Donor / Acceptor Properties of Purine and Р yrimidine Bases

We have studied the relative positions of the frontier levels determine the main electronic properties and reaction ability, there is important necessity to compare the MO of the purine and рyrimidine bases: adenine (A), guanine (G), cytosine (C), thymine (T) and uracil (U). The donor and acceptor properties are the fundamental characteristic of the conjugated molecules and can be quantitatively estimated by relative positions of the frontier molecular orbitals. The MO’s energies can be estimated experimentally or quantum-chemically. Analysis of the relative position of the frontier levels (calibrated by the energy gap) enables the investigation of the donor/acceptor properties of the RNA/DNA bases more detailed. The index φ0 is proposed for the quantitative quantum-chemical estimation of the donor ability of the conjugated molecules: it points on the shifting of the energy gap relative to the reference electron balanced system. The RNA/DNA bases divided strictly by two groups: predominantly donors (φ0 > 0.5) and predominantly acceptors (φ0 > 0.5). Each representative base of the first group forms the stable base pair the representative base of the second group the difference of indices Δφ0 should be optimal to enables the DNA replication.


Introduction
The nucleic bases -adenine, thymine, guanine, cytosine and uracil are wide known building blocks of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).A determination of their electronic structure is a great interest so as the NA bases are exceptional stable complex molecular assembly with respect to exposure of various environmental factors (Zinger, 1984).It is well known that NA basеs can generate the long chain owing to formation of the hydrogen bonding between pair of NA bases; such H-bonding is established to be main type of the intermolecular and intramolecular interactions which are responsible to biological process' (G.R. Desiraju, T.Stainer, 1999;Grabowski S.J., 2001).Similar non-covalent interactions specify the spatial constitution of the RNA/DNA chains and their physical and chemical properties in the ground and excited states.Besides the experimental study, the NA bases are favorite objects for investigation of electron structure of the individual base molecules as well as their interaсtions between them (M.Preuss, et al., 2004;S. S. Wesolowski et al., 2001;Daniele Varsano et al., 2006).Aromatic π-π stacking interactions are generally defined as the attractive interactions that occur between the π-clouds of aromatic systems in a parallel, face-to-face orientation.They play a fundamental role in many aspects of chemistry and biochemistry (C. A. Hunter, J. K. M. Sanders, 1991; S. K. Burley, G. A. Petsko, 1985), for example in the fields molecular recognition (E. A. Meyer et all, 2003) self-assembly (C.G. Claessens, J. F. Stoddart, 1997) supramolecular chemistry, and general host-guest interactions (B.Askew et al., 1989;D. B. Smithrud, F. Diederich, 1990;C. A. Hunter, 1994;J. Rebek, 1996).π-π -stacking in biology is often integral to the structure and function of proteins, cofactors and substrates (G.B.McGaughey et al.,1998).
While individually weak, the additive power of these interactions leads to large effects, DNA structure being the quintessential example (J.D. Watson, H. C. D. Crick, 1953).In such intricate scenarios, very often the π-π interaction is considered as some sort of "deus ex machine", intervening in reactions, stabilizing complexes, and influencing structure.Therefore, being able to estimate the energetic and structural features of these interactions would be extremely useful in modeling and understanding many important phenomena (Mark P Waller et al., 2006).The results of numerous studies show that many properties of NA bases, in particular, their affinity to other biomolecules depend on relative positions of their molecular levels, firstly, the frontier levels and levels of lone electron pairs of the two-coordinated nitrogen atoms capable to generate the hydrogen bonds.The MO energies can be estimated experimentally, for example, by photoelectron spectra (Timo Fleig, Stefan Knecht, 2007) or by quantum-chemical calculations (Vasily A. Ovchinnikov, Dage Sundholm, 2014;O.O. Brovarets' et al., 2014;Daniel Svozil et al., 2004).In addition, to obtain reasonable accuracy for small electron affinities, electronic energies have to be calculated with as high precision as possible.This criterion includes sustaining the accuracy in calculating the atomic integrals, tightening the convergence criteria in the SCF and post-SCF calculations, etc. Obviously, the challenge of evaluating accurate electron affinities becomes more and more difficult as the size of the molecule or complex grows (Anil Kumar et al., 2004).
Using reversible reduction potentials, Wiley (J.R. Wiley et al., 1991) obtained electron affinities of the purine and pyrimidine bases of nucleic acids experimentally.Chen (E. C. M. Chen, E. S. D.Chen, N. Sane, 1998) calculated the EAs of A, G, C, T, and Uracil (U) using semiempirical AM1-MCCI (multiconfigurational configuration interaction).Their AM1-MCCI values were found to be in good agreement with the experimental values for all the bases (E.C. M.Chen, E. S. D. Chen, 2000).Scheidt (J.Schiedt, R. Weinkauf, D. M. Neumark, E. W. Schlag, 1998) investigated the electron binding to DNA bases U, T, and C in the presence of water clusters using photodetachment-photoelectron spectroscopy (PD-PES).They found positive electron affinities (EA) in the 62-86 ±8 meV range for dipole-bound states of the bases.For U and T, they detected one dipole-bound state, while for cytosine, they found two dipole-bound states (85 ± 8 and 230 ± 8 meV).
So, as the relative positions of the frontier levels determine the main electronic properties and reaction ability, there is important necessity to compare the MO energies with energies of the other conjugated molecules.It was earlier proposed to characterize the donor properties of the linear conjugated molecules (α,ω-disubstitutedpolyenes and polemethines) by the shifting of the frontier levels caused by introducing of terminal substituents (Kachkovskiy A.D., 1997).
Similar approach likely can be used to theoretical estimation of the donor/acceptor properties of NA bases and their analogues.

Electron donor ability of π-electron molecules
Earlier it was proposed (Kachkovskiy A.D., 1997) to estimate quantitative donor/acceptor properties of conjugated molecules by the relative positions of their frontier molecular levels using the following formulas: Where εLUMO is an energy of the lowest molecular orbital; εHOMO is an energy of the highest occupied MO, while α is so-called Coloumb integral (in framework of Hükel approximation), which corresponds to an energy of 2pz electron of the carbon atom in sp 2 -hybridyzation.In the neutral linear conjugated systems, polyenes1, polymethine radicals 2 or polyacenes 3, as shown earlier (Pilipchuk N.V., Kachkovski O.D. et al., 2005) parameter α is equal the energy gap middle.
Indeed, the calculations show that the frontier electron levels in chain of the unsubstitued polyenes1 approach to each other regularly upon lengthening of the conjugated chain, so that distance between them decreases, as one can see 3 demonstrably for the levels of polyenes1obtained by three various methods (M.J. Frisch, G. W. Trucks et al., 2003) in Table 1(a-c).

Table 1b
Unsubstituted polyenes 1. Frontier Level Energies ((εi,a.u.)It is clear seen that the levels for electron with the opposite spins approach regularly; the gap middles approach also, so that the value δ/2 tends to the magnitude-0.095a.u., found for the polyenes 1.
The practically the same value δ/2 is obtained for the third type of neutral linear In the study of the polymethine dyes and α,ω-disubstitued polyenes, the parameter ϕ0 point on the shifting the energy gap upon introducing of the donor/acceptor terminal residues.
The analogical approach could be used for estimation the donor/acceptor conjugated molecules, particularly, various heterocycles, including the DNA bases.

Donor abilities of heterocycles
For sake an illustration, let us present the simplest heterocycles containing the nitrogen atom and/or other heteroatoms.In Table 2, the frontier level energies as well as the parameter ϕ0for the 6-membered nitrogen-containing heterocycles 4-6 and 5-membered heterocycle 7-8 are collected.In a contrast, the 5-membered cycles 7 should be considered as electron-sufficient conjugated molecules: a number of π-electrons exceed a number of π-centers.Then both frontier levels shift thereafter up so that the gap middle is found closer to the highest occupied level; in accordance with this, the parameter ϕ0 increasesalsowhat point in increasing of the donor ability.
The variation of the heteroatom X cause change of the donor/acceptor properties upon going from furan (X = O) to azole (X = NCH3) or thiophene (X = S): ϕ0 = 0.604; 0.551; 0.499, i.e. the decreasing of the heteroatom X electrononegativity is accompanied by regular decreasing of the acceptor ability.
Introducing additionally of the nitrogen atom in the 5-membered heterocycle 8 causes the shifting of energy gap down, and hence such chemical change increases acceptor ability, so that δϕ0≈0.6 upon going from 8, X = NH to 8, X = O and δϕ0≈0.4upon going from 8, X = O to 8, X = S.
It is to be also noted that the HOMO and the LUMO demonstrate the different sensitivities to the changes of the chemical constitution and hence the change of the energy gap Δ does not correlate with the donor/acceptor parameter ϕ0.

Estimation of donor/acceptor ability of NA bases
Generally, the bases in the DNA subunits are connected sequentially with ribose, deoxyribose and phosphorus residues.However here we will study the model heterocylic bases 9-13, when the base tails are modeled by the saturated methyl (-CH3) group (Figure 4).The calculated frontier level energies and other characteristics of the studied purine and рyrimidine bases 9-13 are collected in Table 3.At first, all three used methods give the comparatively close values for the proposed donor/acceptor parameter ϕo, in spite of the more essential differences in MO energies.The both DFT-method staking into consideration the electron correlation give somewhat higher values than simple HF approximation with the bases set.However, all three methods show the same So, three bases, U, C, T, are composed of 6-memvered cycle with the exocyclic onecoordinated oxygen atom giving one 2pz electron in total conjugated system; also, cyctosine and thymine have the exocyclic amino group with two electrons included in the π-system, so that each molecule has its stable electron shell.Because of the heavy atoms, the heterocyclic bases C and T should demonstrate the principally acceptor properties.As regards to U, it contains two t one-coordinated oxygen atoms (giving two electrons in the total π-system); two tri-coordinated nitrogen atoms give four electrons (at the expense of their LEPs).But, though bases U, C, T are electron-sufficient systems, so they are acceptors because of the heavy nitrogen atoms existence in their structure.
In contrast, the heterocyclic bases A and G contains 5-membered cycle with the tricoordinated nitrogen atom with its LEP with makes these molecules as high donor π-system; thus, their parameters are higher the middle value: ϕo > 0.5, i.e. they should give evidence of their donor properties.The tendency predicted all used methods is seen from presented data in Table 3 to be the same.
In simple approaches of molecular orbital theory, the HOMO energy (εHOMO) is related to the ionization potential (IP) by Koopmanns' theorem and the LUMO energy (εLUMO) has been used to estimate the electronaffinity (EA).As it seen from the Table 4, parameter φ сhanging in the same direction as measured practically ionization potential (Orlov V. M., Smirnov A. N., Varshavsky Ya. M., 1976) and electronaffinity (J.R. Wiley, J. M. Robinson et al., 1991).Nevertheless our experimental data confirm the general conclusion made of these publications, that the purine bases are better electron donors than the pyrimidines.

Comparison of donor/acceptor abilities of the heterocyclic bases of NA
It is known that the RNA/DNA bases make up the bases pair in DNA chain molecules, so that thestable A-T and G-C pairs are formed, they are connecting by two/three bonding bonds (Zinger, 1984).Besides, the pyrimidines are bonded with the purines; other possible pairs turn out to be unstable.Then, let us compare the indicesof the pyrimidine bases with the reference long polyene molecule 1 and the pyrimidine 5.The Figure 5 shows distinctly that the U (uracil) and C (cytosine) should predominately treat as acceptors, similarly to the pyrimidine heterocycle 5, as far as their ϕo < 0.5.Introducing of the donor methyl (-CH3) substituent in the uracil and hence going to thymin (T) leads to shifting of the frontier levels up and to decreasing of the acceptor property (see increasing of the index ϕo in Table 3).likely not stable.Evidently, there is certain optimal difference Δφ 0 in order to the base pair should be stable and also enables the DNA replication.The existence of the optimal difference in donor/acceptor properties seemly explains the well-known complementarity rule of nucleobases (Zinger, 1984).

Conclusion
Thus, an analysis of the relative position of the frontier levels (calibrated by the energy electron correlation give the regular somewhat increasing of MO energies because of the considerable polarization of the C−H bonds.In the Huekel method, the energy gap in the unsubstituted polyenes 1 correspond to Coulomb integral α by the definition, as can be seen from Figure 1.

Figure 4 .
Figure 4. General structure of studied purine and рyrimidine bases.
/acceptor parameter on the chemical constitution of the DNA/RNA heterocyclic bases.

Figure 7 .E
Figure 7. Indices φ 0 for RNA/DNA bases gap) enables the investigation of the donor/acceptor properties of the RNA/DNA bases more detailed.The index φ 0 is proposed for the quantitative quantum-chemical estimation of the donor ability of the conjugated molecules: it points on the shifting of the energy gap relative to the reference electron balanced system.The RNA/DNA bases divided strictly by two groups: a) predominantly donors (φ 0 >0.5); b) predominantly acceptors (φ 0 >0.5).Each representative base of the first group forms the stable base pair the representative base of the second group (complementarity rule) the difference of indices Δφ 0 should be optimal to enables the DNA replication.

Table 4
Correlation of the calculated parameter φ with practically measured EA and IP.