Adenine Radical Cation Formation by a Ligand-Centered Excited State of an Intercalated Chromium Polypyridyl Complex Leads to Enhanced DNA Photo-oxidation.

Assessment of the DNA photo-oxidation and synthetic photocatalytic activity of chromium polypyridyl complexes is dominated by consideration of their long-lived metal-centered excited states. Here we report the participation of the excited states of [Cr(TMP)2dppz]3+ (1) (TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline; dppz = dipyrido[3,2-a:2',3'-c]phenazine) in DNA photoreactions. The interactions of enantiomers of 1 with natural DNA or with oligodeoxynucleotides with varying AT content (0-100%) have been studied by steady state UV/visible absorption and luminescence spectroscopic methods, and the emission of 1 is found to be quenched in all systems. The time-resolved infrared (TRIR) and visible absorption spectra (TA) of 1 following excitation in the region between 350 to 400 nm reveal the presence of relatively long-lived dppz-centered states which eventually yield the emissive metal-centered state. The dppz-localized states are fully quenched when bound by GC base pairs and partially so in the presence of an AT base-pair system to generate purine radical cations. The sensitized formation of the adenine radical cation species (A•+T) is identified by assigning the TRIR spectra with help of DFT calculations. In natural DNA and oligodeoxynucleotides containing a mixture of AT and GC of base pairs, the observed time-resolved spectra are consistent with eventual photo-oxidation occurring predominantly at guanine through hole migration between base pairs. The combined targeting of purines leads to enhanced photo-oxidation of guanine. These results show that DNA photo-oxidation by the intercalated 1, which locates the dppz in contact with the target purines, is dominated by the LC centered excited state. This work has implications for future phototherapeutics and photocatalysis.

Synthesis of cis-[Cr(diimine)2(1-methylimidazole)2](3+) Complexes and an Investigation of Their Interaction with Mononucleotides and Polynucleotides.

A protocol is presented for the synthesis of chromium(III) complexes of the type cis-[Cr(diimine)2(1-methylimidazole)2](3+). These compounds exhibit large excited-state oxidizing powers and strong luminescence in solution. Emission is quenched by added guanine, yielding rate constants that track the driving force for guanine oxidation. The cis-[Cr(TMP)(DPPZ)(1-MeImid)2](3+) species binds strongly to duplex DNA with a preference for AT base sites in the minor groove and may serve as a precursor for photoactivated DNA covalent adduct formation.

Study of picosecond processes of an intercalated dipyridophenazine Cr(III) complex bound to defined sequence DNAs using transient absorption and time-resolved infrared methods.

Picosecond transient absorption (TA) and time-resolved infrared (TRIR) measurements of rac-[Cr(phen)2(dppz)](3+) () intercalated into double-stranded guanine-containing DNA reveal that the excited state is very rapidly quenched. As no evidence was found for the transient electron transfer products, it is proposed that the back electron transfer reaction must be even faster (<3 ps).

Effect of ancillary ligands on the DNA interaction of [Cr(diimine)3]3+ complexes containing the intercalating dipyridophenazine ligand.

The synthesis of photoluminescent Cr(III) complexes of the type [Cr(diimine)(2)(DPPZ)](3+) are described, where DPPZ is the intercalating dipyridophenazine ligand, and diimine corresponds to the ancillary ligands bpy, phen, DMP, and TMP (where bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, DMP = 5,6-dimethyl-1,10-phenanthroline, and TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline). For TMP, DMP, and phen as ancillary ligands, the complexes have also been resolved into their Lambda and Delta optical isomers. A comparison of the photophysical and electrochemical properties reveal similar (2)E(g) --> (4)A(2g) (O(h)) emission wavelengths and lifetimes, and a variation of 110 mV in the (2)E(g) excited state oxidizing power. A detailed investigation has been undertaken of ancillary ligand effects on the DNA binding of these complexes with a range of polynucleotides. For all four complexes, emission is quenched by the addition of calf thymus B-DNA, with the emission lifetime data yielding bimolecular quenching rate constants close to the diffusion controlled limit. Equilibrium dialysis studies have established a general predilection for AT base binding sites, while companion experiments with added distamycin (a selective minor groove binder) provide evidence for a minor groove binding preference. For the case of [Cr(TMP)(2)(DPPZ)](3+), concomitant equilibrium dialysis and circular dichroism measurements have demonstrated very strong enantioselective binding by the Lambda optical isomer. The thermodynamics of DNA binding have also been explored via isothermal titration calorimetry (ITC). The ITC data establish that the primary binding mode for all four Cr(III) complexes is entropically driven, a result that is attributed to the highly favorable free energy contribution associated with the hydrophobic transfer of the Cr(III) complexes from solution into the DNA binding site.

Effects of steric constraint on Chromium(III) complexes of tetraazamacrocycles. 3. Insights into the temperature-dependent radiationless deactivation of the 2Eg (Oh) excited state of trans-[Cr(N4)(CN)2]+ complexes.

Macrocyclic complexes of the type trans-[Cr(N4)(CN)2]+, where N4 = cyclam, 1,11-C3-cyclam, and 1,4-C2-cyclam demonstrate significant variation in their room-temperature excited-state behavior; namely, the lifetimes of the 2Eg (Oh) excited states are 335, 23, and 0.24 micros, respectively. The lifetimes of these complexes have been measured in acidified H2O/dimethyl sulfoxide over the temperature range between -30 and +95 degrees C. Arrhenius activation parameters were calculated from these data. There was very little variation in the values of the Arrhenius preexponential factor between these three complexes, whereas the value of Ea is 40.6 kJ/mol for the cyclam complex, 35.5 kJ/mol for the 1,11-C3-cyclam complex, and 22.3 kJ/mol for the 1,4-C2-cyclam complex. Thus, differences in the room-temperature excited-state lifetimes can be rationalized based on the competition between thermally independent nonradiative relaxation and a thermally activated channel. To test whether a photodissociation mechanism involving Cr-macrocyclic N bond cleavage is a plausible explanation for the thermally activated relaxation pathway, samples of the cyclam complex were photolyzed in acidified D(2)O. A marked increase in the lifetime after photolysis demonstrated the occurrence of photodeuteration and thus a likely photodissociation of a macrocyclic N.

Capillary electrophoresis as a probe of enantiospecific interactions between photoactive transition metal complexes and DNA.

Recently, we have demonstrated the capacity to separate chiral transition metal (TM) complexes of the type [M(diimine)(3)](n+) using CE buffers containing chiral tartrate salts. In separate work, several chromium(III)-tris-diimine complexes in particular have been shown to bind enantioselectively with calf-thymus (CT) DNA, and a qualitative assessment of the relative strength and enantiospecificity of this interaction is of significant interest in the characterization of these complexes as potential DNA photocleavage agents. Here, we describe two convenient approaches to investigate such binding behavior using chiral CE. For complexes with lower DNA affinities exhibiting primarily surface binding, DNA itself is used as the chiral resolving agent in the electrophoretic buffer. In this approach, resolution of the TM complexes into their Lambda and Delta isomers is achieved with the isomer eluting later exhibiting superior binding affinity toward DNA. For more strongly bound TM complexes containing ligands known to intercalate with DNA, the [Cr(diimine)(3)](3+) complexes are preincubated with oligonucleotide and subsequently enantiomerically resolved in a dibenzoyl-L-tartrate buffer system that facilitates analysis of the unbound TM species only. Differences in isomer binding affinity are distinguished by the relative peak areas of the Lambda- and Delta-isomers, and relative binding strengths of different complexes can be inferred from comparison of the total amount of unbound complex at equivalent DNA/TM ratios.

Electronic energy self-exchange with macrocyclic chromium(III) complexes.

The luminescence lifetimes of N-deuterated Cr(III) complexes of macrocyclic tetraamine ligands, trans-CrN(4)X(2)(n)()(+), are substantially longer than those of their undeuterated counterparts in room temperature solution. Thus, excited-state emission quenching of the longer lived species by the shorter lived species may be studied by analyzing the decay profile following pulsed excitation. Flash photolysis experiments were carried out for three deuterated/undeuterated pairs of trans-CrN(4)X(2)(n)()(+) complexes (where X = CN-, NH(3), and F-). For the trans-Cr(cyclam)(CN)(2)(+) system in H(2)O, it was determined that energy transfer was occurring between the deuterated and undeuterated species. Although the rate constant of energy transfer was too fast to measure explicitly, it could be bracketed as k(et) >>7 x 10(6) M(-1) s(-1). For this reaction it was possible to measure an equilibrium constant which was very near 1.0. For trans-Cr(cyclam)(NH(3))(2)(3+) in DMSO, it was also established that energy transfer was occurring and rate constants of 2.4 x 10(6) M(-1) s(-1) (mu = 0.1) and 9.7 x 10(6) M(-1) s(-1) (mu = 1.0) were determined by a Stern-Volmer analysis. For trans-Cr(tet a)F(2+) in H(2)O, no energy transfer was observed, which implies that the rate constant is <<3 x 10(5) M(-1) s(-1). Because these energy-transfer reactions represent self-exchange energy transfer and are thus thermoneutral, we are able to analyze the results using Marcus theory and draw some conclusions about the relative importance of nuclear reorganization and electronic factors in the overall rate.