1. Introduction

The specific interactions between the purine and pyrimidine bases are one of the corner stones of the molecular biology[1-4]. It is well known[5] that hemoglobin provides an excellent illustration of quaternary structure. Each unit of hemoglobin is composed of α 2 and β2 chains. Hemoglobin is normally formed in the body. If any malfunctioning occurs in its formation[6] due to genetic or any other causes, several diseases like thalasemia, sickle cell anemia, excess Fe⁺² accumulations etc. appear in the body. If this excess Fe⁺² be removed by complexation with either of the purine or pyrimidine bases then there may be some possibilities of curing the above diseases. Previously chelate therapy was used to treat excessive quantities of copper in the body[6]. Keeping this view in mind the present work has been undertaken to examine theoretically the reaction between Fe⁺² and adenine as the second case study because the complex with thymine has already been published[7].

2. Computational Details

Complete geometry optimizations for Fe⁺² (Adenine)₂ (H₂O)₂ complex were done in the gas phase by Hartree-Fock method with 6-31G(d) basis set using Gaussian 03W program[8]. Actually this optimization gives the most stable conformation of the system studied. Moreover for first hand information Hartree-Fock method with 6-31G(d) basis set is sufficient in comparison to more popular DFT method which requires much more computation time. Single point water phase calculations at the gas phase equilibrium geometry were also done using the same basis set by polarisable continuum model (PCM) approach at HF level. Here also optimization in water phase calculation is not done because of computation time problem.

3. Results and Discussion

Equilibrium geometry of the studied complex with the numbering scheme of the atoms is shown in figure-1 (a).The single point water phase calculations using the gas phase equilibrium geometry is shown in figure-1(b). The significant variations in these figures are indicated by some selective geometrical parameters given in Table-3. Table 1 reports in the gas phase the computed total energy (hartree), dipole moment (debye) and ΔE (HOMO-LUMO gap) (hartree), at the equilibrium geometry of the complex along with single point water phase data. Table-2 summarizes the computed net Mulliken charge on the selected hetero atoms of the complex at the equilibrium geometry of the complex in the gas phase including the single point water phase calculations. The hetero atoms are assumed to play the key role for the physiological drug action because these are the most negative centres of the complex. The drug action is assumed to take place through chemical attack.

From the Table 1, it is seen that the complex is highly stable in the gas phase at the equilibrium geometry. The stability is increased in the water phase because the total energy of the system in this phase is more negative than in gas phase. Mulliken population analysis is not unique; still it is very important to provide an idea of electron density distribution in a molecular system. The calculated dipole moment reflects an overall charge/electron density distribution in a molecular system. From Table -1 it is seen that the dipole moment of the complex in water phase is 1.5 times greater than that in gas phase as it is expected [polar complex in polar solvent]. The HOMO and LUMO both are little bit destabilized in water phase than the gas phase because the complex contains ten N-atoms.

From Table 2 it is seen that the Fe⁺² (in its closed shell configuration) ion receives 0.5072e and 0.4493e amount of charge respectively in gas phase and water phase from two adenine ligands and two water ligands. In almost all the hetero atoms the charge densities in gas phase is little less than that in the water phase implying that in water phase the negative centers become more effective for better physiological drug action.

HOMO and LUMO structures of the complex both in gas phase and single point water phase are shown in figure-( 2a, 2b )and figure- (3a, 3b) respectively. The significance of the figures is that complete geometry of the complex is seen which is not reflected from the selected geometrical parameters shown in Table-3. The LUMO structure shows that Fe⁺² ion plays the key role of the complex both in gas phase and water phase which is also supported from figures. Table-3 shows some selected geometrical parameters of the complex in the gas phase particularly the metal containing zone and other heteroatom containing zone. From table-3 it is seen that Fe⁺² containing zones are non planar and this part of the complex is out of plane from both the adenine ligands and two H₂O ligands also. Fe31 –N25 and Fe31-N11 distances are 3.6100 A° and 3.2200A° respectively. Fe31-N18 and Fe31-N12 distances are 2.0662 A° and 2.0610A° respectively. Fe31-O36 and Fe31-O33 distances are 2.0185A° and 2.0089A° respectively. The most stable conformation of the system favors such geometrical parameters.

Figure 1. (a) Optimized structure of Fe+2 (Adenine)2 (H2O)2 complex in gas phase. (b)Single point structure of Fe+2 (Adenine)2 (H2O)2 complex in water phase

Table 1. Computed total energies (hartree) dipole moments (debye), HOMO, LUMO energies (hartree) and ΔE( HOMO-LUMO gap)(hartree) at the equilibrium geometry of the ground state of Fe+2 (Adenine)2 (H2O)2 complex

Table 2. Computed net Mullikan Charge/electron density on the selected atoms of Fe+2 (Adenine)2 (H2O)2 complex at the equilibrium ground state and single point data in water phase Atoms Complex in Gas Phase Complex in Water Phase Atoms Complex in Gas Phase Complex in Water Phase H5 0.2223 0.2769 N19 -0.7887 -0.7995 H7 0.4546 0.4847 N24 -0.5558 -0.6336 N9 -0.5519 -0.6120 N25 -0.9845 -0.9853 N10 -0.8169 -0.8247 N26 -0.5754 -0.6506 N11 -0.9758 -0.9751 Fe31 1.4928 1.5507 N12 -0.9456 -0.9244 O33 -1.0180 -1.0302 N13 -0.5562 -0.6399 O36 -0.9883 -1.0040 N18 -0.9069 -0.8820 H34 0.5242 0.5494

Table 3. Computed values of some selected geometrical parameters (length in A0) at the equilibrium ground state of Fe+2 (Adenine)2 (H2O)2 complex. Atoms length Atoms length Atoms length C1-N12 1.3555 Fe31-O36 2.0185 N19-C21 1.3721 C1-N13 1.2911 Fe31-O33 2.0089 N19-H22 1.0005 C1-H5 1.0771 Fe31-N12 2.0610 C20-C21 1.3806 C2-N13 1.3301 Fe31-N18 2.0662 C23-N25 1.4021 C2-C3 1.3893 Fe31-N11 3.2200 C23-N26 1.3052 C4-N12 1.3479 Fe31-N25 3.6100 N24-C27 1.3118 C6-H8 1.0706 O36-H37 0.9619 N25-H28 1.0048 C6-N9 1.2810 O36-H35 0.9530 N25-H29 1.0056 C6-N10 1.3779 O33-H32 0.9756 N26-C27 1.3343 H7-N10 0.9989 O33-H34 0.9531 C27-H30 1.0723

Table 3. (continued) Computed values of some selected geometrical parameters (Angle in degree) at the equilibrium ground state of Fe+2 (Adenine)2 (H2O)2 complex. Atoms Angle in degree Atoms Angle in degree C20- N18- Fe31 131.07 Fe31-N18- O36-H35 -40.75 C1-N12-Fe31 116.75 Fe31-N18- O36-H37 172.16 C4- N12-Fe31 124.41 Fe31-O33- H34-N12 -58.37 C17-N18-Fe31 131.07 Fe31-N18-C20-N12 158.91 N12-Fe31-N18 160.57 Fe31-N11-C4-N12 10.08 N12- Fe 31-O33 96.10 Fe31-N12-C4-C3 -167.11 N12- Fe 31-O36 95.46 H5-C1-N13-C2 -179.88 N 18- Fe 31-O36 96.44 N12-C1-N13-C2 0.15 N 18- Fe 31-O33 97.51 N11-C4-N12-C1 179.63 O33-Fe31-O36 97.43 C4-N12-Fe31-O36 32.93 Fe31-O33-H34 126.69 C21-C20-C23-N26 3.11 Fe31-O36-H35 127.96 C21-C20-C23-N25 -178.93 H32-O33-H34 109.52 C17-N18-Fe31-O33 -142.66 Fe31-N18-C17-N12 -8.52 C23-N26-C27-H30 179.87 Fe31-N12-O33-H32 157.05 N9-C6-N10-H7 -179.16

Figure 2. (a) HOMO structure of Fe+2 (Adenine)2 (H2O)2 complex in gas Phase. (b) LUMO structure of Fe+2 (Adenine)2 (H2O)2 complex in gas Phase

Figure 3. (a) HOMO structure of Fe+2 (Adenine)2 (H2O)2 complex in water Phase. (b) LUMO structure of Fe+2 (Adenine)2 (H2O)2 complex in water Phase

4. Conclusions

From the present theoretical study it is found that the Fe⁺² (Adenine)₂ (H₂O)₂ Complex is a stable complex both in gas phase and in water phase (single point calculation by polarisable continuum model- PCM). This first hand information of the title complex signifies its physiological importance for the removal of excess Fe⁺² from the body. The LUMO structure shows that Fe⁺² ion plays the key role of the complex both in gas phase and water phase. The present study may help in the discovery of new drug.