Potent Photochemotherapeutic Activity of Iron(III) Complexes on Visible Light-induced Ligand to Metal Charge Transfer

Article abstract of DOI:10.1246/cl.200139

Five new ternary iron(III) complexes with phenolate-based ligands of general molecular formula, [Fe(L¹)B] and [Fe(L²)B], where L¹ = 2-(bis(2-hydroxybenzyl)amino)acetic acid, L² = 2-bis[3,5-di(tert-butyl)-2-hydroxybenzyl]aminoacetic acid, B = phen (1,10-phenanthroline), ip (1H-imidazo[4,5-f ][1,10]phen-anthroline) and pyip (2-(pyren-1-yl)-1H-imidazo[4,5-f ][1,10]-phenanthroline) were synthesized and probed for visible light-induced cytotoxicity in human cervical carcinoma (HeLa) cells. The complexes in generating hydroxyl radicals from molecular oxygen on visible light-induced phenolate(O)?Fe(III) or carboxylate(O)?Fe(III) charge transfer prompted apoptosis in HeLa cells with IC₅₀ values in the range of 4.624.3 ˉM while remaining non-toxic in dark.

Full text of DOI:10.1246/cl.200139

Advance Publication Cover Page
Potent photochemotherapeutic activity of iron(III) complexes on visible light-induced ligand
to metal charge transfer
S. Binita Chanu, Md Kausar Raza, Dulal Musib, Mrityunjoy Pal, Maynak Pal, and Mithun Roy*
Advance Publication on the web April 3, 2020
doi:10.1246/cl.200139
© 2020 The Chemical Society of Japan
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1
Potent photochemotherapeutic activity of iron(III) complexes on visible light-induced ligand to
metal charge transfer
S. Binita Chanu1, Md Kausar Raza2, Dulal Musib1, Mrityunjoy Pal1, Maynak Pal1 and Mithun Roy1*
1Department of Chemistry, National Institute of Technology, Manipur, Langol 795004, Imphal (Manipur), India;
2Department of Inorganic and Physical Chemistry, Indian Institute of Science Bangalore, Bangalore-560012, Karnataka, India
E-mail: mithunroy@nitmanipur.ac.in, mithunroy_nitmn@yahoo.com
1
2
3
4
5
6
7
8
9
Five new ternary iron(III) complexes with phenolate-based
ligands of general molecular formula, [Fe(L1)B] and
[Fe(L2)B], where L1 = 2-(bis(2-hydroxybenzyl)amino)acetic
acid, L2 = 2-bis-[3,5-di(tert-butyl)-2-hydroxybenzyl]amino
acetic acid, B = phen, (1,10-phenanthroline), ip, (1H-
imidazo[4,5-f][1,10]phenanthroline) and pyip, (2-(pyren-1-
49 only chelate metal ions, but also provide us with a platform
50 to covalent anchoring of wide range of chromophores.19-22
51
The 1,10-phenanthroline ligand in complexes 2 and 5
52 was incorporated with pyrene group that own fascinating
53 photophysical behaviors. 1,10-phenanthroline scaffold is
54 found to be medicinally active. Moreover, induced photo-
55 chemistry of imidazo-1,10-phenanthroline in complexed
56 form23-27 has prompted us to synthesize five new ternary
57 iron(III) complexes of the general molecular formula
58 [Fe(L1)B] (1-2) and [Fe(L2)B] (3-5), where L1 = 2-(bis(2-
59 hydroxybenzyl)amino)acetic acid, L2 = 2-bis-[3,5-di(tert-
60 butyl)-2-hydroxybenzyl]amino acetic acid, B = phen,(1,10-
yl)-1H-imidazo[4,5-f][1,10]phenanthroline)
were
synthesized and probed for visible light-induced
cytotoxicity in human cervical carcinoma (HeLa) cells. The
10 complexes in generating hydroxyl radicals from molecular
11 oxygen on visible light-induced phenolate(O)→Fe(III) or
12 carboxylate(O)→Fe(III) charge transfer prompted apoptosis
13 in HeLa cells with IC50 values in 4.6-24.3 µM while non-
14 toxic in dark.
61 phenanthroline),
62 f][1,10]phenanthroline) and pyip, (2-(pyren-1-yl)-1H-
63 imidazo[4,5-f][1,10]phenanthroline)and chemically
ip,
(1H-imidazo[4,5-
15
16 Keywords:
17 Photocytotoxicity in HeLa cells · Apoptosis
Ternary
iron(III)
complexes
·
64 evaluated the visible light-induced anticancer activity in
65 HeLa cells (Scheme 1).
18
Electronic transitions (e.g. metal to metal charge transfer
19 or d-d transition, ligand to metal or metal to ligand charge
20 transfer, intra-ligand charge transfer, inter-valence charge
21 transfer) in transition metal complexes often resulted in
22 ligand exchange or displacement, isomerization, redox
23 reactions.1-2 This provide an excellent platform to use
24 coordination
compounds
as
the
potential
25 photochemotherapeutic agents in lieu of porphyrin-based
26 photodynamic therapy (PDT) drugs.3-5 Although later
27 transition metal-based compound exhibiting photo-
28 chemotherapeutic activity in lower energy light (>600 nm)
29 are relatively less, there are plenty of first row transition
30 metal-based compounds showing remarkable PDT effect in
31 lower energy light (>600 nm) which is considered to be the
32 essential requirement for photochemotherapy.6 Iron(III)
33 being a Lewis acid in character are best stabilized by the π-
34 donor ligands like carboxylate-O or phenolate-O in which
35 there was a reduced energy gap between t2g and eg* in an
36 octahedral complex.7 This resulted in low energy metal
37 centered or LMCT transition.8,9 Photo-activation on LMCT
38 band of such complexes lead to homolytic cleavage of metal
39 to ligand bond resulting in oxidation of the ligand
40 (carboxylate-O or phenolate-O) and reduction of iron(III)
41 into iron(II).10-12 This intramolecular photo-redox reaction
42 lead to the generation of extremely toxic reactive oxygen
66 Scheme 1. Schematic representation of ternary iron(III) complexes.
67
68
The five new ternary iron(III) complexes(1-5), have been
69 synthesized in good yield (50-58%) by mixing
70 Fe(NO3).9H2O have been synthesized in good yield (50-
71 58%) by mixing Fe(NO3).9H2O into the solution of 2-(bis(2-
72 hydroxybenzyl)amino)acetic acid (L1) or 2-bis-[3,5-di(tert-
73 butyl)-2-hydroxybenzyl]amino acetic acid (L2) in a mixture
74 of MeOH, EtOH and MeCN (3:3:2 v/v) containing
75 triethylamine followed by the addition of imidazo-1,10-
76 phenanthroline base with constant stirring at room
77 temperature. Addition of diethylether into the mixture and
78 subsequent drying yielded the microcrystalline complexes
79 (1-5) in analytically pure form (Scheme S1). Elemental
80 analysis revealed about the purity of the complexes and
81 further the complexes were characterized spectroscopically
82 and analytically (Table S1, Figure S1-S6). Lower value of
83 molar conductance (15-22 Sm2M−1) in aqueous DMSO
84 (10% v/vDMSO-H2O) suggested neutral complexes
85 correlating with the proposed structure of the complexes
86 (Scheme 1).17 All the complexes were found to exhibit the
87 stretching frequency characteristic of double bond stretching
•-
43 species (ROS) like superoxide anions (O2 ), hydroxyl
44 radicals.13-14 Therefore, ability of the iron(III) complexes
45 with phenolate or carboxylate-based ligands generating
46 ROS on activation with low energy light have shown
47 potential for photochemotherapeutic applications.15-18 On the
48 other hand, imidazo-1,10-phenanthroline as a ligand not

2
1
2
3
4
5
6
7
8
9
mode of C=N group at ∼1630 cm−1 in addition to
carboxylate C=O asymmetric stretching IR band ranging
from 1490-1530 cm-1 in the IR spectra of the complexes
(Figure S1). Protonated molecular ions [MH]+ were
detected in the Q-TOF ESI mass spectra of the complexes.
Isotopic distribution correlated with the proposed molecular
formula and structure of the complexes (Table S1, Figure
S2-S6). Based on the proposed structure, we carried out
DFT calculations to obtain energy minimized structure and
48
The complexes exhibited quasi-reversible cyclic-
49 voltametric (cathodic) responses (Fe3+/Fe2+) with E½ at ~ -
50 1.5 V versus Ag/AgCl as reference electrode in DMF–0.1ꢀM
51 Tetrabutylammoniumperchlorate (TBAP) (Figure 1, Table
52 S2, Figure S11-S15). High negative value of E½ indicated
53 increased stability of the Fe(III) state of the complexes.
54 Reduction of pyrenyl moieties of the complexes 2 and 5
55 were observed at -1.5 V.24 Remarkably high stability of the
56 Fe(III) state render the complexes to be unaffected by the
57 cellular thiols and thereby reducing the scope of dark
58 toxicity.
10 corresponding HOMO/LUMO stereographs were shown in
11 Figure S7. The UV-Visible spectra of the complexes (1-5)
12 were recorded in DMSO:H2O (10% /vDMSO/H2O). The
v
59
Photochemical hydroxylation of benzoic acid into
60 salicylic acid was assess to determine the photo-activated
61 generation of hydroxyl radical (•OH) using UV-Visible
62 spectroscopy (Figure S16).25-27 The complex 5when
63 photoactivated at LMCT band generated hydroxyl radicals
64 which converted benzoic acid into salicylic acid forming
65 Fe(III)-salicylate complex on external addition of a
66 methanolic solution of Fe(NO3)3·9H2O. The resulting
67 Fe(III)-salicylate complex absorb at 520 nm in the UV-
68 visible spectra. Herein, although the LMCT bands of the
69 complex was centered on ~520 nm, we observed appearance
70 of new LMCT bands at 580 nm on visible light (400-700 nm,
71 10 J cm-2) irradiation followed by external addition of Fe3+.
72 This result was stimulating as we might predict the
13 phenolate (O)(pπ)→Fe(III)(dπ*) LMCT transitions was
14 observed with ꢀmax 410 nm for complex 3 and the other four
15 complexes in the range 500-610 nm. The presence of
16 imidazo group in the complexes 1, 2, 4 and 5 has
17 remarkably red-shifted the LMCT transition or electron
18 donating pyrenyl group reduced the energy differences in
19 HOMO-LUMO for LMCT transition.22-23
20
•
73 formation of excess amount of OH radical leading to the
74 formation of catechol or more specifically 2,3-dihydroxy-
75 benzoic acid from benzoic acid which readily chelate
76 externally added Fe3+ resulting in the formation of Fe (III)-
77 catecholate having typical LMCT band at λmax>550 nm.26-27
78 FT-IR experiment of the complex 5 upon exposure to visible
79 light (400-700 nm, 10 J cm-2) in regular time interval have
80 shown the process of decarboxylation and liberation of CO2
81 indicating the homolytic cleavage of Fe-O(carboxylate)
82 bond which led to the photodecarboxylation (Figure S17).11
21 Figure 1. The UV-visible spectrum of the complexes 1-5 in 10% v/v
22 DMSO-H2O at 250C. The inset shows cyclic voltammogram of
23 complex
4 in 1 mM in DMF in presence of 0.1 M TBAP
24 (Tetrabutylammonium perchlorate) as supporting electrolyte. Ag/AgCl
83
Intra-cellular uptake of the complexes was studied by
25 reference electrode was used here.
26
84 FACS analysis. Blue fluorescence of the complexes was
85 explored to study the uptake in HeLa cells. Enhanced
86 fluorescence of treated HeLa cells comparing the control
87 HeLa cells indicated significant uptake of the complexesthe
88 complexes (1-5) in HeLa cells (Figure S18, Figure S19).
27
Other ligand centered electronic transitions like ꢁꢁ* or
28 nꢁ* were observed at <400 nm (Figure 1). Stability of the
v
29 complexes in DMSO:H2O (10%
/
v
DMSO-H2O) was
30 studied from UV-visible spectral measurements in a time
31 dependent manner till 12 hours (Figure S8). There was no
32 change in UV-visible spectra of the complexes indicating
33 inertness of the complexes making them suitable for
34 biological applications. However, UV-A light was
35 responsible for partial changes in UV-visible spectra of the
36 complexes.
89
The MTT assay was performed to investigate the
90 cytotoxic properties of the ligands and iron(III) complexes
91 (1-5) in dark and in visible light (400-700 nm, 10 Jcm-2).17,
92 28-32 The ligand pyip being insoluble in biological medium
93 IC50 value was not determined. Approximately 1.5 x
94 104number of HeLa cells was treated with the complexes in
95 a dose-dependent manner followed byphoto-irradiation with
96 visible light (400–700 nm, 10 Jcm−2, Luzchem photoreactor)
97 for one hour. Proper dark control was maintained under the
98 similar experimental condition except photo-irradiation to
99 determine the cytotoxicity of the complexes in dark. The
100 complexes exhibited remarkable influence on the anticancer
101 activities of the complexes, and their half maximal
102 inhibitory concentrations (IC50) were determined from non-
103 regression analysis of the cell viability plot against dose in
104 micromolar (Figure S20, Table 1). The treatment of HeLa
105 cells with the iron(III) complexes (1-100 μM) resulted in a
106 significant decrease in cell viability when photo-irradiated
37
The emission spectra of the pyrenyl ligand was recorded
38 in DMSO along with complexes (1-5) in (10%v/vDMSO-
39 H2O) at room temperature (Figure S9). Although the ligand
40 was highly emissive in 452 nm, paramagnetic nature of the
41 complexes exhibited very low intensity luminescence in
42 420-460 nm under the same experimental condition. The
43 photostability of the pyrenyl ligand was recorded using
44 luminescence spectroscopy in different time-interval by
45 illuminating visible light (400-700 nm, 10 Jcm-2) upto 48hrs
46 (Figure S10). No change in fluorescence spectra of the
47 pyrenyl ligand indicated its photostability.

3
23 Figure 2. Fluorescence Assisted Cell Sorting (FACS) analysis for ROS
24 generation by complexes (2 and 5) using DCFDA dye. Generation of
25 ROS is highlighted by the shift in fluorescence band positions
26 compared to cells alone in HeLa cells treated with complexes 2 and 5,
27 under different experimental conditions as shown by the colour codes
1
2
3
and the IC50 values were determined in the ranges 4.6-24.3
μM. Complexes were non-toxic to HeLa cells with IC50>100
μM in dark. Photocytotoxicity of the complex 5 with t-Bu
4 group attached facilitated the LMCT transition on photo-
5 activation and thereby stabilizing the phenol radicals.
6 The other N,N donor ligands could stabilize the resultant
7 Fe(II) due to its strong ꢁ-acid character facilitating the
8 photo-decarboxylation or phenolate(O)-Fe(III) charge
9 transfer. This prompted and facilitated the photo-fenton
10 chemistry in generating cytotoxic hydroxyl radicals. This
11 explains higher cytotoxicity of the complex 5.
12 The photocytotoxicity index (PI) were found to be
13 remarkably high (>25) for the complex 5 with other
14 complexes the value was at least >4. Reference to the IC50
15 value (4.3 μM) of photofrin® against HeLa cells on red-light
16 exposure and 43.0 μM in dark with photocytotoxicity index
17 (PI) ~10, the complex 5 has emerged as viable alternative of
18 present PDT drugs in our present studies.33 Similar iron(III)
28
29
30
The ability of the complexes in generation hydroxyl
31 radicals as the reactive oxygen species (ROS)on photo-
32 activation at LMCT band of the complexes, prompted up to
33 study the photo-activated generation of ROS in vitro. The
34 2′,7′-dichlorofluorescein diacetate (DCFH-DA) assay was
35 performed in which intracellular esterase hydrolyse DCFH-
36 DA into 2′,7′-dichlorofluorescein (DCF) and further
37 oxidized by intracellular ROS into oxidized form of 2′,7′-
38 dichlorofluorescein (DCF) emitting green light. This was
39 determined by fluorescence assisted cell sorting (FACS)
40 method.34-35 Increased concentration of ROS in HeLa cells
41 would result in greater shift in fluorescence intensity. We
42 observed enhanced green fluorescence when HeLa cells
43 were treated with the complexes 2 and 5 even in dark
44 indicating generation of ROS by the complexes. However,
45 irradiation of visible light on the treated HeLa cells
46 remarkably increased the generation of ROS (Hydroxyl
19 complexes
previously
exhibited
remarkable
20 photocytotoxicity on photoexcitation at broad phenolate
21 (O)→Fe(III) or carboxylate(O)→Fe(III) bands in the range
22 400-700 nm.26
47 radicals).
This
has
accounted
for
remarkable
Table 1. Photocytotoxicity of the ternary iron(III)
complexes (1-5).
48 photocytotoxicity of the complexes in HeLa cells (Figure 2).
49
Complexes
HeLa cells
50
IC50 / ꢂM
51
Darka
Lightb
52
1
2
3
4
>100
>100
>100
>100
>100
>100
ND
>100
24.0
>41.0
24.3 (±4.3)
18.5 (±1.2)
11.1 (±1.0)
8.2 (±1.8)
4.6 (ꢃ0.4)
58.2 (±0.2)
ND
53
54
55
56
57
5
58
ipc
59
pyipc
60
Fe(NO3)3.9H2Od
Cisplatine
>100
61
62
63 Figure 3. Confocal images of HeLa cells treated with the complex 5
64 and stained with acridine orange (AO) and ethidium bromide (EB)
65 recorded in green (540-600 nm) and red channels (710-780 nm) without
66 (control).
-
e
Photofrin®
4.3 (±0.2)
IC50 values correspond to 24 h incubation in dark. bIC50 values
a
correspond to 4 h incubation in the dark followed by photoexposure to
visible light (400-700 nm,10 J cm-2). cIC50 values of ip and pyip
67
68
d
adapted from the reference 17. IC50 values of Fe(NO3)3.9H2O adapted
Changes of chromatin reorganization upon photo
e
from the reference 22. The IC50 value of cisplatin and photofrin® was
69 irradiation of complex 5 in HeLa cells was determined by
70 acridine orange and ethidium bromide (AO/EB) dual
71 staining. Segregation of the live cells and dead cells are
72 based on membrane integrity. AO stains live cell’s DNA
73 generating green fluorescence, contrasting EB, which is
74 excluded from live cells, bearing intact plasma
75 membrane and stains the DNA of dead cells, generating
76 orange fluorescence. HeLa cells are treated with 5
77 (10 µM) for 4 hour and kept in dark, displaying green
78 fluorescence analogues to emission of AO, although
79 upon photo irradiation, the intensity of red emission
80 increased significantly, indicating photo-induced cell
81 death (Figure 3).36-37 It was understood that there was
82 apoptosis in HeLa cells resulted from generation of excess
83 of hydroxyl radicals from the photo-activated iron(III)
84 complexes. Excitation of the complexes with visible light
adapted from reference 18. ND: Not Determine

4
62 13. A. Garai, Armin Gandhi, V. Ramu, M. K. Raza, P. Kondaiah, A.
1
2
3
4
5
6
7
8
9
led to phenolate (O)→Fe(III) or Carboxylate (O)→Fe(III)
charge transfer resulting in homolytic cleavage of Fe-O
bonds and iron(III) was reduced to active iron(II). Iron(II)
center generated on photo-activation, produced hydroxyl
radicals along with superoxide anions or peroxide from
molecular oxygen (Scheme S2).38-39 This was the leading
cause of oxidative stress in HeLa cells and subsequent
apoptosis.
63
R. Chakravarty,ACS Omega 2018, 3, 9333.
64 14. U. Basu,Imran Khan, A. Hussain, B. Gole, P. Kondaiah, A. R.
65
Chakravarty, Inorg. Chem. 2014, 53, 2152.
66 15. L. Xie, Z. Luo, Z. Zhao, T. Chen,J. Med. Chem. 2017, 60, 202.
67 16. U. Basu, I. Khan, A. Hussain, P. Kondaiah, A. R Chakravarty,
68
Angew. Chem. Int. Ed. Engl. 2012, 51, 2658.
69 17. (a) D. Musib, M. K. Raza, S. Kundu, M. Roy, Eur. J .Inorg.
70
71
72
Chem. 2018, 2018, 2011. (b) S. Paul, P. Kundu, U. Bhattacharyya,
A. Garai, R. C. Maji, P. Kondaiah, A. R. Chakravarty, Inorg.
Chem. 2020, 59, 913.l9
Commitment towards the fulfillment of required
10 photoactive anticancer activities prompted us to synthesize
11 five new ternary iron(III) complexes. Exciting the
12 complexes with visible light (400-700 nm, 10 Jcm-2)
73 18. (a) D. Musib, S. Banerjee, A. Garai , U. Soraisam, M. Roy,
74
75
Chemistry Select 2018, 3, 2767. (b) C. Imberti, P. Zhang, H.
Huang, P. J. Sadler, Angew. Chem. Int. Ed. Engl. 2020, 59, 61.
76 19. M. Stephenson, C. Reichardt, M. Pinto, M. Wächtler, T.
13 resulted
in
phenolate(O)→Fe(III)
or
77
78
Sainuddin, G. Shi, H. Yin, S. Monro, E. Sampson, B. Dietzek, S.
A. McFarland, J. Phys. Chem. A 2014,118,10507.
14 carboxylate(O)→Fe(III) charge transfer and subsequent
15 photo-redox chemistry was responsible for the generation of
16 excess of hydroxyl radicals in HeLa cells. This induced
17 oxidative stress followed by apoptosis in HeLa cells that
18 explain remarkable photo-cytotoxicity of the iron(III)
19 complexes. The present initiative on exploring the chemistry
20 of iron(III) for photo-activated anticancer activity could be
21 promising towards designing next generation photo-
22 chemotherapeutic agents.
79 20. Z. Liu, J. Zhang, Y. Sun, C. Zhu, Y. Lu, J. Wu, J. Li, H. Liu, and Y.
80
Ye, J. Mater. Chem. B 2020, 8, 438.
81 21. A. Hussain, M. F. AlAjmi, Md. T. Rehman, S. Amir, F. M.
82
83
Husain, A. Alsalme, M. A. Siddiqui, A. A. AlKhedhairy & R. A.
Khan, Sci. Rep. 2019, 9, 5237.
84 22. T. K. Goswami, S. Gadadhar, M. Roy, M. Nethaji, A. A. Karande,
85 A. R. Chakravarty, Organometallics 2012, 31, 3010.
86 23. N. Mukherjee, S. Podder, S. Banerjee, S. Majumdar, D. Nandi, A.
R.Chakravarty, Eur. J. Med. Chem. 2016, 122, 497.
87
88 24. (a)T. K. Goswami, S. Gadadhar, B. Balaji, B. Gole, A. A. Karande
23
89
90
and A. R. Chakravarty, Dalton Trans. 2014, 43, 11988. (b) M. A.
Rizvi, R. M. Syed and B. Khan, J. Chem. Educ. 2011, 88(2), 220-222.
91 25. S. Gazi and R. Ananthakrishnan, Curr. Anal. Chem. 2012, 8, 143.
24
M.R. gratefully thanks the Board of Research in Nuclear
25 Science (BRNS), Mumbai (37(2)/14/18/2017-BRNS)
26 financial support. The authors thank the National Institute of
27 Technology, Manipur for providing research facilities.
28 S.B.C. greatly acknowledges funding support through
29 Department of Science and Technology (DST) (Women
30 Scientist A Scheme (SR/WOSA/CS-31/2016)), Government
31 of India. We Prof. Akhil R. Chakravarty for his help in
32 conducting cytotoxicity studies at IISc Bangalore.
33
92 26. S. B. Chanu, M. K. Raza, S. Banerjee, P. R. Mina, D. Musib, M.
93
Roy, J. Chem. Sci. 2019, 131, 9.
94 27. T.Sarkar, S. Banerjeeand Akhtar Hussain, RSC Adv.2015, 5, 29276.
95 28. S. Saha, R. Majumdar, M. Roy, R. R. Dighe, A. R. Chakravarty,
96
Inorg. Chem. 2009, 48, 2652.
97 29. A. V. Singh, V. Vyas, E. Maontani, D. Cartelli, D. Parazzoli,A.
98
99
Oldani,G. Zeri,E. Orioli,D. Gemmati, and P. Zamboni, J Neurosci
Rural Pract. 2012, 3, 301.
100 30. M. Kongot, D. S. Reddy, V. Singh, R. Patel, N. K. Singhal and A.
101
Kumar, New J. Chem. 2019, 43, 10932.
102 31. V. F. S. Pape, N. V. May, G. T. Gál, I. Szatmári, F. Szeri, F.
Fülöp, G. Szakács and É. A. Enyedy, Dalton Trans. 2018, 47, 17032.
104 32. S. Roy, S. Roy, S. Saha, R. Majumdar, R. R. Dighe, E. D. Jemmis
and A. R. Chakravarty, Dalton Trans. 2011, 40, 1233.
106 33. K. Mitra , S. Gautam , P. Kondaiah and A. R. Chakravarty , Angew.
Chem., Int. Ed. 2015, 54, 13989.
108 34. T. Sarkar , R. J. Butcher , S. Banerjee , S. Mukherjee and A.
Hussain , Inorg. Chim. Acta. 2016, 439, 8.
110 35. M. K. Raza , S. Gautam , A. Garai , K. Mitra , P. Kondaiah and A. R.
Chakravarty , Inorg. Chem. 2017, 56, 11019 .
112 36. B. Marydasan, R. R. Nair, P. S. S. Babu, D. Ramaiah, and S. A.
Nair, ACS Omega 2019, 4, 12808.
34 Supporting
35 http://dx.doi.org/10.1246/cl.******.
Information
is
available
on
103
105
107
109
111
113
36 References
37 1. N. A. Smith and P. J. Sadler, Phil. Trans. R. Soc. A 2013, 371,
20120519.
39 2. A. W. Adamson, W. L. Waltz, E. Zinato, D. W. Watts, P. D.
Fleischauer, R. D. Lindholm, Chem. Rev. 1968, 68, 5, 541.
38
40
41 3. I. Yoon, J. Zhu Li, and Y. K. Shim, Clin Endosc. 2013, 46, 7.
42 4. K. J. Franz, N. Metzler-Nolte, Chem. Rev. 2019, 119, 727.
43 5. L. K. McKenzie,H. E. Bryant,J. A. Weinstein, Coord. Chem. Rev.
44
2019, 379, 2.
45 6. A. R. Chakravarty, M. Roy, Prog. Inorg. Chem., 2012, 57(1), 119.
114 37. J. Chen, W. R.Browne, Coord. Chem. Rev. 2018, 374, 15.
46 7.
(a) X. Li, S. Lee, Yoon, J. Chem. Soc. Rev. 2018, 47, 1174.(b)S.
Monro, K. L. Colón, H. Yin, J. Roque III, P. Konda, S. Gujar, R.
P. Thummel, L. Lilge, C. G. Cameron, S. A. McFarland, Chem.
Rev. 2019, 119, 797.
115 38. N. Lehnert, F. Neese, R. Y. N. Ho, L. Que, Jr. and E. I. Solomon,
116
J. Am. Chem. Soc. 2002, 124, 10810.
47
117 39. S. Sahuand D. P. Goldberg, J. Am. Chem. Soc. 2016, 138, 11410.
48
49
50 8. F. A. Cotton, G. Wilkinson, C. A. Murillo and M. Bochmann,
51
52
Advanced Inorganic Chemistry, 6th Edition, Willey, New York,
1999.
53 9. F. Li, K. K Meier, M. A Cranswick, M. Chakrabarti, K. M Van
54
55
Heuvelen, E. Munck, L. Que Jr, J. Am. Chem. Soc. 2011, 133,
7256.
56 10. M. Roy, T. Bhowmick, R. Santhanagopal, S. Ramakumar, A. R.
57
Chakravarty, Dalton Trans. 2009, 24, 4671.
58 11. M. Roy, T. Bhowmick, S. Ramakumar, M. Nethaji, A. R.
Chakravarty, Dalton Trans. 2008, 27, 3542.
60 12. (a) S. B. Chanu, S. Banerjee, M. Roy, Eur. J. Med. Chem.
2017,125,816.(b) Z. Li and K. B. Grant, RSC Adv. 2016, 6, 24617.
59
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