Synthesis, characterization and photodynamic activity of half-sandwich rhodium(III) complexes with curcuminoids.

Journal Pre-proof Synthesis,characterization,photodynamicactivityofhalf-sandwich rhodium(III)complexeswithcurcuminoids BaoquZhang,Jun’anXiao,XiaohuiWang,PeiyuanLi,WeiSu PII: S1572-1000(20)30403-8 DOI: https://doi.org/10.1016/j.pdpdt.2020.102049 Reference: PDPDT102049 Toappearin: PhotodiagnosisandPhotodynamicTherapy ReceivedDate: 12September2020 RevisedDate: 29September2020 AcceptedDate: 2October2020 Pleasecitethisarticleas:ZhangB,XiaoJ,WangX,LiP,SuW,Synthesis,characterization, photodynamicactivityofhalf-sandwichrhodium(III)complexeswithcurcuminoids, PhotodiagnosisandPhotodynamicTherapy(2020), doi:https://doi.org/10.1016/j.pdpdt.2020.102049 ThisisaPDFfileofanarticlethathasundergoneenhancementsafteracceptance,suchas theadditionofacoverpageandmetadata,andformattingforreadability,butitisnotyetthe definitiveversionofrecord.Thisversionwillundergoadditionalcopyediting,typesettingand reviewbeforeitispublishedinitsfinalform,butweareprovidingthisversiontogiveearly visibilityofthearticle.Pleasenotethat,duringtheproductionprocess,errorsmaybe discoveredwhichcouldaffectthecontent,andalllegaldisclaimersthatapplytothejournal pertain. © 2020PublishedbyElsevier. Synthesis, characterization, photodynamic activity of half-sandwich rhodium(III) complexes with curcuminoids Baoqu Zhanga, Jun’an Xiaoa, Xiaohui Wanga, Peiyuan Li*,b, Wei Su*,a, a Guangxi Key Laboratory of Natural Polymer Chemistry and Physics, Nanning Normal University, Nanning 530001, P. R. China. b College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China. A R T I C L E I N F O * Correponding author. E-mail address: lipearpear@163.com (Peiyuan Li) suwmail@163.com (Wei Su). Highlights f o  A series of novel half-sandwich rhodium(III) and iridium(III) complexes with curcuminoids (1-3) were o compared for anticancer photodynamic activity. r  showed remarkable phototoxic behavior against human HepG2 and SKOV3 cell lines. p  The complexes exhibited great potential as efficient photosensitizers for photodynamic therapy. - e r P A B S T R A C T Half-sandwich Cp*-Rh complexes containing curcuminoids ([Rh(η5-Cp*)(L)(Py)]PF6, 1–3, L = curcuminoid ligands L1–L3) were prepared, characterized and studied for anticancer activity. Complex 1 was structurally characterized byl single-crystal X-ray crystallography. Complex 3 presented excellent photodynamic anticancer effect in light (>400 nm) showing IC50 values of 7.5 and 4.3 μMa against HepG2, SKOV3 and HeLa, respectively, along with the 12.4, 7.9 and 4.7-fold lower toxicity in the dark. Confocal fluorescence images show that the complex primarily targeted mitochondrial localization. These results suggest that the complex 3 was a valuable agent with higher efficacy for chemotherapy and photodynamic therapy, which can achieve real-time image guidance in cancer therapy for the fluorescence of the complex as imaging signals. This investigation providesn a valuable route to design novel half-sandwich Cp*-Rh complexes with higher efficacy for photodynamic anticancer chemotherapy. Keywords: Curcuminoids: Half-sandwich complex Rhodium: X-ray strucyure r 1. Introduction u Dental Photodynamic therapy (PDT) is a type of non-invasive cancer treatment modality by involving the activation of a photosensitizer in visible light to gen o erate reactive oxygen (ROS) species . ROS including mainly singlet oxygen (1O2) that is generated via energy transfer from the triplet excited state of a photosensitizer to oxygen,[1] can selectively inactivate the light-exposed tumor cells and tissues.[2−4] Recently, different types of metal complexes have attracted increasing attention as photosensitizers for PDT with a diverse mechanism of action.[5-9] CurcumJin, an active ingredient of turmeric, is well-known for its medicinal values such as anticancer activity,[10] and display promising potential as photosensitizers in PDT.[11,12] However, the poor aqueous solubility and hydrolytic instability in buffer of physiological pH of 7.4 limit its therapeutic potential. Recent reports have shown that transition-metal complexes of curcumin possess stabilization and significantly increasing bioavailability. [13-16]Moreover, some of the complexes present promising photocytotoxicity in visible light against a variety of cancer cells.[17] Chakravarty et al. have demonstrated a platinum(II)-curcumin complex that implies dual action as a chemo- and phototherapeutic agent.[18] Renfrew’s group has reported a series of cobalt(III)-curcumin complexes that can be activated by visible light and used in PDT of cancer. [19] Organometallic half-sandwish ruthenium complexes, which show great structural variety and specific activities against different cancer cells, have attracted increasing attention in recent years.[20-21] Sadler et al. have reported the complexes, [(η6-arene)Ru(en)Cl]+ (en = ethylenediamine), which show the excellent cytotoxicity toward cancer cells.[22,23] Dyson's group has demonstrated the PTA complex of the general structure [(η6- arene)Ru(PTA)Cl2] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]-decane) with activity against metastases.[24,25] Moreover, some organometallic half-sandwish Ru(II) complexes have been employed in PDT application through the introduction of photosensitizer into the complexes. Juillerat- Jeanneret’s groups have reported a series of 5,10,15,20-tetra(4-pyridyl)porphyrin arene-ruthenium complexes and pentamethylcyclopentadienyl (Cp*) -iridium and -rhodium analogues as potential photosensitizing chemotherapeutic agents.[26,27] Wang et al. have demonstrated a series of arene-Ru(II) complexes for PDT application, in which the BODIPY units act the photodynamic action.[28,29] Previously, half-sandwish ruthenium and rhodium complexes contain curcumin and curcuminoids have been shown promising activity as anticancer agents.[30-33] However, the study using this kind of complexes as photosensitizer in PDT remains virtually unexplored. In this study, 1 half-sandwish rhodium complexes contain curcuminoids as the chelating ligand, and pyridine as the monodentate ligand. Thus, three half- sandwich RhIII compounds of the type [(η5-Cp*)Rh(curcuminoid)Z]PF6 (Z =pyridine) were synthesized and characterized. Their photophysical properties and phototoxicity toward cancer cells were investigated. Scheme 1. Curcuminoids and corresponding complexes. + O OH 9 10 5 [(Cp*)RhCl 2 ] 2 , NaOEt, EtOH N Rh O R 2 PF 6 - 4 2 O 7 3 1 AgPF 6 , Py R R 2 8 6 R 2 1 R R 1 1 L1: (cid:9)R = R = H 1 2 L2: R 1 = H, R 2 = F R 2 R 1 L3: R = R = OCH 1 2 3 1 - 3: L = L1, L2, L3 f o o 2. Results and discussion r 2.1. Synthesis and Characterization p Synthesis and Characterization. The complexes were synthesized by stirring [(Cp*)RhCl2]2 with the curcuminoids in a 2:1 mole ratio in ethanol at 45 ℃ (Scheme 1). All complexes were characterized using 1H NMR spectroscopy, high-resolution (HR)‐ESI‐MS and elemental analysis. In addition, crystal structure was obtained for compoun-d 1. The X-ray crystal structure of a Cp*-Rh complex 1 was determined using single‐crystal X‐ray diffraction analysis (Figure 1). The complex crystallized in the monoclinic space group I2. The crystallograephic data are shown in Table 1, and selected bond lengths and angles are listed in Table 2. In the molecular structure of the complex, Rh adopts the familiar ‘three-legged piano-stool’ geometry with the metal centre being coordinated by the aromatic Cp* ligand, a chelating O,O-ligand of curcuminoids and a pyridine. The Cp* r ligand is essentially planar, and the distance between the centroid of the Cp* ligand and the metal atom is 1.7597(5) Å. The bond distances around the metal atoms, the Ru─N bond lePngth is 2.1383(9) Å and the Ru─O bond lengths vary over a small range (2.0877(4)–2.1008(2) Å). All of the data are in agreement with similar compounds.30-34 The bidentate angles around the Rh atom, O1- Rh1-O2 [89.558(10)°], O1-Rh1-N1 [85.070(9)°] and O2-Rh1-N1 [86.311(11)°], are comparable to those of similar complexes.[34] Table 1. Crystal data and details of data collection for 1. Complex l 1 aformula C34H35F6NO2PRh Mr 737.51 crystal system monoclinic space group I2 na (Å) 19.461(4) b (Å) 11.6457(13) c (Å) 16.585(4) α (°) 90.00 r β (°) 114.28(3) γ (°) 90.00 uV (Å3) 3426.0(12) Z 4 Dc(Mg/m3) 1.430 F(000) 1504 o μ (mm-1) 0.608 Rint 0.0474 reflns collected 11985 J reflns ind 7007 GOF (S) 1.020 R1/wR2 [I ≥ 2σ (I)] 0.0704/ 0.1677 R1/wR2 [all data] 0.1219/ 0.2176 Table 2. Selected bond lengths (Å), angles (deg) in 1. Complex 1 2 Rh1-centroid 1.7597(5) Rh1-O1 2.1008(2) Rh1-O2 2.0877(4) Rh1-N1 2.1383(9) O1-Rh1-O2 89.558(10) O1-Rh1-N1 85.070(9) O2-Rh1-N1 86.311(11) 2.2. Photophysical properties The absorption and emission spectra of 1–3 in DMSO are presented in Figure 2, and the basic photophysical properties of 1–3 are shown in Table 3. Complex 1 and 2 exhibit the similar wide absorption spectra in which the absorption maximum is found at 398 nm. Upon excitation at λ = 398 nm in the same solvent, these two complexes give same emissions at λ = 474 nm with fluorescence quantum yields (Φ F) of 0.017 and 0.015, respectively. Compared with 1 and 2，the absorption band of 3 have a red shift with λmax = 442 nm and the emissions in λ = 542 with the Φ F of the 3 is higher at 0.116. f o o r p - e r P l a Figure 2. UV-vis (A) and emission (B) spectra for 1-3 in DMSO. n Figure 1. ORTEP plots of 1, the solvent molecules and anion have been omitted for clarity. r u Table 3. o Electronic absorption and photophysical properties of 1-3. Compound λabs (nm) [log ε] λem a (nm) ΦF b ΦΔc J1 360 [3.47], 398 [3.45], 423 [3.42], 450 [3.33] 474 0.017 0.109 2 360 [3.44], 398 [3.45], 423 [3.40], 450 [3.27] 474 0.015 0.033 3 471sh [3.58], 4423 [3.65], 467 [3.64] 542 0.116 0.205 a Excited at 395 nm. Relative to porphin and rhodamine 6G in DMSO as the reference (Φ F = 0.92). c Relative to tetraphenylporphyrin in CHCl3 as the reference ( Φ Δ = 0.55). 3 f o o r Figure 3. UV‐Vis absorbance spectra of 3 in DMSO/H2O (A) before and (B) after irradiation (λ > 400 nm) with light (0–180 min). p The singlet oxygen (1O2) quantum yields of complexes 1–3 were determined using a steady-state method, according to a method described previously.[35] 1,3-diphenylisobenzofuran (DPBF) are used as the qu - enching agent, and tetraphenylporphyrin (H2TPP) are taken as the standard (Φ Δ = 0.55 in CHCl3). All of the complexes produce 1O2 efficiently with values in the range of 0.015–0.205 (Table 1). Herein, 3 shows the highest 1O2 quantum yields (Φ Δ = 0.205), whiche indicates the methoxy group on curcuminoid ligand might has positive affect on improving the 1O2 quantum yields of this kind of complex. The solution stability of complexes was studied by monitoring their UV‐Vis absorbance spectra before and after irradiation. The time‐dependent absorption spectra of 3 being monitored for 180 r min, a slight decrease is observed for the intensity of the absorption bands at 432 nm, which suggests the occurrence of slow hPydrolysis that is important in the biological functions of these complexes.[36] Nevertheless, as shown in Figure 3B, an obvious intensive decrease is found after irradiation (λ > 400 nm), indicating that the irradiation facilitates the hydrolysis of the complex and plays an essential role in the improvement of their biological activity. Table 4. IC50 values (μM) and phototoxicity index a (PI). l a HepG2 SKOV3 HeLa Compound Dark Light PI Dark Light PI Dark Light PI n 1 > 100 > 100 - > 100 31.9 ± 0.7 > 3.4 > 100 > 100 - 2 > 100 > 100 - > 100 > 100 - > 100 > 100 - 3 93 ± 2.5 r7.5 ± 0.5 12.4 34 ± 6.0 4.3 ± 0.9 7.9 70 ± 6.7 15 ± 1.0 4.7 a Dark IC50/Light IC50. u o J 4 2.3. Photocytotoxicity The dark and light cytotoxicities of complexes 1–3 were evaluated against HepG2 liver cancer cells, SKOV3 ovarian cell lines and HeLa cervical cancer cells by the WST-8 assay. Cells were incubated with the Rh complexes for 4 h in the dark, then exposed to light irradiation (>400 nm) for 30 min, and followed by 20 h incubation in the dark. For comparison purposes, dark toxicity measurements were conducted in parallel. The complexes exhibit low cytotoxicity against the three carcinoma cell lines in dark. The IC50 values of complex 1 and 2 are deemed inactive (>100μ M), and 3 shows the moderate activity with the IC50 value of 93 ± 2.5, 34 ± 6.0 and 70 ± 6.7 μM against HepG2, SKOV3 and HeLa cancer cells lines, respectively. After irradiation with light for 30 min, no increase in cell death was observed for samples dosed with 1 and 2 in these cells except complex 1 shows IC50 value of 31.9 ± 0.7 μM toward SKOV3 cells. In particular, 3 exhibits enhanced cytotoxicities toward the carcinoma cells upon irradiation with light. It possesses IC50 values of 7.5 ± 0.5, 4.3 ± 0.9 and 15 ± 1.0 μM, which is 12.4, 7.9 and 4.7 times more cytotoxic than that in dark, respectively, showing promising potentials as PDT agents. The highest phototoxicity of 3 in these complexes under the conditions tested might be attributed to the combined action of its higher 1O2 quantum yield as well as the intrinsic biological effect of the Cp*-Rh complex. 2.4. Cell Uptake in Vitro Fluorescence microscopic images show cytoplasmic localization of the complex in SKOV3 cells, which is essential because it asserts direct f damage on cellular metabolism and compels the cell to collapse.[18] As shown in Figure 4, after incubation with 3 (0.08 mM) at 37 ℃ for 4 h, the green fluorescence is observed in SKOV3 cells cells on 488 nm excitation, indicating that the complex was suoccessfully endocytosed into tumor cells. The merge of Bright-field and Dark-field images (Figure 4) confirms that 3 mainly located inside the cytoplasm without obvious nuclear uptake, suggesting that the complex is targeted mitochondria as is observed for the PDT drug Photofrin.[37,38] Antitumor drugs localizing in the o mitochondria can avoid the deactivation pathway associated with the nuclear DNA targeting agents by nuclear excision repair (NER) mechanism.[39] r p - e Figure 4. Confocal fluorescence images of SKOV3 cells treated with complex 3. (A) Bright-field. (B) Dark-field. (C) Merge. r 3. Conclusions This work presents a structurally characterized Cp*-Rh cPomplex containing curcuminoid showing light-induced (>400 nm) cytotoxicity in HepG2, SKOV3 and HeLa cancer cells. Complex 3 shows remarkable phototoxic activity against HepG2 and SKOV3 cancer cells, with IC50 = 7.5 and 4.3 μM (λirr > 400 nm), respectively, as well as the 12.4 and 7.9-fold lower toxicity in the dark. This indicates the potential of 3 as a dual- action half-sanwish anticancer agent for combination therapy. The emissive complex was employed for cellular imaging, which showed primarily mitochondrial localization. This investigation demonstrates that the complex 3 can be employed as photosensitizers for chemotherapy and photodynamic therapy. Moreover, the fluorescence of lthe complex could act as imaging signals, which shows the potential to achieve real-time image guidance in cancer therapy. a 4. Experimental section 4.1 Materials and methods n [(Cp*)RhCl2]2 were purchased from Sigma Co. All of the curcuminoid analogues (L1-L3) were prepared by literature methods[14]. All reagents and solvents were of high purity and used without further purification. NMR spectra were recorded on a Bruker AV-300 spectrometer at working frequencies 300. Chemical shifts are expressed in parts per million (δ) values and coupling constants (J) in Hertz. Mass spectra for the complexes r were recorded on a Waters UPLC XEVO G2 TOF mass spectrometer using electrospray ionization probe. Elemental analyses were carried out using an Elementar Vario uEL Cube. UV-vis absorption spectra were measured on a Cary 100 UV-vis spectrophotometer (Agilent Technologies, Inc., Australia). 4.2 Synthesis of complexes Synthesis of [Roh(η5-Cp*)(L1)(Py)]PF6 (1). [Rh(η5-Cp*)Cl2]2 (30.9 mg, 0.05 mmol), L1 (27.6 mg, 0.1 mmol) and C2H5ONa (10.2 mg, 0.15 mmol) were dissolved in 6 mL of ethanol. The reaction mixture was stirred at 45 ℃ for 5 h, and AgPF6 (25.3 mg, 0.1 mmol) was added. The reaction mixture was stirred for 2 h and filtered to remove AgCl. Pyridine (8 μL, 0.1 mmol) was finally added to the filtrate, which was stirred for 24 h at J 45 ℃. Removal of the solvent gave a orange solid which was further purified by recrystallization from CH2Cl2 and hexane. Yield: 34 mg, 46%. HR- ESI-MS (MeOH) m/z [Found (Calcd)]: 513.1277 (513.1301) (100%) [Rh(η5-Cp*)(L1)]+. 1H NMR (300 MHz, DMSO-d6) δ: 8.551 (d, 2H, J = 5.2 Hz, o-H of py), 8.068 (t, 1H, J = 7.6 Hz, p-H of py), 7.784 (d, 2H, J = 15.8 Hz, C(4,4’)H of L1), 7.714 (d, 4H, J = 5.8 Hz, C(6,6’;10,10’)H of L1), 7.656 (m, 2H, m-H of py), 7.445(m, 6H, C(7,7’;8,8’;9,9’)H of L1), 6.854 (d, 2H, J = 15.8 Hz, C(3,3’)H of L1), 5.570 (s, 1H, C(1)H of L1), 1.612 (s, 15H, η5-Cp*) ppm. Anal. Calcd for C34H35F6NO2PRh·1/4H2O: C, 55.03; H, 4.82; N, 1.89; Found: C, 55.01; H, 4.77; N, 1.83. [Rh(η5-Cp*)(L2)(Py)]PF6 (2). The synthesis was performed as for 1. Yield 38 mg, 49%. HR-ESI-MS (MeOH) m/z [Found (Calcd)]: 549.1100 (549.1113) (100%) [Rh(η5-Cp*)(L2)]+. 1H NMR (300 MHz, DMSO-d6) δ: 8.537 (d, 2H, J = 5.1 Hz, o-H of py), 8.066 (t, 1H, J = 7.6 Hz, p-H of py), 7.778 (m, 6H, C(4,4’;6,6’;10,10’)H of L2), 7.652 (m, 2H, m-H of py), 7.289 (t, 4H, J = 8.8 Hz, C(7,7’;9,9’)H of L2), 6.806 (d, 2H, J = 15.8 Hz, C(3,3’)H of L2), 5.521 (s, 1H, C(1)H of L2), 1.607 (s, 15H, η5-Cp*) ppm. Anal. Calcd for C34H33F8NO2PRh·1/2CH2Cl2: C, 50.78; H, 4.20; N, 1.72; Found: C, 50.98; H, 4.21; N, 1.80. [Rh(η5-Cp*)(L3)(Py)]PF6 (3). The synthesis was performed as for 1. Yield 52 mg, 61%. HR-ESI-MS (MeOH) m/z [Found (Calcd)]: 633.1705 (633.1724) (100%) [Rh(η5-Cp*)(L3)]+. 1H NMR (300 MHz, DMSO-d6) δ: 8.534 (d, 2H, J = 5.1 Hz, o-H of py), 8.066 (t, 1H, J = 7.5 Hz, p-H of py), 7.695 (d, 2H, J = 15.6 Hz, C(4,4’)H of L3), 7.653 (m, 2H, m-H of py), 7.286 (s, 2H, C(10,10’)H of L3), 7.258 (d, 2H, J = 8.5 Hz, C(6,6’)H of L3), 7.023 (d, 2H, J = 8.3 Hz, C(7,7’)H of L3), 6.736 (d, 2H, J = 15.6 Hz, C(3,3’)H of L3), 5.488 (s, 1H, C(1)H of L3), 3.823(d, 12H, J = 4.8 Hz, -OCH3 of L3), 1.605 (s, 15H, η5-Cp*) ppm. Anal. Calcd for C38H43F6NO6PRh·1/2H2O: C, 52.66; H, 5.12; N, 1.62; Found: C, 52.62; H, 5.14; N, 1.52. 4.3 X-ray Crystallographic Determination 5 The reflection data were collected on a Bruker SMART CCD instrument by using graphite monochromatic Mo Kα radiation (λ = 0.71073 Å) at room temperature. A semiempirical absorption correction by using the SADABS program was applied, and the raw data frame integration was performed with SAINT[31]. The crystal structures were solved by the direct method using the program SHELXS-97[32] and refined by the full- matrix least-squares method on F2 for all non-hydrogen atoms using SHELXTL-97[33] with anisotropic thermal parameters. The details of the crystal data were summarized in Table 1, and selected bond lengths and angles for 1 are listed in Table 2. Crystallographic data for the structural analysis have been deposited with the Cambridge Crystallographic Data Center. CCDC reference numbers: 1979514. 4.4 1O2 measurement Measurements were taken at 420 nm excitation in air-saturated solutions at room temperature with TPP (Φ Δ = 0.55, λex = 400 nm) in CHCl3 as references. The maximal absorption of the complexes at corresponding wavelength was generally kept between 0.01 and 0.3. 4.4 Phototoxicity. HepG2 (human liver carcinoma), SKOV3 (human ovarian carcinoma) and HeLa (human cervical carcinoma) were obtained by Commerce. Photo and dark toxicity of the complexes were evaluated by WST-8 (water-soluble tetrazolium salts) assay using CCK-8 reagent. The cells (2×104 cells per well) were seeded on a 96-well plate in 200 μL of culture medium and incubated for 1 day at 37 °C in a 5% CO2 atmosphere. Then 100 μ L of micelle solutions prepared in culture medium at 5 μM complexes were added in each well. After 4 h incubation, the cells were exposed to a 300 W xenon lamp after passing through a color glass filter cut-on 400 nm for 30 min at the power density of 30 mW/cm2, followed by 20 h f incubation. Then 100 μL of fresh culture medium and 10 μL of CCK-8 reagent were added in each well and the cells were incubated for 3 h. Finally, the absorbance (A) at 450 nm was measured using a Thermo Scientific Multiskan MK3. o 4.5 Confocal Microscopic Imaging Confocal microscopy imaging of living cells Human SKOV3 cells were grown in a humidified at mosphere containing 5% CO2 at 37 ◦C in o DMEM medium supplemented with 10% FBS and 1% penicillin-streptomycin solution. SKOV3 cells were seeded onto 35 mm glass bottom culture dishes for 24 h after the concentration reached 5×105 cells/mL. Cells in exponential growth phase were used for experiment (2×104 cells/well) and seeded to 96-well plates for overnight. Then,the cells were incubated with the complexes (500r μg/mL) for another 4 h and then washed with phosphate buffered solution (pH 7.5) three times. Finally, the confocal microscopy imaging experiments were conducted (20 × objective). 5. Acknowledgements p This research was supported by the National Natural Science Foundation of China (21761006, 51961009), Natural Science Foundation of Guangxi Province (2018GXNSFAA281345, 2017GXNSFAA198335), “BAGUI Scholar” Program of Guangxi Province of China, Natural Science - Foundation of Guangxi University of Chinese Medicine (2017JQ001), Guangxi First-class Discipline: Chinese Materia Medica (Scientific Research of Guangxi Education Department [2018] No. 12) (2019XK135), Project of eGuangxi Key Laboratory of Zhuang and Yao Ethnic Medicine (GXZYZZ2019-4). r P l a n r u o J 6 References [1] J. D. Knoll, C. Turro, Coordin. Chem. Rev. 2015, 282–283, 110–126. [2] Y. Huang, F. Qiu, L. Shen, D. Chen, Y. Su, C. Yang, B. Li, D. Yan, X. Zhu, ACS Nano 2016, 10, 10489−10499. [3] L. Zhou, L. Zhou, X. Ge, J. Zhou, S. Wei, J. Shen, Chem. Commun. 2015, 51, 421-424. [4] Y.-F. Ding, S. Li, L. Liang, Q. Huang, L. Yuwen, W. Yang, R. Wang, L.-H. Wang, ACS Appl. Mater. Interfaces 2018, 10, 9980−9987. 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