Molecular structure and
energetic features of N-containing heterocyclic vitamins
Authors: Nizhenkovska I.V. MD, Afanasenko O.V. PhD,
Bogomolets National Medical University, Kiev, Ukraine
According
to Lehrman Brothers Pharmaceutical Research only one out of ten thousand
synthesized substances becomes a medicine. It is a time consuming and costly
process. The process from synthesis till market introduction takes 10-15 years
and costs about 1 billion dollars. [1] Nowadays molecular pharmacology and
quantum chemistry are being developed, new computer modeling programs are
implemented in order to predict synthesis pathways as well as biological and
pharmacological activity of new medicines. [2] This process is called targeted
synthesis (virtual screening, QSAR- analysis, in silico research, computer
modeling and forecasting, molecular docking) and it allows the forecasting of synthesized
substances activity, in order to chose the most effective ones and to evaluate
possible molecular mechanisms of their actions. [3]
Objective – to calculate
energetic and structural parameters of N-containing heterocyclic vitamins to
assess their molecular structure and possible biological activity.
Subjects – natural origin
substances: thiamine, pyridoxine, riboflavin.
The
thiamine molecule atoms charges were calculated. The most electron density was
localized on nitrogen (-0,247; -0,213; -0,219; -0,337) and oxygen (-0,331) atoms, but the density on sulfur atom was minor (0,174). Therefore there is nucleophilic
as well as electrophilic property residing in thiamine molecule. This allows
thiamine molecule to interact with different reactive biosubstrat molecular
centers. Dipole thiamine molecular moment (1,78
Debye unit) is very high which evidences its polarity, hydrophily
and solubility in water. While calculations of boundary highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy it is
evidenced that LUMO in thiamine molecule covers pyrimidine cycle. HOMO is
localized on thiazole atom and minor on carbon atom bonded with hydro
compounds. So mentioned atom compounds will determine reactivity of thiamine
molecule under the interaction with diverse ligands.
Pyridoxine molecule
contains the most negatively charged oxygen atoms (-0,316;
-0,311; -0,239) and nitrogen atoms (-0,111). Carbon atoms, bonded with electro negative oxygen atoms, carry positive
charge. Carbon atoms are also positively charged. Dipole moment of pyridoxine
molecule value is high 2,2 Debye unit,
it explains good pyridoxine solubility in water and other polar solvents. HOMO
and LUMO energy equals -9,16 and -0,06 eV respectively. Pyridoxine molecule
has LUMO with low negative energy value so it belongs to electrophiles. The
main reactive molecule centers are oxygen and nitrogen atoms.
The
similar calculations were performed for riboflavin molecule. The most electric
density is localized in oxygen atoms. Nitrogen atoms are positively charged (+0,18; +0,11; +0,274; +0,394). The most
deficiency of electric density is localized near oxygen atoms. It evidences that oxygen is a centre of
protonization in riboflavin and hydrogen bonds can be formed between bioligands
(proteins, lipids, amino acids) and oxygen atoms.
Literature
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Ekins S., Erickson J.A., Testa B. ||Br. J.Pharmacol. – 2007-Vol. 152, ¹1,
p. 9-37
2.
Luis G., Valerio J. || Toxicol. Appl. Pharmacol. – 2009- Vol. 241, ¹3, p. 353-370
3.
Drapak V., Zymenkovskyi B. || Journal of
organic and pharmacological chemistry. — 2006. — V. 4, ed. 3(15). — P.
69-72