An improved synthesis of a water-soluble derivative of dipyrido[3,2-a:2',3'-c]phenazine (dppz) is reported. The structures of both dppz and the cation ethylene-bipyridyldiylium-phenazine dinitrate [[1][(PF(6))(2)]] have been obtained via X-ray crystallography. Metal complex derivatives of dppz are very well studied. However, using the water soluble [1][(NO(3))(2)], the nature of the interaction of a simple dppz unit with duplex DNA has been investigated for the first time. In both organic solvents and water, 1 displays unstructured luminescence, assigned to an intramolecular charge transfer. The emission is quenched on binding to natural and synthetic duplex DNA, including poly(dA).poly(dT). A variety of techniques reveal that the cation binds to DNA with an affinity comparable to those of many metal dppz complexes, via an intercalative binding mode.

The "DNA light switch" [Ru(phen) 2 (dppz)] 2+ (1; dppz = dipyrido[3,2-a:2',3'-c]phenazine, phen = 1,10-phenanthroline) has attracted particular attention, as it displays a huge luminescence enhancement (> 10 4 ) upon intercalation into DNA.[2] The excited states of such systems are insufficiently oxidizing to cleave DNA directly, and although they can generate singlet oxygen [3] -a species that can cause DNA damage and even some cleavage [4] -this process has low quantum yields, particularly for intercalated [Ru II (dppz)] systems, [5] and strand cleavage by secondary 1 O 2 oxidation is usually only fully accomplished by subsequent treatment with alkali or piperidine.[6] Ground-state [Ru(dppz)] systems in which the metal is in a higher oxidation state-generated by electrochemistry or flash-quench procedures-have been shown to produce direct frank cleavage. [6,7] However these later systems are not light switches. Previous studies revealed that the related Re I complex [Re(CO) 3 (py)(dppz)] + (2; py = pyridine) is capable of direct cleavage, but it possesses a greatly reduced binding affinity relative to that of 1. [8,9] Furthermore, 2 is not a true light switch: its weak p!p*-based emission in water shows a much lower enhancement (13) upon DNA binding [9] relative to 1 and its DNA-bound emission quantum yield is two orders of magnitude lower than that of 1.[10] Dinuclear [M(dppz)] systems are known. For example, NordØn and co-workers reported dinuclear [Ru II (dppz)] systems connected through dppz moieties which intercalate by a threading mechanism.[11] However, the construction of such enantiopure architectures from coordinatively saturated monomers is demanding and binding affinities are not greatly affected by chirality.We are exploring more-facile methods for the synthesis of oligomeric metallointercalators. [12,13] For example, by using achiral, coordinatively unsaturated [Ru(tpm)(dppz)(L)] 2+ units (tpm = tris(1-pyrazolyl)methane, L = N-donor ligand) with binding parameters comparable to that of 1, [14] we have developed a generalized method for the construction of bimetallic systems, the first example of which is [{Ru(tpm)-(dppz)} 2 (m-dpp [5])] 4+ (dpp[5] = 4,4'-dipyridylpentane), which binds to extended duplex sequences (> 6 base pairs).[12] This method has been extended to obtain the first hetero-dinuclear dppz complex.The Ru3+ (3) was synthesized from the known mononuclear complexes [7][8][9]13] [Ru(tpm)(dppz)(dpp [5])] 2+ and [ReCl(CO) 3 (dppz)] through the two-step method used to obtain [{Ru(tpm)(dppz)} 2 (m-dpp[5])] 4+ .[12]

The inhibition of FKBP5 mRNA expression by a selective GR antagonist is a potential clinical biomarker of GR antagonism.

No abstract