مستخدم:Yazan.hawasheen/ملعب

Computational chemical studies of nitrogen base deamination:

Calculation theoretical studies for deamination reaction from nitrogen bases: in chemistry, deamination reaction includes removing amino group from organic

compound. This reaction has a vital importance through availability of bio-building blocks for life, also the importance in industrial level. Enzymes responsible for this reaction called deaminase enzymes, this interaction occurs in the human body mainly in the liver, and there are many calculated chemical studies which have been conducted on the mechanism of removing amino group from some nitrogen bases as the following:

1. Almatarneh et al. Study 2006 AD:

Theoretical calculation study using (MUN gauss) program for deamination reaction mechanism of Cytosine compound in the presence of water molecule (H2O) and Hydroxyl group (-OH) to produce Uracil compound.

Chemical calculations on Energy were conducted and structural formulas were coordinated for each reactant, transition states, intermediates, and products by using the following levels of theory: B3LYP/6-31G(d), MP2/6-31G(d), RHF/6-31G(d), and for negative ions using level of theory B3LYP/6-31+G(d). In addition, of determining single point by using levels of theory: MP2/GTMP2, G3MP2.

The study concluded that there are two tracks (A&B) for deamination reaction of Cytosine compound in the presence of water molecule, the first track represents reaction mechanism through five ways, these ways containing rate determining step by formation tetrahedral intermediate, second track contains reaction mechanism through two steps, one of them rate determining step by formation structural compound close to Uracil. Activation energies by using level of theory G3MP2 for rate determining steps were 221.3 kjol/mol and 260.3 kjol/mol for first track (A) and the second track (B) respectively, and this indicate the impossibility of occurring this reaction due to highly activation energy value. Also another two ways (C & D) for deamination reaction in the presence of hydroxyl group (-OH) through formation of tetrahedral intermediate after addition water molecule to dehydrogenated Cytosine compound, then it will be subjected to configurational changes end to dissociation of this intermediate to Uracil compound through proton transfer (proton shift, 3-1). The minimum activation energy that obtained was 148 kjol/mol by using G3MP2.

2. Zang et al. Study 2007 AD:

Theoritical calculations study using (Gaussian 98) program for deamination reaction mechanism of Adenine compound in the presence of water molecules (1 – 4 H2O molecules) producing Hypoxanthine compound.

Chemical calculations on Energy were conducted and structural formulas were coordinated for each reactant, transition states, intermediates, and products by using level of theory B3LYP/6-31G++.

The study concluded that the most acceptable track is by formation a tetrahedral compound with the aid of hydration followed by deamination by C-N bond breaking and C=O bond formation. This study show that it is impossible to make deamination for Adenine in open system (connected with DNA sequence) due to high activation energies value for rate determining steps and that was 59.1, 42.9, 42.4, and 42.9 Kcal/mol, according to water molecule sequence (1 – 4 H2O molecules). With the possibility of reaction in closed system (separated Adenine) only in the presence of 3 and 4 water molecules due to the activation energy for rate determining step was 8.7 and 2.4 kcal/mol respectively, so one molecule will inter in the reaction while the others works as intermediate.

3. Almatarneh et al. Study 2008 AD:

Theoretical calculations study using (Gaussian 03) program for deamination reaction mechanism of Cytosine compound in the presence of water molecule with hydroxyl group (H2O/ -OH), and in the presence of tow molecules of water with hydroxyl group (2H2O/ -OH) to produce Uracil compound.

Chemical calculations on Energy were conducted and structural formulas were coordinated for each reactant, transition states, intermediates, and products by using level of theory: B3LYP/6-31G(d), MP2/6-31G(d), and B3LYP/6-31+G(d). in addition to determine single point energy by using levels of theory: MP2/G3MP2L and G3MP2.

Study concluded that there are seven tracks for deamination of Cytosine compound whether in the presence of one or two water molecules, whereas all of these tracks are similar in formation of tetrahedral intermediate in rate determining step, then subjected to configurational changes in terms of geometrical arrangements for amine and hydroxyl groups that ending to dissociation this intermediate compound to Uracil through proton transfer (Proton shift, 3-1). The lowest activation energy value for rate determining step was through fourth track (D) with 115.3 kjol/mol, by using level of theory G3MP2 which was acceptable with experimental results equal to 117 kjol/mol.

4. Kabaer Aldeen, Almatarneh et al. study 2011 AD:

Theoretical calculations study using (Gaussian 09) program for deamination reaction mechanism of Guanine compound in the presence of water molecule or with hydroxyl group (-OH) or both (H2O/ -OH), and deamination reaction of Guanine-H+ with water molecule to produce Xanthene compound.

Structural formulas were coordinated for each reactant, transition states, intermediates, and products by using level of theory: MP2/6-31+G(d), RHF/6-31G(d), and B3LYP/6-31G(d), also energy chemical calculations were conducted at high levels of theory: G3MP2, G4MP2, G3MP2B3, CBS-QB3.

Study concluded that all reaction tracks started by formation of tetrahedral compound then changed to another intermediate which then will be dissociated to Xanthene through (proton shift, 3-1). Activation energy that calculated through level of theory G3MP2 to rate determining step in the presence of Hydroxyl group was 155 kjol/mol in comparison with 187 and 234 kjol/mol in case of reaction with water molecule for each Guanine and Guanine-H+ respectively, the lowest activation energy was calculated at level of theory G3MP2 for deamination reaction of Guanine compound with water molecule and hydroxyl group (H2O/ -OH), and due to the absence of a similar study, results had been compared with deamination of Cytosine compound.

5. Alrawashdeh and Almatarneh Study 2013 AD:

Theoretical calculations study using (Gaussian 09) program for deamination reaction mechanism of Adenine with three water molecules or with nH2O/-OH, where n=1-3 water molecules, to produce Hypoxanthine compound.

Structural formulas were coordinated for each reactant, transition states, intermediates, and products by using level of theory: MP2/6-31G(d), B3LYP/6-31G(d), HF/6-31G(d), and B3LYP/6-31+G(d), also energy chemical calculations were conducted at high levels of theory: G3MP2B3 and CBS-QB3.

Study concluded that five tracks (E-A) to deamination reaction of Adenine with three water molecules or with nH2O/OH. The first four tracks started by deprotonation of Amino group of Adenine compound by –OH, while track E started with Adenine compound formation, then all reaction tracks were similar in formation of tetrahedral intermediate compound which in turn dissociates to Hypoxanthine in rate determining step reaction. The highest activation energy calculated through level of theory G3MP2B3 in the presence of one Hydroxyl molecule –OH was 190 kjol/mol, with adding water molecule activation energy decreased to 68 kjol/mol, and it significantly decreased with adding water molecules. The most acceptable reaction mechanism is for track E in the presence of three water molecules with activation energy 139 kjol/mol without solvent and 137 kjol/mol in the presence of solvent as a catalyst, where activation energy decreased significantly from 2 to 6 kjol/mol in the presence of hydroxyl group (-OH) for each tow cases.

6. Almatarneh et al. Study 2006 AD:

Theoretical calculation study using (Gaussian 09) program for deamination reaction mechanism of Melamine with hydroxyl group (-OH), or with nH2O/-OH where n= 1 – 3 water molecules, also deamination study for Melamine-H+ with one water molecule.

Structural formulas were coordinated for each reactant, transition states, intermediates, and products by using levels of theory: B3LYP/6-31G(2df,p), B3LYP/6-31+G(d), B3LYP/6-31G(d), M06/6-31G(d) and B3LYP/6-31111G(3df,3pd), also energy chemical calculations were conducted at high levels of theory: M06/6-31+G(d) and ωB97XD/6-31+G(d).

All compounds modified their structural optimization in Aqueous medium (water as a solvent) by using level of theory B3LYP/6-311G(d,p) in polarized and non-polarized mode, and take into account electron density of the solvent. This complex way calculated by using level of theory with high accuracy: G4MP2 and CBS-QB3.

Study concluded that there are fifteen tracks for deamination process to Melamine compound, most of these tracks started with tetrahedral compound formation which in turn will dissociates by 1,3- Proton shift. The lowest activation energy was calculated by level of theory G4MP2 111 kjol/mol in the precense of three water molecules with hydrxyl group (3H2O/-OH).