Polypyridyl Co^II‐Curcumin Complexes as Photoactivated Anticancer and Antibacterial Agents

Abstract

Four new Co II complexes, [Co(bpy) 2 (acac)]Cl (1), [Co-(phen) 2 (acac)]Cl (2), [Co(bpy) 2 (cur)]Cl (3), [Co(phen) 2 (cur)]Cl (4), where bpy = 2,2'-bipyridine (1 and 3), phen = 1,10-phenanthroline (2 and 4), acac = acetylacetonate (1 and 2), cur = curcumin monoanion (3 and 4) have been designed, synthesized and fully characterized. The X-ray crystal structures of 1 and 2 indicated that the CoN 4 O 2 core has a distorted octahedral geometry. The photoactivity of these complexes was tuned by varying the π conjugation in the ligands. Curcumin complexes 3 and 4 had an intense absorption band near 435 nm, which made them useful as visible-light photodynamic therapy agents; they also showed fluorescence with λ em � 565 nm. This fluorescence was useful for studying their intracellular uptake and localization in MCF-7 breast cancer cells. The acetylacetonate complexes (1 and 2) were used as control complexes to understand the role of curcumin. The white-light-triggered anticancer profiles of the cytosol targeting complexes 3 and 4 were investigated in detail. These non-dark toxic complexes displayed significant apoptotic photo-cytotoxicity (under visible light) against MCF-7 cells through ROS generation. The control complexes 1 and 2 did not induce significant cell death in the light or dark. Interestingly, 1-4 produced a remarkable antibacterial response upon light exposure. Overall, the reported results here can increase the boundary of the Co II -based anticancer and antibacterial drug development.

Density Functional Theory-Guided Photo-Triggered Anticancer Activity of Curcumin-Based Zinc(II) Complexes

“…47,49 Curcumin complexes (2, 3) showed a sharp IR band near 1515 cm −1 corresponding to the α,β-unsaturated ketone's C�C bonds. 47,49 The HRMS of complexes 1−3 in MeOH showed a molecular ion peak corresponding to the [M − Cl] + species (Figures S13−S15). Complexes 2 and 3 showed a strong absorption band near 430 nm in 10% aq.…”

“…79 As the anticancer activities of 2 and 3 were found to improve remarkably on light exposure, these complexes would probably induce apoptotic cell death by ROS generation as is reported for numerous curcumin-metal complexes. [47][48][49]61 The basic concept of PDT also relies on photosensitizer-induced ROS generation at the target cancer site because the photosensitizers have the ability to generate singlet oxygen ( 1 O 2 ) via a type-II energy transfer pathway upon light excitation. 16 Our computational study revealed that singlet−triplet splitting of complexes 2 and 3 is sufficient to produce 1 O 2 (Figure 2(e)).…”

“…For the above-mentioned Zn­(II)-curcumin complexes, anticancer activities were mainly derived from the inherent anticancer potential of curcumin. − Curcumin (1,7-bis­(4-hydroxy-3-methoxy­phenyl)-1,6-hepta-diene-3,5-dione), a natural product, displays anticancer activity by reducing the activity of NF-kB (a key protein that controls DNA transcription, cytokine production, and cell survival) and escalating the activity of tumor suppressor protein p53. , However, the low hydrolytic stability and bioavailability of curcumin restrict its huge potential as an anticancer drug . It has been established that the metal complexation of curcumin increases its stability and bioavailability. − Moreover, curcumin is reported as a good photosensitizer due to its efficient singlet oxygen generation ability under visible light . Therefore, in recent years, several curcumin-based metal complexes have been reported for PDT. − ,− Several curcumin complexes of V­(IV), Fe­(III), Co­(II), Co­(III), Pt­(II), Ru­(II), Ir­(III), Os­(II), Rh­(III), etc.…”

Chelated O2BOH2– or Chelated O2CO2–: An Isoelectronic Conundrum

“…T he coordination chemistry of oxyanions as ligands in "classical" coordination complexes has been extensively studied, and a large number of transition metal complexes containing ligands such as CO 3 3−14 However, several features of the reported synthesis and characterization led us to question the identity of the isolated complex. First, the reaction was carried out under aerobic conditions; air oxidation of solutions of Co(II) in the presence of amine ligands is often facile, and while Co(II) complexes containing two bipy ligands have been isolated under aerobic conditions, 15,16 oxidation to Co(III) cannot be excluded. A Co(III) oxidation state was further supported by examination of the reported X-ray structure; the Co−N bond lengths, which range from 1.913 to 1.944 Å, are consistent with those found in Co(III) complexes containing two bipy ligands 17,18 and are significantly shorter than those in analogous Co(II) complexes (d Co−N ∼ 2.1 Å).…”

“…Therefore, the recent report by Pan and co-workers of only the second structurally characterized example of chelated hydrogenborate in the Co­(II) complex [Co­(bipy) 2 O 2 BOH]·[B 5 O 6 (OH) 4 ]·H 3 BO 3 ·H 3 O·H 2 O (bipy = 2,2′-bipyridine) was of interest, given our extensive work on the coordination chemistry of oxyanions. − However, several features of the reported synthesis and characterization led us to question the identity of the isolated complex. First, the reaction was carried out under aerobic conditions; air oxidation of solutions of Co­(II) in the presence of amine ligands is often facile, and while Co­(II) complexes containing two bipy ligands have been isolated under aerobic conditions, , oxidation to Co­(III) cannot be excluded. A Co­(III) oxidation state was further supported by examination of the reported X-ray structure; the Co–N bond lengths, which range from 1.913 to 1.944 Å, are consistent with those found in Co­(III) complexes containing two bipy ligands , and are significantly shorter than those in analogous Co­(II) complexes ( d Co–N ∼ 2.1 Å). , Similarly, the reported B–O bond lengths are almost exactly the same as the C–O distances found in Co­(III) amine complexes containing chelated carbonate. ,, Finally, we were concerned about the presence of an H 3 O + ion in the structure.…”