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RNA crystal structures have provided a wealth of information on localized metal ions that are bound to specific sites, such as the RNA deep groove, the Hoogsteen face of guanine nucleotides and anionic phosphate oxygens. With a number of crystal structures being solved with heavy metal derivatives and other “reporter” ions, sufficient information is available to estimate global similarities and differences in ion binding properties and to begin determining the influence of RNA and ions on each other. Here we will discuss the ions that are observed bound to RNA, their coordination properties, and the roles they play in RNA structural studies. Analysis of the crystallographic data reinforces the fact that ion interactions with nucleic acids are not easily interchanged between similarly charged ions. The physiological relevance of RNA-ion interactions, mainly involving K+ and Mg2+ cations, needs to be analyzed with care as different structures are solved under very diverse ionic conditions. The analysis is complicated by the fact that the assignment is not always accurate, often done under sub-optimal conditions, which further limits the generalization about the types of interactions these ions can establish.

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The interactions of Run(tpy)(bpy)OH22+ (I), RuII(tpy)(phen)OH22+ (2), and Ruu(tpy)(tmen)OH22+ (3) (tpy = 2,2',2"-terpyridine, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, tmen = A',A',Ar',N'-tetramethylethylenediamine) with DNA have been investigated by cyclic voltammetry. The addition of DNA to solutions of these complexes causes a dramatic decrease in current for the Ru(IV/III) and Ru(III/II) couples indicative of binding of the complexes to DNA. From the decrease in current, binding constants 15 x 101 23 M'1, 78 X 103 M'1, and 5.3 X 103 M"1 can be estimated for 1-3, respectively. Thus, the binding affinity appears to be partly a function of the extended planarity and aromaticity of the bidentate ligands. The previously reported activity of the Ru(IV) state toward DNA cleavage is apparent as a current enhancement in the Ru(IV/III) oxidation wave. As a result

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A group of seven mono-and diaquapolypyridyl complexes of Ru(II) have been shown to bind covalently to DNA by ultrafiltration, extensive dialysis, and ethanol precipitation. Incubation of the metal complex with calf thymus DNA in 50 mM phosphate buffer produces solutions of DNA exhibiting visible absorptions clearly due to the metal complex. These absorptions remain unchanged upon prolonged ultrafiltration or dialysis, demonstrating covalent binding of the metal complex to the DNA. Determination of the amount of bound metal complex either from the spectrum of the labeled DNA or from quantitation of the free metal complex in the filtrate obtained following ultrafiltration gives rb = [Ru]b/[DNA-nucleotide phosphate] = 0.01-0.02 for all of the complexes. Circular dichroism (CD) spectroscopy of the filtrate obtained following the reaction of DNA with racemic Ru(phen)2(py)OH22+ shows an enrichment of the solution in the A isomer by comparison with the known CD spectrum of the complex. Careful quantitation of the degree of enrichment in the filtrate shows that 90 ± 2% of the complexes bound to DNA are the A isomer, giving an enantiomeric excess for binding of the A isomer of 80 ± 4%. Other chiral complexes give lower selectivities, although the A isomer is preferred in all of the tested cases.Registry No. Ru(tpy)(bpy)OH22+, 20154-63-6; Ru(tpy)(phen)OH22+, 101241-02-5; Ru(tpy)(tmen)OH22+, 127714-17-4; Ru(bpy)2(OH2)22+, 72174-09-5; Ru(bpy)2(py)OH22+, 67202-42-0; Ru(phen)2(OH2)22+, Ru(phen)2(py)OH22+, 47768-50-3. Formation and Reactions of Monoand Bis(peralkylcyclopentadienyl) Complexes of Calcium and Barium. The X-ray Crystal Structure of [ (Me4EtC5)Ca()U-ttSiMe2CH2CH2&iMe2) ]2

The development of new DNA cleavage agents is of interest for the designing of synthetic restriction enzymes,"] for an understanding of the structure of DNA, ['] and for pharmaceutical application^.^^] We have recently directed our ef-forts at investigating functional metal complexes that initiate DNA cleavage by unusual mechanisms,141 and have reported efficient cleavage of DNA by the dicationic complex lL5I (bpy = 2,2'-bipyridine, tpy = terpyridine). 1 was generated via oxidation of 2 [Eqs. (a) and (b)J.["J [Ru"OHz(bpy)(tpy)12+ [Ru"'OH(bpy)(tpy)12+ + e-+ H + (a) 2 [Ru"'OH(bpy)(tpy)12+ [ R~'~O ( b p y ) ( t p y ) ]~+ + e -+ H + (b) 1The DNA cleavage with 1 can be effected either stoichiometrically by addition of 1 to the DNA or electrocatalytically by application of a potential of 0.8 V to a solution of DNA and 2.['I In attempts to increase the binding affinity of these agents, we have now prepared the dicationic complex 3 (dppz = dipyridophenazine, see Scheme 1).The planar dppz ligand imparts high DNA affinity to the complex 4."] Studies with topoisomerase showed that 4 unwinds DNA by 30°, strongly implicating an intercalative binding mode. Complex 4 has very attractive photophysical properties, but does not exhibit DNA cleavage reactivity. Complex 3 also exhibits a high DNA affinity while retaining the DNA cleavage reactivity of the Ru"OH,/RU'"O functionality. Furthermore, the X-ray crystal structure of this complex shows extensive x-stacking of the planar dppz ligand (see Fig. 3), which may provide insight into the high DNA affinity of dppz complexes.Reaction of Ru (tpy)Cl, with dppz in the presence of triethylamine affords the complex [RuCl(dppz)(tpy)]CI. Treatment of an aqueous solution of this complex with AgCIO, leads to the precipitation of 3-(C104), . H,O, in the form of black crystals suitable for X-ray structure analysis. The complex exhibits a typical Ru" --t py(x*) metal-ligand charge transfer (MLCT) absorption band with A,,,,, = 482 nm (E = 12000 M-lcm-'). In aqueous solution, the complex is oxidized sequentially to the dicationic Ru" complex [Eqs. (c) and (d)]. 3 [Ru'"OH(dppz)(tpy)]*+ + e -+ H' (C) [Ru"'(dppz)(tpy)12+ [ R~'~O ( d p p z ) ( t p y ) ]~+ + e -+ H + ( 4 5 At pH 7, E,,,(Ru~"/Ru") = 0.56 V and E,,,(Ru'"/Ru"') = 0.62 V (SCE), compared to 0.49 V and 0.62 V in the case of the complex 2.[61 The pK, value of the aqua ligand in 3 is 8.6 compared to a pK, of 9.7 in 2.16] The structure of 3 is shown in Figure 1 .[81 The coordination about the Ru center is very similar to that in both [R~"OH,(tmen)(tpy)]~+ (tmen = N,N,N',N',-tetramethylethylenediamine)lgl and 2." Thus, incorporation of the strongly intercalating dppz ligand has not altered the electronic properties of the Rul'OH, functionality that are vital to the DNA cleavage reactivity.Complex 3 binds very strongly to DNA. We have determined the binding constants for a series of complexes related to 2 using an electrochemical method based on the cyclic voltammetric currents for the Ru"'/Ru" redox pairs of the complexes with and without DNA.1...

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