A Multifunctional Light Switch: DNA Binding and Cleavage Properties of a Heterobimetallic Ruthenium–Rhenium Dipyridophenazine Complex

Abstract

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]

Exploitation of Luminescent Organometallic Rhenium(I) and Iridium(III) Complexes in Biological Studies

“…The mitochondria-specificity has been confirmed with co-localisation experiments using TMRE, which is known to accumulate in mitochondria. The first class of luminescent biotinylation reagents, derived from rhenium(I) polypyridine complexes [Re(N^N)(CO) 3 (py-biotin-NCS)] + (24), have been reported by Lo and co-workers [62]. To investigate the amine-specific reactivity + (25).…”

“…Thus, initially at least, the complex functions as a monointercalating system and the second rhenium centre may be free to interact with other DNA duplexes (interstrand binding). Recently, a related heterobimetallic complex [{Ru(tpm)(dppz)(m-dpp [5])(CO) 3 Re(dppz)}] 3+ (5) has been isolated that possesses both DNA-light switch and photocleavage properties [24].…”

Homo‐ and Heteroleptic Phototoxic Dinuclear Metallo‐Intercalators Based on RuII(dppn) Intercalating Moieties: Synthesis, Optical, and Biological Studies

“…[30,31] These units have provided more facile methods toward the synthesis of oligomeric metallo-intercalators. [32][33][34] Given the proven therapeutic potential of the Ru II dppn-moiety, we set out to synthesize dinuclear systems that incorporate this unit and, for the first time, the syntheses of both dinuclear homoleptic (Ru II dppn) and heteroleptic (Ru II (dppz)/Ru II (dppn)) complexes are described. In the initial studies reported herein we also compare the photophysical and cell-based biological properties of these new complexes with their Ru II dppz analogues.…”

Chromo- and Fluorogenic Organometallic Sensors

“…Recent developments include the consideration of bimetallic complexes, such as 13e, where a hypsochromic shift in both the MLCT and IL transitions when added to buffered DNA [124]. Studies with the hetero-dinuclear complex 13f reveal energy transfer between the Re(I) and the Ru(II) centres, and a light-switch behaviour in the emission on the introduction of DNA [125].…”