Synthesis of luminescent rhodium(III) cyclometalated complex by sp2(C)–S bond activation: Application as catalyst in transfer hydrogenation of ketones and live cell imaging

Journal Pre-proof 2 Synthesis of luminescent rhodium(III) cyclometalated complex by sp (C)-S bond activation: Application as catalyst in transfer hydrogenation of ketones and live cell imaging Puspendu Roy, Deblina Sarkar, Paramita Ghosh, Chandan Kumar Manna, Nabendu Murmu, Tapan Kumar Mondal PII: S0022-2860(19)31633-3 DOI: https://doi.org/10.1016/j.molstruc.2019.127524 Reference: MOLSTR 127524 To appear in: Journal of Molecular Structure Received Date: 31 October 2019 Accepted Date: 02 December 2019 Please cite this article as: Puspendu Roy, Deblina Sarkar, Paramita Ghosh, Chandan Kumar Manna, Nabendu Murmu, Tapan Kumar Mondal, Synthesis of luminescent rhodium(III) 2 cyclometalated complex by sp (C)-S bond activation: Application as catalyst in transfer hydrogenation of ketones and live cell imaging, Journal of Molecular Structure (2019), https://doi.org /10.1016/j.molstruc.2019.127524 This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier. Journal Pre-proof Graphical Abstract Synthesis of luminescent rhodium(III) cyclometalated complex by sp2(C)-S bond activation: Application as catalyst in transfer hydrogenation of ketones and live cell imaging Puspendu Roy, Deblina Sarkar, Paramita Ghosh, Chandan Kumar Manna, Nabendu Murmu and Tapan Kumar Mondal A new fluorescent Rh(III) cyclometalated complex, [Rh(PPh ) (L)Cl] (1) has been synthesized 3 2 via sp2(C)-S bond activation of a thioether containing azo-phenol ligand (L-SCH CH ). The 2 3 complex exhibits low energy emission band at 682 nm with high emission quantum yield ( = 0.103). In presence of the complex a bright red fluorescence image of MCF-7 cell lines is observed under fluorescence microscope. Catalytic activity of complex 1 towards transfer hydrogenation of ketones is studied. Journal Pre-proof Synthesis of luminescent rhodium(III) cyclometalated complex by sp2(C)-S bond activation: Application as catalyst in transfer hydrogenation of ketones and live cell imaging Puspendu Roya,d, Deblina Sarkarb, Paramita Ghoshc, Chandan Kumar Mannaa, Nabendu Murmuc and Tapan Kumar Mondala* aDepartment of Chemistry, Jadavpur University, Kolkata-700032, India. bDepartment of Chemistry, Bagnan College, Howrah, W.B. 711303, India. cDepartment of Signal Transduction and Biogenis Amines, Chittaranjan National Cancer Institute, Kolkata- 700026, India dPresent address: Department of Chemistry, Netaji Nagar Day College, University of Calcutta, Kolkata – 700092, India. Abstract A new fluorescent Rh(III) cyclometalated complex, [Rh(PPh ) (L)Cl] (1) is synthesized via 3 2 sp2(C)-S bond activation of a thioether containing azo-phenol ligand (L-SCH CH ). The pseudo 2 3 octahedral geometry around rhodium is confirmed by single crystal X-ray diffraction method. Cyclic voltammogram of the complex exhibits a quasi-reversible oxidation couple with E of 1/2 0.74 V (∆E = 100 mV) along with a quasi-reversible reduction couple (E = -1.18 V, ∆E = 130 1/2 mV) in acetonitrile. The complex exhibits low energy emission band at 682 nm with emission quantum yield ( = 0.103) upon excitation at 583 nm. Cytotoxicity of the complex is studied by MTT method with human breast cancer cell lines and IC value is found to 18.5 M. In 50 presence of the complex (10 M) a bright red fluorescence image of MCF-7 cell lines is Journal Pre-proof observed under fluorescence microscope. Moreover, the complex acts as effective catalyst towards transfer hydrogenation of ketones. Key words: Rhodium(III) cyclometalated complex; C-S bond activation; Luminescence property; Transfer hydrogenation; Live cell imaging; DFT calculation. Corresponding author: Email: tapank.mondal@jadavpuruniversity.in 1. Introduction For the last few years, cyclometalated complexes of Rh(III) and Ir(III) are widely studied because of their outstanding photochemical, photophysical and redox properties [1,2]. They have wide applications as potential photocatalysts, photosensitizers and photomolecular devices [3,4]. The luminescent Ir(III) complexes are the most researched class of materials considering their extensive use as the emitters in organic light-emitting cells and diodes [5-7], sensors [8,9] and in cellular imaging [10,11]. But, similar type of Rh(III) complexes are rarely studied because of their poor photophysical properties [12,13]. In the last decades luminescent transition metal complexes have attracted considerable interest for application in biosensing and cellular imaging study [14]. Cellular imaging offers a unique approach for visualizing morphological details inside the cell. Although polyaromatic organic chromophores are most widely used as fluorescence probes in cellular imaging, luminescent metal complexes especially with heavy transition metals are better probes for bioimaging because of their superior photophysical properties Journal Pre-proof with high photostability and relatively long life time. They also exhibit significant Stokes shifts for easy separation of excitation and emission wavelengths. In recent years metal mediated C-S bond activation has witnessed a tremendous upsurge in catalytic reactions [15-17]. The platinum group metal mediated alkyl C(sp3)-S bond cleavage is widely studied in recent past [18-21], but metal mediated aryl C(sp2)-S bond activation and formation of cyclometalated complex is rarely studied [22-25]. Herein, we have synthesized luminescent rhodium(III) cyclometalated complex, [Rh(PPh ) (L)Cl] (1) via aryl C(sp2)-S bond 3 2 cleavage of thioether containing azo-phenol ligand (L-SCH CH ). The catalytic property of the 2 3 complex 1 towards transfer hydrogenation of ketones in i-PrOH was studied. In addition, the biocompatibility of the complex was checked with human breast cancer cell lines (MCF-7) by in vitro cytotoxicity assay using MTT. The cell bioimaging study was also carried out in MCF-7 cell lines. 2. Experimental section 2.1. Material and methods Bis(triphenylphosphine)rhodium(I)carbonyl chloride, [Rh(PPh ) (CO)Cl] and 2-aminothiophenol 3 2 were purchased from Sigma Aldrich. 4-Chloro-2-((2-(ethylthio)phenyl)diazenyl)phenol (L- SCH CH ) was prepared following the reported method [26]. Microanalytical data (C, H, N) 2 3 were collected on PerkinElmer 2400 CHNS/O elemental analyzer. Infrared spectra were taken on a RX-1 Perkin Elmer spectrophotometer with samples prepared as KBr pellets. 1H NMR spectra were recorded on Brucker 300 MHz instrument in CDCl . HRMS mass spectra were recorded on 3 Waters (Xevo G2 Q-TOF) mass spectrometer. Electronic spectra were taken on a PerkinElmer Lambda 750 spectrophotometer. Luminescence property was measured using Shimadzu RF-6000 Journal Pre-proof fluorescence spectrophotometer at rt (298 K). Cyclic voltammetric measurements were carried out using a CHI Electrochemical workstation. A platinum wire working electrode, a platinum wire auxiliary electrode and Ag/AgCl reference electrode were used in a standard three-electrode configuration. [n-Bu N][ClO ] was used as the supporting electrolyte in acetonitrile under N 4 4 2 atmosphere with scan rate of 50 mV/s. 2.2. Synthesis of [Rh(PPh ) (L)Cl] (1) 3 2 0.173 g (0.25 mmol) Rh(PPh ) (CO)Cl was dissolved in 10 mL acetonitrile. To it 10 mL 3 2 acetonitrile solution of 4-chloro-2-((2-(ethylthio)phenyl)diazenyl)phenol (L-SCH CH ) (0.073 g, 2 3 0.25 mmol) was added and the reaction mixture was refluxed for 12 h under N atmosphere to 2 yield a deep blue solution. The solvent was then removed under reduced pressure. The dried crude product was purified by using a silica gel (mesh 60-120) column. The blue band of 1 was eluted by 50% (v/v) ethyl acetate-petroleum ether mixture. On removal of the solvent under reduced pressure the pure complex 1 was obtained as a blue solid which was further dried under vacuum. Yield, 0.140 g (63%). Anal. Calc. for C H Cl N OP Rh: C, 64.52; H, 4.17; N, 3.13%; Found: C, 64.69; H, 48 37 2 2 2 4.09; N, 3.07%. IR data (KBr, cm-1): 1410 (N=N). 1H NMR data (CDCl , ppm): 7.97 (1H, s), 3 7.63 (2H, d, J = 7.2), 7.21-7.56 ppm (34H, m). UV-vis in acetonitrile (nm) (, M-1cm-1): 627 (6390), 583 (5637), 535 (sh.), 388 (sh.), 346 (sh.), 291 (25627).  in acetonitrile ( = 583 em ex nm): 682 nm. HRMS m/z, 893.7215 (M-H+). Cyclic voltammetry (in acetonitrile, scan rate 50 mV/s): E , 0.74 V (∆E = 100 mV) and E , -1.18 V (∆E = 130 mV). 1/2 1/2 2.3. X-ray crystallography Journal Pre-proof Single crystals of 1 were obtained by slow diffusion of n-hexane into dichloromethane solution of the complex. X-ray data were collected using an automated Bruker AXS Kappa smart Apex-II diffractometer equipped with an Apex-II CCD area detector using a fine focus sealed tube as the radiation source of graphite monochromated Mo K radiation ( = 0.71073 Å). Details of crystal analyses, data collection and structure refinement are summarized in Table 1. Reflection data were recorded using the  scan technique. The structure was solved and refined by full-matrix least-squares techniques on F2 using the SHELX-97 [27]. The absorption corrections were done by multi-scan (SHELXTL program package) and all the data were corrected for Lorentz, polarization effect. Hydrogen atoms were included in the refinement process as per the riding model. 2.4. Theoretical study All calculations were performed with Gaussian 09 program package [28] with the support of the Gauss View visualization program. Full geometry optimizations were carried out using the density functional theory (DFT) method at the B3LYP level for the compound [29,30]. All elements except rhodium were assigned 6-31+G(d) basis set. The LanL2DZ basis set with effective core potential (ECP) set of Hay and Wadt was used for rhodium atom [31-33]. Vertical electronic excitations based on B3LYP optimized geometries were computed using the time- dependent density functional theory (TDDFT) formalism [34-36] in acetonitrile using conductor- like polarizable continuum model (CPCM) [37-39]. 2.5. Procedure for catalytic transfer hydrogenation In a typical experiment the ketone (3 mmol), KOH (0.1 mmol), and rhodium(III) complex (1) (0.006 mmol) were added to 10 mL of i-PrOH, and the mixture was stirred at 80 °C in an inert atmosphere. The reaction was then monitored at various time intervals by the use of GC. After Journal Pre-proof the reaction was complete, i-PrOH was removed on a rotary evaporator, and the resulting semisolid was extracted with diethyl ether (5 × 10 mL). The extract was passed through a short column of silica gel. The column was washed with ∼100 mL of diethyl ether. All the eluates from the column were mixed, and the solvent from the mixture was evaporated off on a rotary evaporator. The resulting residue was dissolved in 2-3 mL of hexane. Conversions were determined by GC instrument equipped with a flame ionization detector (FID) using a HP-5 column of 30 m length, 0.53 mm diameter and 5.00 m film thickness. The column, injector and detector temperatures were 200, 250 and 250 ºC respectively. The carrier gas was N (UHP 2 grade) at a flow rate of 30 mL/min. The injection volume of sample was 2 L. The alcohols were identified by GC using undecane as an internal standard and each of the catalytic run was performed three times. 2.6. In vitro cell imaging 2.6.1. Cell Survivability assay Human breast cancer cell lines MCF-7 were evaluated for cytotoxicity with rhodium(III) complex, [Rh(PPh ) (L)Cl] (1). MCF-7 cell lines were obtained from National centre for cell 3 2 science, Pune, India and maintained in Minimum Essential Media Earle’s (MEM) (Gibco, life technologies) supplemented with 10% Fetal Bovine Serum (FBS) (Gibco, life technologies, USA) and stored at 37 °C in a humidified incubator under 5% CO atmosphere. Cells were 2 seeded in 96-well plates at a density of 5103 cells per well and cultured in CO incubator for 24 2 h. The cells were treated with increasing doses complex concentrations (5, 10, 20, 25, 30, 50, 75, 100) M, along with control. Complex 1 was dissolved in DMSO but the final concentration of DMSO while treatment of cells was maintained below 1%. After treatment for 24 h, Methyl tetrazolium dye (MTT) (5 mg/ml) solution was added to each well (10 L/well). The plates were Journal Pre-proof incubated in the dark at 37 C for 2 h. To each well 100 L DMSO was added and allowed to stand for 1 h in a vortex shaker. Cell viability determination was studied by recording absorbance at 570 nm for each well using a microplate reader (Tecan, infinite M200). Untreated cells were served as 100% viable. Linearly fitted plot between complex concentration and O.D value at 570 nm was generated for determination of IC value of the free receptor. Concentration of the 50 complex resulting in 50% death after 24 h treatment was obtained as the IC value. 50 2.6.2. Live cell imaging Cultured cells were then grown on 22×22 mm glass cover slip placed on the bottom of six well plates and treated with 10 µM of complex for 12 h. The selected dose (10 µM) was less than LD which was found to be 18.53 µM. After 12 h, media were discarded and 500 µl methanol 50 added, kept for 15 min for fixation. Finally the cells were washed with 0.5 % Phosphate buffer saline Tween (PBST) twice and then with 1PBS thrice. The cover slips were mounted on slides using glycerol. The slides were observed under fluorescent microscope (Leica DM4000 B, Germany) under 20X magnification. 3. Results and discussion 3.1. Synthesis and formulation The thioether containing tridentate O, N, S donor ligand, 4-chloro-2-((2-(ethylthio)phenyl) diazenyl)phenol (L-SCH CH ) was synthesized as air stable red solid by diazo-coupling of 2- 2 3 (ethylthio)benzenamine with 4-chlorophenol following the reported method [26]. Stoichhiometric reaction between L-SCH CH and Rh(PPh ) (CO)Cl in acetonitrile under 2 3 3 2 refluxing condition yielded deep blue product (scheme 1). The complex was thoroughly characterized by several spectroscopic techniques. 1H NMR spectrum of the complex was taken Journal Pre-proof CDCl . The significant observation in the spectrum of the complex is the disappearance of S– 3 CH CH resonances due to cleavage of C-S bond. The structure of the complex is 2 3 unambiguously determined by single crystal X-ray diffraction method. Interestingly, instead of cleavage of sp3(C)-S bond [40], the sp2(C)-S bond is cleaved followed by removal of SCH CH 2 3 group and a direct Rh-C(aryl) bond formation is taking place in the complex. Due to desulfurization the modified ligand is coordinated as tridentate fashion to rhodium centre through azo-N, phenolic-O and aryl-C atom. Cl S PPh 3 [Rh(PPh ) (CO)Cl] 3 2 O N N OH N Refluxinacetonitrile Rh N for12h Cl PPh 3 Cl [Rh(PPh ) (L)Cl](1) L-SCH CH 3 2 2 3 Scheme 1. Synthesis of [Rh(PPh ) (L)Cl] (1) by C-S bond cleavage of L-SCH CH 3 2 2 3 3.2. Crystal structure The geometry of the complex was ascertained by single crystal X-ray diffraction method. Single crystals were grown by slow diffusion of dichloromethane solution of the complex into hexane at rt. The X-ray crystallographic data collection and refinement parameters of 1 are given in Table 1. Selected bond lengths and bond angles are summarized in Table 2. ORTEP plot of the molecular structure with the atomic numbering scheme for 1 is shown in Fig. 1. The rhodium atom adopts a distorted octahedral geometry and is coordinated by two PPh groups in trans 3 Journal Pre-proof positions of the octahedron, the modified chelating ligand (L) coordinated through phenolic-O, azo-N and aryl-C atoms. The vacant position of the square plane is occupied by chlorine atom. The deviation of the rhodium coordination sphere from the ideal octahedron is because of the small bite angles of the five membered chelate rings (Rh1-C1-C6-N2-N1) (78.97(17)°) and (Rh1-N1-C7-C12-O1) (80.25(14)°). The Rh-P (Rh1-P1, 2.4085(13) and Rh1-P2, 2.4288(14) Å), Rh-Cl (Rh1-Cl1, 2.4108(13) Å) and Rh-C (Rh1-C1, 2.023(4) Å) bond distances are found as expected for similar rhodium phosphine complexes [25, 41-43]. The azo, N-N bond distance in the complex is found to be elongated (N1-N2, 1.304(5) Å) supporting dπ(RhIII)π*(N=N) back donation. 3.3. Absorption and emission spectra The UV-vis spectrum of the complex 1 in acetonitrile exhibits two closed by low energy bands at 627 nm ( = 6390 M-1cm-1) and 583 nm ( = 5637 M-1cm-1) along with a shoulder at 535 nm. In addition a high energy sharp band is observed at 291 nm ( = 25627 M-1cm-1) along with the shoulder at 346 nm and 388 nm. Upon excitation at 583 nm in acetonitrile the complex exhibits very strong emission spectrum with  at 682 nm (Fig. 2). The emission quantum yield () of max the complex is found to be 0.103. Lifetime data of the emission decay curve was deconvoluted with respect to the lamp profile. The observed emission decay fits with bi-exponential profile with χ2 = 1.106 (Fig. 3). We have used mean fluorescence lifetime ( = a  + a  , where a and f 1 2 2 1 a are relative amplitude of decay process) to study the excited state stability of the complex. The 2 emission lifetime of the complex is found to be 2.26 ns. 3.4. DFT and TDDFT calculation The full geometry of the complex 1 was optimized by DFT method in singlet ground state using the B3LYP correlation functional. The optimized bond parameters for complex 1 are given in Journal Pre-proof Table 2. The calculated bond distances and angles are well correlated with the X-ray crystal structure data. The contour plots of selected molecular orbitals are given in Fig. 4. Energy and % of composition is summarized in Table 3. HOMO of the complex is found to be 93% π(L) character and concentrated on phenolate moiety of the ligand along with very minor contribution of dπ(Rh) orbital. HOMO-1 and HOMO-2 have mixed dπ(Rh), π(L) and pπ(Cl) character. The low energy unoccupied molecular orbital (LUMO) has 93% π*(L) character with major contribution of π*(N=N) orbital. The significant contribution of dπ(Rh) along with π(PPh ) orbitals is found to 3 be in LUMO+1 and LUMO+2 of the complex. To interpret the electronic spectra, singlet-singlet vertical electronic excitations were calculated by TDDFT/CPCM method in acetonitrile. Strong HOMO to LUMO transition is found to be at 593 nm (f = 0.1683) having ILCT character. One low energy weak transition corresponding to HOMOLUMO+1 transition (LMCT/ILCT character) at 515 nm is observed (Table 4). The high energy transition of the complex at 326 nm (f = 0.3676) corresponding to the experimental band at 291 nm. 3.5. Electrochemistry The electrochemical behavior of the complex was investigated by cyclic voltammetry (CV) in presence of [n-Bu N][ClO ] in acetonitrile at scan rate 50 mVS-1. In the potential window 1.5 to - 4 4 1.5 V complex 1 exhibits one quasi-reversible oxidation couple with E of 0.74 V (∆E = 100 1/2 mV) along with one quasi-reversible reduction couple (E = -1.18 V, ∆E = 130 mV) positive 1/2 and negative to the reference electrode respectively (Ag/AgCl) (Fig. 5). The redox behavior of the complexes is interpreted by DFT study. HOMO of the complex has 93% π(L) character with major contribution of phenolate moiety of the ligand, so the oxidation of the complex is assigned Journal Pre-proof as oxidation of phenolate moiety to form phenoxyl radical [19,44]. LUMO of the complex has 93% ligand character with major contribution of π*(N=N) orbital. Therefore the reduction of the complex is assigned as the reduction of azo(N=N) bond to form azo anion radical (L/L−) as expected. 3.6. Catalytic transfer hydrogenation The transfer hydrogenation is an important and efficient reaction in organic synthesis. So far many rhodium(III) complexes were used as effective catalysts for transfer hydrogenation reactions [21,43], which encourage us to use our synthesized Rh(III) cyclometalated complex as catalyst for the transfer hydrogenation of ketones. Initially to optimize the reaction condition, catalytic efficiency of complex 1 for the conversion of acetophenone to 1-phenylethanol was tested in iPrOH with the variation of catalyst to substrate ratio (C:S), reaction time and different bases and the results are summarized in Table 5. The conversion was found to be effective in presence of strong base KOH in comparison to Na CO , CH COONa or KOtBu. Again, to understand the catalytic efficiency of the complex 1, 2 3 3 different catalyst:substrate (C:S) ratios were tested in the transfer hydrogenation of acetophenone in i-PrOH/KOH. It is found that the conversion is maximum in C:S ratio of 1:300. With the variation of C:S ratio to 1:400 to 1:1500, the reaction still proceeds but a sharp decrease in rate of conversion is observed for C:S ratio 1:600 to 1:1500. The conversion is excellent with appreciable turnover number (TON) when the C:S ratio is 1:500 and hence this C:S ratio is the best choice for catalytic transfer hydrogenation reactions for complex 1. Again, to understand the effect of the catalyst, the reactions were also carried out in absence of the Rh(III) complex but no significant catalytic conversions were observed. A series of ketones were screened in transfer hydrogenation reaction using the optimum condition, C:S ratio of 1:500 and KOH as base. The Journal Pre-proof results are summarized in Table 6. The maximum conversions were observed for 1-(4- chlorophenyl)ethanone (99%), acetophenone (98%), 1-(p-tolyl)ethanone (98%) and p- nitroacetophenone (98%). The conversions of other acetophenones were found to be in the range of 91-97%. The catalytic efficiency of the present rhodium(III) cyclometalated complex is found to be very competitive with the reported transfer hydrogenation catalysts [45-47]. 3.7. Cell bio-imaging A yellow coloured tetrazolium salt MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was used to quantify mammalian cell survivability and proliferation. Mitochondria of viable cells reduce it to a non-fluorescent insoluble formazan, purple colour dye. Thus the degree of viability of cells can be determined by measuring the absorbance of the purple coloured solution at 570 nm. MTT experiment establishes that the rhodium(III) complex has moderate toxicity on human breast cancer cell line MCF-7 (Fig. 6). The IC value of the complex on 50 MCF-7 cell line is found to be 18.53 M. The chosen dose was taken to be lower than the IC 50 value of the complex at 10 M concentration. Upon incubation of MCF-7 cells with the complex causes a striking red fluorescence in the intracellular region (Fig. 7). This observation clearly indicates that the present luminescent rhodium(III) complex may be used as biomarker for fluorescence imaging. Through bright field images, it is observed that the treated cells do not show any distinct or visible morphological changes indicating that the cells are viable in the used concentration of the complex. 4. Conclusion Herein, we have synthesized a new fluorescent Rh(III) cyclometalated complex, [Rh(PPh ) (L)Cl] (1) via C-S bond activation of a thioether containing azo-phenol ligand (L- 3 2 SCH CH ). The distorted octahedral geometry of the complex is confirmed by X-ray structure. 2 3 Journal Pre-proof The complex exhibits a quasi-reversible oxidation couple (E = 0.74 V, E = 100 V) along with 1/2 quasi-reversible reduction peak at E = -1.18 V (∆E = 130 mV). The complex exhibits low 1/2 energy emission band at 682 nm with high emission quantum yield ( = 0.103). Cytotoxicity of the complex is studied by MTT method with human breast cancer cell lines (MCF-7) and IC 50 value is found to be 18.5 M. In presence of the complex (10 M) a bright red fluorescence image of MCF-7 cell lines is observed under fluorescence microscope. The complex exhibits efficient catalytic activity towards transfer hydrogenation of ketones. Acknowledgment Financial supports received from the Science and Engineering Research Board (SERB), New Delhi, India (EEQ/2018/000266) is gratefully acknowledged. P. Roy and R. Naskar are thankful to UGC, New Delhi, India for fellowship. C. K. Manna is grateful to RUSA 2.0 programme for fellowship. Supplementary materials Crystallographic data for the structure of 1 has been deposited with the Cambridge Crystallographic Data center, CCDC No. 1496012. Copies of this information may be obtained free of charge from the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (e-mail: deposit@ccdc.cam.ac.uk or www:htpp://www.ccdc.cam.ac.uk). Reference [1] W.L. Su, Y.C. Yu, M.C. Tseng, S.P. Wang, W.L. Huang, Dalton Trans. (2007) 3440-3449. [2] L.S. Forster, J.V. Rund, Inorg. 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Crystallographic data for [Rh(Cl)(PPh ) (L)] (1) 3 2 Formula C H Cl N OP Rh 48 37 2 2 2 Formula Weight 893.55 Crystal System Monoclinic Space group P2 /c 1 a, b, c [Å] 12.6327(5), 19.1782(7), 18.7752(6) β 109.558(2) V [ Å3] 4286.3(3) Z 4 D(calc) [g/cm3] 1.385 Mu(MoKa) [ /mm] 0.636 F(000) 1824 Crystal Size [mm] Temperature (K) 293(2) Radiation [Å] 0.71073 θ(Min-Max) [°] 2.01- 27.25 Dataset (h; k; l) -15 and 15; -24 and 23; -24 and 24 Total, Unique Data, R(int) 66181, 9459, 0.0880 Observed data [I > 2σ(I)] 5716 Nref, Npar 9459, 506 R1, wR2[I >2(I)] 0.0666; 0.1576 GOF 1.031 Largest diff. Peak/hole, (e Å─3) -1.290; 1.617 Journal Pre-proof Table 2. Some selected bond distances (Å) and angles (°) of [Rh(Cl)(PPh ) (L)] (1) 3 2 Bonds(Å) X-ray Calc. Rh1-N1 1.972(3) 2.006 Rh1-C1 2.023(4) 2.016 Rh1-O1 2.220(3) 2.278 Rh1-P1 2.4085(13) 2.457 Rh1-P2 2.4288(14) 2.457 Rh1-Cl1 2.4108(13) 2.445 N1-N2 1.304(5) 1.277 O1-C12 1.327(6) 1.298 N1-C7 1.416(6) 1.391 C1-C6 1.423(6) 1.429 Angles(o ) N1-Rh1-C1 78.97(17) 79.252 N1-Rh1-O1 80.25(14) 78.009 C1-Rh1-O1 159.19(16) 157.262 N1-Rh1-P1 90.36(11) 93.349 C1-Rh1-P1 91.27(14) 92.094 O1-Rh1-P1 89.98(10) 89.231 N1-Rh1-P2 95.60(11) 93.350 C1-Rh1-P2 91.40(14) 92.094 O1-Rh1-P2 89.50(10) 89.233 O1-Rh1-Cl1 100.83(10) 102.099 N1-Rh1-Cl1 178.62(11) 179.890 C1-Rh1-Cl1 99.97(14) 100.638 Journal Pre-proof Table 3. Energy and compositions of some selected molecular orbitals of 1 MO Energy % Composition Rh PPh L Cl 3 LUMO+5 -0.55 01 95 03 0 LUMO+4 -0.60 01 98 0 01 LUMO+3 -0.61 01 94 05 0 LUMO+2 -0.84 29 47 20 04 LUMO+1 -1.70 33 54 08 05 LUMO -2.27 04 03 93 0 HOMO -4.98 05 02 93 0 HOMO-1 -5.78 35 03 27 36 HOMO-2 -5.91 11 34 26 29 HOMO-3 -6.20 14 12 53 21 HOMO-4 -6.26 09 40 51 0 HOMO-5 -6.36 06 38 42 14 HOMO-6 -6.62 02 76 12 09 HOMO-7 -6.69 01 97 02 01 HOMO-8 -6.70 02 92 03 03 HOMO-9 -6.84 02 82 12 04 HOMO-10 -6.86 10 78 10 02 Journal Pre-proof Table 4. The experimental absorption bands and the electronic transitions calculated with the TDDFT/B3LYP/CPCM method for complex 1  Osc.  (nm) expt. (nm) E (eV) Strength (f) Key excitations Character (ε (M-1cm-1)) 593.3 2.0896 0.1683 (97%)HOMOLUMO ILCT 627 (6390) 515.2 2.4064 0.0108 (93%)HOMOLUMO+1 LMCT/ILCT 583 (5637) 414.1 2.9939 0.0104 (96%)HOMO-1LUMO MLCT 535 (sh) 375.4 3.3028 0.0366 (67%)HOMO-3LUMO ILCT 388 (sh) 365.0 3.3971 0.0641 (82%)HOMO-4LUMO ILCT 352.5 3.5175 0.0625 (62%)HOMO-2LUMO+3 ILCT 346 (sh) 337.8 3.6702 0.1418 (69%)HOMO-3LUMO+3 ILCT 326.2 3.8009 0.3676 (72%)HOMO-5LUMO ILCT 291 (25627) Journal Pre-proof Table 5. Effect of C:S ratio, base and reaction time on the transfer hydrogenation of acetophenonea O OH Complex1 i-PrOH,Base Entry C:S ratio Base Time (h) Conversionb (%) TONc 1 1:300 KOH 3 67 202 2 1:300 KOH 4 81 244 3 1:300 KOH 5 99 296 4 1:300 KOH 7 99 297 5 1:300 KOH 10 99 297 6 1:300 NaOH 5 96 287 7 1:300 Na CO 5 53 158 2 3 8 1:300 CH COONa 5 43 128 3 9 1:300 KOtBu 5 67 200 10 1:400 KOH 5 98 392 11 1:500 KOH 5 98 488 12 1:600 KOH 5 84 506 13 1:800 KOH 5 69 548 14 1:1000 KOH 5 43 428 15 1:1500 KOH 5 25 398 aReaction condition: acetophenone (3 mmol), complex 1 (10-2 mol), catalyst:KOH 1:4 in i- PrOH (10 mL) at 80 ºC; bConversions were determined by GC with undecane as an internal standard and were reported mean values of three runs; cTurnover number (TON) = mole of product/mol of catalyst. Journal Pre-proof Table 6. Transfer hydrogenation of ketones using complex 1a Complex1 O OH C:S=1:500 OH O + + R1 R2 KOH,Refluxfor5h R1 R2 Entry Ketones Alcohols Conversion TONc (%)b 1 O OH 98 488 2 O OH 94 472 3 O OH 95 476 4 O OH 96 479 5 O OH 94 468 6 O OH 92 458 7 O OH 98 491 8 O OH 99 493 Cl Cl 9 O OH 97 493 Br Br 10 O OH 98 492 O2N O2N aExperimental condition: reactions were carried out at 80 °C, ketone (3 mmol), Rh(III) complex (0.2 mol%), KOH (0.1 mmol), i-PrOH (10 mL); bConversions were determined by GC with undecane as an internal standard and were reported mean values of three runs; cTurnover number (TON) = mole of product/mol of catalyst Journal Pre-proof Figure captions Fig. 1. ORTEP plot with 35% ellipsoidal probability of 1 Fig. 2. UV-vis () and emission () spectra of complex 1 in acetonitrile Fig. 3. Life time decay profile of 1 () ( = 490 nm) and prompt (■■■) in acetonitrile ex Fig. 4. Contour plots of selected molecular orbitals of 1 Fig. 5. Cyclic voltammogram of 1 in acetonitrile with respect to Ag/AgCl reference electrode ([n-Bu N][ClO ] was used as the supporting electrolyte) 4 4 Fig. 6. MTT assay of complex 1 on MCF-7 cell line Fig. 7. (a) Fluorescence image, (b) bright field image and (c) merged image of human breast cancer cell lines (MCF-7) in presence of complex 1 Fig. 1 35 30 25 20 15 10 5 0 300 400 500 600 700 800 900 Fig. 2 1-   ) mc     ).u.a( ytisnetnI noissimE Journal Pre-proof  nm Journal Pre-proof Fig. 3 HOMO HOMO-1 HOMO-2 LUMO LUMO+1 LUMO+2 Fig. 4 Fig. 5 120 100 80 60 40 20 0 nt r ol 5 1 0 1 5 2 0 3 0 5 0 7 5 1 0 0 o c Conc. in M ytilibavivruS % Journal Pre-proof Fig. 6 Journal Pre-proof a b c Fig. 7 Journal Pre-proof There are no conflicts of interest to declare.