2D NMR spectroscopy has been used to determine the metal configuration in solution of three complexes, viz. [(η⁶-p-cymene)Ru(L*)Cl] (1) and [(η⁶-p-cymene)Ru(L*)(L′)] (C1O₄) (L′ = H₂O,2; PPh₃,3), where L* is the anion of (S)-(l-phenylethyl)salicylaldimine. The complexes exist in two diastereomeric forms in solution. Both the (R_Ru,S_c)- and (S_Ru,S_c)-diastereomers display the presence of attractive CH/π interaction involving the phenyl group attached to the chiral carbon and the cymene ring hydrogens. This interaction restricts the rotation of the C*-N single bond and, as a result, two structural types with either the hydrogen atom attached to the chiral carbon (C*) or the methyl group attached to C* in close proximity of the cymene ring protons get stabilized. Using 2D NMR spectroscopy as a tool, the spatial interaction involving these protons are studied in order to obtain the metal configuration(s) of the diastereomeric complexes in solution. This technique has enabled us to determine the metal configuration as (R_Ru,S_c) for the major isomers of 1–3 in solution.

The chemistry of ternary and binary copper(II) complexes showing efficient visible light-induced DNA cleavage activity is summarized in this article. The role of the metal in photo-induced DNA cleavage reactions is explored by designing complex molecules having a variety of ligands. Ternary copper(II) complexes with amino acid like L-methionone or L-lysine and phenanthroline base are efficient photocleavers of DNA. Complexes of formulation [Cu(Lⁿ)(phen)](C1O₄) with NSO-donor Schiff base (HLⁿ) and NN-donor heterocyclic base 1,10-phenanthroline (phen) show significant cleavage of super-coiled (SC) DNA on exposure to red light at ≈ 700 nm. Thed-d and CT electronic bands of the copper(II) complexes play important roles in DNA cleavage reactions. The mechanistic pathways are found to be dependent on the types of ligands present in the copper(II) complexes and the photo-excitation energy. While UV exposure generally proceeds via a type-II process forming singlet oxygen as the reactive species, red-light exposure leads to DNA cleavage following different mechanistic pathways, viz. type-I, type-II and photo-redox pathways. Ternary copper(II) complexes with phen as DNA binder and Schiff base with a thiomethyl group as photosensitizer, cleave SC DNA to its nicked circular (NC) form in a type-II process in red-light. The binary complex [Cu(dpq)₂(H₂0)](C10₄)₂ (dpq, dipyridoquinoxaline) cleaves DNA by photo-redox pathway at 694 nm. The binuclear complex [Cu_II²(RSSR)₂], where H₂RSSR is a Schiff base derived from 2-(thioethyl)salicylaldimine, cleaves SC DNA at 632.8 nm (CW He-Ne laser) and 694 nm (ruby laser) involving sulphide (type-I process) and hydroxyl radicals (photo-redox pathway) as the reactive species.

Binuclear complexes [Cu(𝜇-RSSR)]₂ (1) and [M₂(𝜇-PDS)(H₂O)]₂ (M = Cu(II), 2; Fe(II), 3), where H₂RSSR is a reduced Schiff base derived from 2-(thioethyl)salicylaldimine having a disulphide moiety and H₂PDS is derived from dimerization of D-penicillamine, have been prepared, structurally characterized, and their photo-induced DNA cleavage activity studied. The crystal structure of 1 shows the complex as a discrete binuclear species with each metal in a CuN2O2 square-planar geometry (Cu…Cu, 6.420 Å). The tetradentate RSSR^2- acts as a bridging ligand. The sulphur atoms in the disulphide unit do not interact with the metal ions. Complexes 1-3 do not show any DNA cleavage activity in darkness. The copper(II) complexes exhibit chemical nuclease activity in the presence of 3-mercaptopropionic acid. Cleavage of supercoiled DNA has been observed in UV-A light of 365 nm for 1 and red light of 647.1 nm for both 1 and 2 in air. Mechanistic data reveal the involvement of the disulphide unit as photosensitizer generating hydroxyl radicals ($^{\bullet}$OH) as the reactive species. Photo-induced DNA cleavage in red light seems to involve sulphide radicals in a type-I process and hydroxyl radicals. The dicopper(II) complexes show significant anaerobic photo-induced DNA cleavage activity in red light under argon following type-I pathway without involving any reactive oxygen species.

Lanthanide complexes have recently received considerable attention in the field of therapeutic and diagnostic medicines. Among many applications of lanthanides, gadolinium complexes are used as magnetic resonance imaging (MRI) contrast agents in clinical radiology and luminescent lanthanides for bioanalysis, imaging and sensing. The chemistry of photoactive lanthanide complexes showing biological applications is of recent origin. Photodynamic therapy (PDT) is a non-invasive treatment modality of cancer using a photosensitizer drug and light. This review primarily focuses on different aspects of the chemistry of lanthanide complexes showing photoactivated DNA cleavage activity and cytotoxicity in cancer cells. Macrocyclic texaphyrin-lanthanide complexes are known to show photocytotoxicity with the PDT effect in near-IR light. Very recently, non-macrocyclic lanthanide complexes are reported to show photocytotoxicity in cancer cells. Attempts have been made in this perspective article to review and highlight the photocytotoxic behaviour of various lanthanide complexes for their potential photochemotherapeutic applications.

Iron(II) complexes of polypyridyl ligands (B), viz. [Fe(B)₂]Cl₂ (1 and 2) of N, N, N-donor 2-(2-pyridyl)-1,10-phenanthroline (pyphen in 1) and 3-(pyridin-2-yl)dipyrido[3,2-a:2’,3’-c]phenazine (pydppz in 2), are prepared and characterized. They are 1:2 electrolytes in aqueous DMF. The diamagnetic complexes exhibit metal to ligand charge transfer band near 570 nm in DMF. The complexes are avid binders to calf thymus DNA giving binding constant (𝐾_b) values of ∼10⁶ M⁻¹ suggesting significant intercalative DNA binding of the complexes due to presence of planar phenanthroline bases. Complex 2 exhibits significant photocytotoxicity in immortalized human keratinocyte cells HaCaT and breast cancer cell line MCF-7 giving IC₅₀ values of 0.08 and 13 𝜇M in visible light (400–700 nm). Complex 2 shows only minor dark toxicity in HaCaT cells but is non-toxic in dark in MCF-7 cancer cells. The light-induced cellular damage follows apoptotic pathway on generation of reactive oxygen species as evidenced from the dichlorofluorescein diacetate (DCFDA) assay.

Ternary copper(II) complexes of salicylaldehyde-histamine Schiff base (HL) and pyridyl ligands, viz. [Cu(bpy)(L)](ClO₄) (1) and [Cu(dppz)(L)](ClO₄) (2), where bpy is 2,2′-bipyridine (in 1) and dppz is dipyrido[3,2-a:2′,3′-c]phenazine (in 2), were synthesized, characterized and their DNA binding, photo-activated DNA cleavage activity and photocytotoxicity studied. The 1:1 electrolytic one-electron paramagnetic complexes showed a d-d band near 670 nm in aqueous DMF (1:1 v/v). The crystal structure of complex 1 showed the metal in CuN₄O distorted square-pyramidal geometry. Complex 2 intercalatively binds to calf-thymus (ct) DNA with a binding constant (𝐾_b) of ∼10⁵ M⁻¹. It exhibited moderate chemical nuclease activity but excellent DNA photocleavage activity in red light of 647 nm forming $^{\bullet}\text{OH}$ radicals. It showed remarkable photocytotoxicity in human cervical cancer cells (HeLa) giving IC₅₀ of 1.6 𝜇M in visible light (400-700 nm) with low dark toxicity. The photo-induced cell death is via generation of oxidative stress by reactive oxygen species.