Polymers for Advanced Technologies Volume 7, pp. 723-725

Stacking between Pyrido(3,2-f) (l,’/)phenanthroline and Nucleic Bases Lei Wang, Xue Yi Le and Liang Nian Ji* Department of Chemistry, Zhongshan University, Guangzkou 51 0275, China

ABSTRACT

The stability constants of the terna y mixed ligand complex Mpdphen) (ATP)’-, where pdphen is the planar ligand pyrido(3,2-f) (1,7)phenanthroline, were determined by potentiometric pH titration in water, and in 30 and 50% (vlv) aqueous dioxane solutions. It has been observed from this information that a stronger stacking interaction between pdpken and the base of ATP exists and decreases with decreasing solvent polarity, i.e. increasing amounts of dioxane in the solvent mixture.

KEYWORDS: stacking; pyrido(3,2-f) (1 J)phenanthroline; phenanthroline; ATP

INTRODUCTION The interaction between mixed ligand complexes of ruthenium(I1) with polypyridyl and DNA has aroused much attention [ l l because the complexes may act as DNA secondary structure probes and, antitumor drugs. On the other hand, in our previous work [2], the interaction between a series of Ru(I1) complexes containing the ligand pyrido(3,2-f) (1,7)phenanthroline (pdphen) (Fig. 1) and DNA was studied using absorption, fluorescence and circular dichroism (CD) spectroscopies. The results showed

FIGURE 1. Pyrido(3,Zf) (1,7)phenanthroline.

* To whom correspondence should be addressed.

that the interaction between the polypyridyl com- plexes and DNA is mainly related to the stacking interaction between the polypyridyl complexes and DNA is mainly related to the stacking interaction between the intercalated polypyridyl and base pairs of DNA. However, this is only qualitative estimation. Therefore, we felt it desirable to extend our work to a more quantitative evaluation of the stacking interaction between polypyridyl and bases of DNA to explore various factors influencing the stacking interaction. It will be helpful to our understanding of the mechanism of interaction between intercalated ligand and base pairs of DNA.

EXPERIMENTAL In this work, the stability constants of the ternary complex formed by pdphen, ATP with a nucleic base and Cu2+ were measured by potentiometric pH titration in water, and in 30 and 50% (v/v) aqueous dioxane solutions. A comparison of the results with those of phen shows that a stronger stacking inter- action between pdphen and the nucleic base of ATP in the ternary complex is present and decreases with decreasing solvent polarity.

The acidity constants K&Am and KzATp of H,(ATP)’- were measured by titrating 50ml of aqueous 0.00094 mol/l HC10, and NaClO, (I=O.l mo1/1.25”C) in the presence and absence of 0.0005 mol/l ATP4- under N, with 0.1 mol/l NaOH. The pH of the solutions was measured with an Orion SA-720 pH meter using a Russel combination elec- trode. The conditions for the determination of the stability constants G:(ATp) and I@$pLE:;(ATp) of the binary Cu(ATP)’- and ternary Cu(pJphen)(ATP)’- complexes were the same as for the acidity constants, but NaClO, was fully or partly replaced by Cu(ClO,),. All these calculations were made on an IBM 80286 Computer.

Reaction solutions containing metal ions were immediately titrated after mixing to prevent dephos-

CCC 1042-71 47/96 / 07072M3 0 1996 by John Wiley & Sons, Ltd.

Received 2 November 2 995 Accepted 30 l a m a y 1996

724 / Wang eta1

TABLE 1. Negative Logarithms of the Acidity Constants of H2(ATP)'- and the Average of the Logarithms of the Stabiliy Constants of Binary and Ternary Complexes (0.1 mol/l NaClO,, 25°C)"

Water 4.02k0.02 6.48k0.03 6.42k0.07 6.92k0.04 6.97k0.03 (4.01 tO.O1)b (6.49k0.01) (6.32k0.04) (6.88k0.07)

30% dioxane 3.79k0.03 6.85k0.01 6.44k0.02 6.48t0.03 6.43t0.04 (3.68k0.02) (6.82k0.01) (6.40k0.05) (6.37k0.02)

50% dioxane 3.65k0.05 6.95k0.07 6.51 k0.03 6.1 8k0.03 6.06t0.03 (3.59k0.02) (6.90k0.02) (6.3420.05) (5.93 k0.07)

a The errors given are three times the standard errors ( 3 ~ ) . The data in brackets are from the literature [4].

phorylation [31. The acidity constants KE2ATp and KzATp of

H,(ATP)2- were calculated using eqs (1) and (2) respectively from the experimental data obtained by potentiometric pH titrations:

H2(ATP)2-= H(ATP)3- + H+ (1)

H(ATP)~- = ATP- + H+ (2)

RESULTS The results are listed in Table 1 and are in fair agreement with the corresponding values in the literature 141.

The stability constants of the binary CU(ATP)~- and ternary Cu(pdphen)(ATP)2- complexes are defined by eqs (3) and (4) respectively:

Cu2++ATP- =CU(ATP)~- (3)

Cu(pdphen)2+ + ATP4- = Cu(pdphen)(ATP)'- (4)

p ( p d p h e n ) [Cu(pdphen)(ATP)2- I [C~(pdphen)~+][(ATP)~- I Cu(pdphen)(ATP) =

The results are also summarized in Table 1 together with the corresponding data of phen. To our knowledge, the stability constants of the ternary complex in all three solvents are determined for the first time.

Equation (5) represents a common way to charac- terize the stability of the ternary complex:

1 O A WL = [Cu(pdphen)(ATP)2- J[Cu'+I [Cu(ATPI2- I[Cu(pdphen)'+ 1

The corresponding equilibrium constant may be

calculated by the following equation:

the obtained A IogK,, values are assembled in Table 2, together with the related data of phen.

DISCUSSION It is evident from Table 2 that A log&, values for pdphen are larger in all three solvents than the expected values ( ~ 0 . 9 ) on a statistical basis [4]. This increased stability depends clearly on the stacking between the aromatic ring of pdphen and the base of ATP in the ternary complex as described for A IogK,, values of phen in the literature [41. With the method described in the literature [4] the percentages of the isomer with the stacking interaction (C1%) for the ternary Cu(pdphen) (ATP)'- complex can be esti- mated by comparing A IogK,, values of phphen with the corresponding data of phen. The resuts are listed in Table 2. From Table 2, it is interesting to see that the degree of formation of intramolecular stacks in Cu(phen)(ATP)2- and Cu(pdphen)(ATP)2- are sim- ilar in water, but in aqueous dioxane solutions, the stacking of pdphen is larger than that of phen. The reason for this observation may be that, in a dioxane- water medium, an intramolecular stacking interaction primarily depends on the ring size of polypyridyl ligands, but in a water medium the hydrogen bonding between a water molecule and the uncoordinated N atom in pdphen may inhibit the stacking interaction between pdphen and the base

TABLE 2. The Alo kU Values and Percentages of the

Three Different Solvents (25"C, 0.1 mol/l NaClO,)

~(pdphen) A log&, =lo&u(pdphen)(ATP) - l0gG:(ATP) (6)

Closed Isomer for Cu(p lY phen) (ATP)'- and Cu(phen) (ATP)'- in

ligand Solvent A l 0 g K C " CI (%)

pdphen Water 0.50 30% Dioxane 0.04

phen Water 0.55

30% Dioxane -0.01

50% Dioxane -0.45

50% Dioxane -0.33

(0.56)"

(-0.03)

(-0.41)

a The data in brackets are from the literature 141.

91 67 57 92

(92) 62 (62) 46 (49)

Stacking between pdphen and Nucleic Bases / 725

part of ATP, making the stack of pdphen similar to that of phen.

Another interesting result that may be seen from Table 2 is that the degree of formation of the closed isomer in both complexes decreases somewhat by going from water to 50% (v/v) dioxane-water. The fact that the intramolecular stacking interaction between the aromatic ring of phen or pdphen and the adenine moiety of ATP can be inhibited by dioxane added to an aqueous solution may be attributed to an increasing hydrophobic solvation of the adenine moiety by the ethylene groups of the organic solvent, rendering the stack between aromatic rings more difficult [41.

To conclude, pdphen can undergo a stronger stacking interaction with the base of ATP and this interaction decreases with decreasing solvent polar- ity. These results can help us to understand the

nature of the interaction of ruthenium(I1) poly- pyridyl complexes with DNA.

ACKNOWLEDGMENT This work was supported by the National Natural Science Foundation of China and the Royal Society of Chemistry Research Fund 1995.

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