Pushing the limit: synthesis, photophysical and DNA binding studies of a NIR-emitting Ru(ii)-polypyridyl probe with ‘light switch’ behaviour

Abstract

The new Ru(II) polypyridyl complex 1 was synthesised using microwave irradiation from the new polypyridyl ligand 2 'DipyTAP', and its photophysical properties, and DNA binding abilities were investigated using various spectroscopic techniques; and 1 was shown to act as a 'NIR molecular light switch' for DNA with an emission window between 680 and 860 nm.Luminescent transition metal coordination complexes that possess DNA binding abilities have been the subject of growing interest in recent times by virtue of their potential use as DNA structure probes and cellular imaging agents.1,2 In particular, complexes such as Ru(II) and Cr(III)-polypyridyl complexes have been intensively studied owing to their tuneable photophysical and photochemical properties, which are governed by the nature of the polypyridyl ligands employed. 3 Moreover, complexes that function as molecular "light switches" for DNA, i.e. being nonluminescent in aqueous media but intensely luminescent upon binding to DNA, hold particular potential as biological imaging agents.4,5 However, most Ru(II)-polypyridyl complexes suffer from short wavelength absorption, with the metal-to-ligand charge transfer (MLCT) absorption maximum being shorter than 500 nm, and MLCT centred emission, usually shorter than 650 nm; a drawback for biological applications and for their potential use as cancer photo-therapeutics.6,7 Recently, we have initiated a research programme into the development of new polypyridyl ligands for application in biology, 8 and we have developed several examples that have been used in Ru(II)-polypyridyl complexes, as DNA targeting binders and imaging agents. 9 We have also employed these for conjugation to gold nanoparticles, 10 and have shown them to be excellent luminescent imaging probes, and formed mixed-lanthanide (Yb(III) and Nd(III)) transition-metal (f-d) cyclen-Ru(II) complexes as dual visible-and near-infrared (NIR)-emitting DNA sensors.11 With the view of developing this area even further, we have set out to generate novel polypyridyl ligands that could be used to generate long-wavelength excitation and emitting complexes. Inspired by the work of Meyer et al. and Zhou et al. who have recently developed a number of Ru(II)-polypyridyl complexes which exhibit 1 MLCT absorbance maxima as long as 550 nm and a singlet oxygen quantum yield as high as 0.43, 12 we set out to develop 1 based on 2, a new polypyridyl ligand, which we have named 'DipyTAP' as it contains two well established polypyridyl ligands within a single structure. We foresaw that through the use of a delocalized π-system the 2+ . Moreover, we observe that the 3 MLCT emission is fully quenched in aqueous media, similar to that seen for [Ru( phen) 2 (dppz)] 2+ and related structures, 13,14 but upon interaction of 1 with DNA the quenching process is perturbed resulting in an increase in the observed luminescence. To the best of our knowledge this is the first example of a Ru(II)-polypyridyl complex that can both act as a light switch for DNA, absorbing between 500 and 600 n...

Near-IR/Visible-Emitting Thiophenyl-Based Ru(II) Complexes: Efficient Photodynamic Therapy, Cellular Uptake, and DNA Binding

“…However, successive additions of DNA (0.00–90 μM) into Ru2 (2.33 μM) elicited slight emission enhancement by a factor of 1.32 along with a blue shift by 30 nm from 700 to 670 nm (see Figure b). This large DNA binding induced blue shift is not common in comparison to previously reported near-IR- − and visible-light-emitting Ru complex based DNA intercalators and groove binders and has not been observed for any DNA electrostatic binders. , This DNA binding induced spectral behavior of Ru2 is in sharp contrast to that of [Ru­(Hpip) 3 ] 2+ (Hpip = 2-phenylimidazo­[4,5- f ]­[1,10]-phenanthroline), which showed almost unchanged emission and UV–vis absorption spectral changes during the DNA titrations and was claimed to be a DNA electrostatic binder; the lack of intercalation or groove binding could be understood by the fact that [Ru­(Hpip) 3 ] 2+ contains three long and large Hpip ligands, which are difficult to accommodate efficiently in the DNA groove, although [Ru­(bpy) 2 (Hpip)] 2+ was evidenced to be a DNA intercalator . The aforementioned UV–vis absorption and emission spectral changes induced by binding of the DNA to Ru1 and Ru2 provide evidence that electrostatic DNA binding modes of these two complexes could be excluded, but their definite DNA binding modes with respect to intercalation or groove binding need further investigations.…”

Interaction of metal complexes with nucleic acids

“…An interesting study has shown that complex 47 acts as an efficient NIR molecular light switch. 57 On the basis of several spectroscopic techniques, it is suggested that this complex is inserted edgewise into the grooves of DNAalthough the authors did not discard the possibility of partial intercalation.…”

“…Complexes 55-60 are emissive and their luminescence is enhanced upon interaction with DNA -with some selectivity for quadruplex over duplex DNA. The cellular uptake of one of them (57) has been studied by real-time living cell microscopy, which showed it localises in the nucleus. 66 Another interesting feature of complex 57 is that its L stereoisomer has higher affinity towards quadruplex DNA than the D stereoisomer.…”

Photophysics of metal complexes

“…74 A Ru(phen) 2 complex of a dipyridyltetraazaphenanthrene acts as a NIR molecular light switch for DNA with emission at B780 nm in the presence of single stranded DNA. 75 Ru(bpy) 2 , Os(bpy) 2 and Ir(2-(p-tolyl)pyridine) 2 complexes of diarylamine-bpy-anthraquinone conjugate VI exhibit long-lived charge separated states with lifetimes of 80 ns to 1 ms upon excitation of the metallic chromophore. 78 [Ru(dcb) 2 ] complexes with a pyrene appended bpy ligand show dcb centred 3 MLCT emission at pH 0.…”