stronger in the
conjugation than in the case of the other two derivatives, TPF2 and respectively, TPF4, that
have the highest stability as cis arrangement; in this case, TPF2 and TPF4 exhibit negative
values of the charge density at the nitrogen atom no. 4, which probably limits by steric
effect the influence of the solvent molecules upon the central nitrogen atoms (1-2-3-4) the stability of both conformers being assured by the hydrogen bond that could occur
between the fourth nitrogen atom and the proton bound to the first central nitrogen atom.
Also, it can be noticed that the presence of –COOH group in R2 or R2’ positions, induces
an increase of the electron charge density values of the nitro groups in the formazan
derivatives.
CONCLUSION
The stability of the formazan EAS in low acid solutions can be explained on the basis of
chemical structure data provided following computational analysis. The influence of the
substituents R1, R2 and R2’ on the electro-optical molecular parameters was revealed
mainly at the level of the ELUMO values which are consistent with much stronger
stabilization of the ground electronic state in comparison to the excited state. The presence
of the substituents resulted also in considerable increasing of the dipole moment and
electron charge density values when compared to the formazan (TPF1) structure.
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