A visible-light photoactivatable di-nuclear PtIV triazolato azido complex

Article abstract of DOI:10.1039/c9cc05310g

A novel Pt^IV triazolato azido complex [3]-[N1,N3] has been synthesised via a strain-promoted double-click reaction (SPDC) between a Pt^IV azido complex (1) and the Sondheimer diyne (2). Photoactivation of [3]-[N1,N3] with visible ligh

Full text of DOI:10.1039/c9cc05310g

ChemComm
View Article Online
View Journal
COMMUNICATION
IV
A visible-light photoactivatable di-nuclear Pt
triazolato azido complex†
Cite this:DOI: 10.1039/c9cc05310g
Kezi Yao, Arnau Bertran, Alison Howarth, Jose M. Goicoechea,
Samuel M. Hare,
Received 10th July 2019,
Accepted 30th July 2019
Nicholas H. Rees, Mohammadali Foroozandeh,
Nicola J. Farrer
Alice M. Bowen and
*
DOI: 10.1039/c9cc05310g
rsc.li/chemcomm
IV
A novel Pt triazolato azido complex [3]-[N1,N3] has been synthesised azido complexes with both electron-deficient (e.g. 1,4-diphenyl-2-
IV
15
via a strain-promoted double-click reaction (SPDC) between a Pt
butyne-1,4-dione) and strained alkynes (e.g. DBCO; dibenzocyclo-
16
azido complex (1) and the Sondheimer diyne (2). Photoactivation of octyne-amine). Due to the popularity of click chemistry, a range
3]-[N1,N3] with visible light (452 nm) in the presence of 5 -guanosine of 1,2,3-triazoles with potential biomedical applications have been
0
[
0
IV
II
0
17–19
monophosphate (5 -GMP) produced both Pt and Pt 5 -GMP species; reported;
1,2,3-triazoles have the potential to participate in
EPR spectroscopy confirmed the production of both azidyl and C–H hydrogen bonding; behave as hydrogen bond donors
hydroxyl radicals. Spin-trapping of photogenerated radicals – through both non-coordinated N-atoms; act as intercalating
particularly hydroxyl radicals – was significantly reduced in the agents via p–p stacking and substitute for amides; making them
0
20
II
21
presence of 5 -GMP.
attractive ligands. Pt triazole complexes and triazolato-
II
bridged Pt complexes have been shown to demonstrate
Of the cancer patients who are treated with chemotherapy, approxi- promising anti-cancer activity.
Strain-promoted azide–alkyne [3+2] cycloaddition (SPAAC)
oxaliplatin. However, the side-effects of treatment with Pt drugs exploits the spontaneous reactivity of cyclooctynes and azides
can be severe, and the development of resistance can also be a due to inherent ring strain in the cyclooctyne. It can be used
serious problem. Octahedral low-spin 5d Pt prodrugs are more to assemble constructs under mild conditions for both bio-
kinetically inert than their Pt counterparts, and have the potential logical (e.g. vascularly-targeted radiolabelled liposomes, glycan
to address these issues. Both redox-activatable and photo- imaging and glycocalyx selective editing ) and chemical (e.g.
2
2
II
mately 50% receive a Pt drug such as cisplatin, carboplatin or
1
II
2
3
2
6
IV
II
24
3
–6
7,8
25
26
9
–12
IV
27
II
28
activatable
Pt prodrugs can exhibit promising pharmaco- Ru azido DBCO and Pt -DBCO fluorophore ) applications.
The Sondheimer diyne (5,6,11,12-tetradehydrodibenzo[a,e]-
released upon reduction of Pt to Pt – exert an anti-cancer cyclooctene) (2) (Scheme 1) is a strained diyne which is
logical properties and can also incorporate ligands which - when
IV
II
effect through mechanisms of action which are different from straightforward to synthesise. It has been used as a monomer
II
5,13
those of established Pt -based drugs.
in Mo-catalysed ring-opening alkyne metathesis polymerization
IV
29
30
Whilst the photochemistry of Pt diazido complexes has reactions
been extensively investigated, Pt monoazido complexes are biomolecules. For our purposes, it enables the union of two –
less well explored. It was not known if two azido groups are potentially different – Pt azido complexes under catalyst-free
necessary for photoreduction to Pt , and what products were conditions, without interaction of either Pt centre with any
likely to be formed under irradiation. Direct derivation of a Pt
diazido complex was anticipated to be an effective way to
answer these questions. Cycloaddition (click) reactions of metal
azido complexes are well-established – although mostly for Pt
rather than Pt . We recently reported the first Pt triazolato
and to couple together Ag(I) species
and
IV
31
IV
II
IV
IV
other functional groups on the newly formed 1,2,3-triazole
1
4
II
IV
IV
IV
monoazido complexes; synthesised via click reactions of Pt
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford,
OX1 3TA, UK. E-mail: Nicola.Farrer@chem.ox.ac.uk; Tel: +44 (0)1865 285131
†
Electronic supplementary information (ESI) available: Synthetic details and
characterisation data including X-ray crystallographic tables. CCDC 1885195 con-
tains the supplementary crystallographic data for this paper. For ESI and crystal-
lographic data in CIF or other electronic format see DOI: 10.1039/c9cc05310g
IV
Scheme 1 Synthesis of Pt triazolato azido complex (3)-[N1,N3].
This journal is ©The Royal Society of Chemistry 2019
Chem. Commun.

View Article Online
Communication
ChemComm
ligands – something which has complicated our earlier
1
5,16
IV
studies.
Di-nuclear Pt complexes are promising since they
can be used to deliver multiple different biologically active
8
agents to cancer cells. Here we report the facile, catalyst-free
IV
assembly of the water-soluble, water-stable, di-nuclear Pt
1,2,3-triazolato azido complex 3-[N1,N3] and our investigations
into its photochemical properties (Scheme 1).
Diyne (2) was synthesised according to literature reports and
3
2,33
purified by column chromatography (ESI†).
Pt(N (OH) (py) ] (1) was synthesised and purified by HPLC.
The reaction between 1 (200 mg, 0.42 mmol) and 2 (30 mg,
.15 mmol, 0.4 eq.) in MeCN (150 ml) at room temperature was
trans,trans,trans-
3
4
[
)
3 2
2
2
0
monitored by LCMS and was judged to be complete after 2d. No
IV
mono-Pt cycloaddition intermediates were detected by ESI-MS
during the course of the reaction. This is consistent with DFT
Fig. 1 X-ray crystallographic structure of 3-[N1,N3] with thermal ellipsoids
displayed at 50% probability. Selected bond lengths (Å): Pt1–N3: 2.060(2),
35
calculations of the reactivity profile of 2, which indicate that the Pt1–N7: 2.041(3), N7–N8: 1.219(4), N8–N9: 1.151(5). Pt1–O2: 2.002(2).
Selected angles (1): Pt1–N7–N8: 114.1(2); N7–N8–N9: 174.5(4). (See
Tables S1–S3, ESI†).
activation energy for the second cycloaddition is lower than for
the first, due to the highly distorted alkyne bond in the mono-
substituted intermediate, arising from steric repulsion between
the substituent on the triazole ring and the hydrogen atom
3
1
+
on the benzene ring. The reaction solution was dilute, observed, including [Pt(C16
N
6
H
7
)N
3
]
(520.15 m/z) resulting
IV
minimising the formation of Pt oligomers (see Fig. S1, ESI†) from ejection of several small ligands and one Pt fragment from
IV
due to potential reactivity of the second Pt -azido ligand.
the central cyclooctene ligand, as well as smaller fragments including
+
+
The major product (3) was detected by LCMS, as both ([Pt(py)
2
(OH)
2
]
(387.12 m/z)) ([Pt(py)
2
(OH)] (370.11 m/z)) and
] (352.10 m/z)) demonstrating cleavage of the Pt–triazole
+
+
+
[
3 + H] (1143.20 m/z) and [3 + Na] (1165.36 m/z) adducts. ([Pt(Py)
2
Complex 3 was isolated by mass-directed LCMS as a mixture of bond (Fig. S7, ESI†).
1
95
1
two regioisomers: 3-[N1,N3] and 3-[N3,N3] (Fig. S2, ESI†). HPLC
re-injection confirmed the isomers co-eluted with a purity of
Complex 3-[N1,N3] was fully characterised by
C NMR spectroscopic methods. H NMR spectroscopy
Pt, H and
1
3
1
1
9
5% (Fig. S3, ESI†). Following solvent removal and reconstitution revealed four different phenyl environments; a 2D H TOCSY
1
3
of the pale yellow solid in d -MeCN, H NMR spectroscopy experiment was used to determine the complete spin systems
indicated that 3-[N1,N3] – which has two-fold symmetry – was and to obtain coupling constants for overlapping signals
the major isomer present. This is consistent with the previously (Fig. S9, ESI†) and 1D NOESY experiments revealed nOe inter-
reported reaction of 2 with excess benzyl azide which resulted in a actions between pyridine (H ) and phenyl ring (H ) protons,
o A
3
1
6
0% [N1,N3]: 38% [N1,N1] product distribution. Yellow crystals confirming the regiochemistry of the product (Fig. S10, ESI†).
1
3
of 3-[N1,N3] rapidly formed from the solution of regioisomers in
d3-MeCN, on standing for 24 h.
C NMR spectral assignment (Fig. S11, ESI†) was aided by
1
13
H– C HSQC and HMBC experiments. Complex 3-[N1,N3] gave
1
95
Recrystallisation from MeCN afforded X-ray crystallographic rise to a single
Pt NMR spectral resonance at 723 ppm
quality crystals of 3-[N1,N3] (Fig. 1), confirming [N1,N3] (d
Pt -triazole coordination and revealing the ligand interactions
3
-MeCN, Fig. S12-top, ESI†).
Whilst 3-[N1,N3] is stable in both d -MeCN and D O for a
3 2
IV
1
around the puckered chair of the cyclooctene ligand. Distances period of at least 5 weeks as judged by H NMR spectroscopy,
between pyridine, triazole and benzene groups are shown in the resonances change position markedly in the different
Fig. S4–S6 (ESI†); the pyridine ligands undergo p–p interactions solvents. Solvent removal from a sample of 3-[N1,N3] in
with the cyclooctene ring ranging from 3.527–4.509 Å in length. d -MeCN followed by reconstitution in D O resulted in an overall
3
2
1
95
A hydrogen-bond interaction of 2.178(3) Å was observed 163 ppm upfield shift in
Pt NMR resonance from 723 ppm
between Pt(1)–OH(2) and triazole N(2); the corresponding (d
hydrogen-bond interaction on the other side of the molecule Fig. S12-bottom, ESI†). In the H NMR spectrum (D
measured 2.242 Å (Pt–OH(3) to triazole N(5)). The identity of 3 and H protons of the benzene rings no longer superimposed
H): on the pyridyl H resonances (Fig. S13 and S14, ESI†). Consistent
3
-MeCN) to 857 ppm (1: 1 d
3
1
-MeCN : D
2
O) to 886 ppm (D
2
O,
2
O), the H
A
0
0
B
+
was also confirmed by HRMS [3 + H] (C36
143.2123 m/z found; 1143.2069 m/z calcd (Fig. S7, ESI†).
Collision-induced dissociation (MS/MS) experiments of [3- on changing solvent from d
H
32
N
16
O
4
Pt
2
m
195
1
with this, the Pt NMR resonance of 1 also changes by 164 ppm
-MeCN (778 ppm, this work) to
3
1
+
34
[
N1,N3] + H] demonstrated that at low collision energies the D O (942 ppm). Selective H NOESY NMR experiments on
2
complex readily fragmented through loss of OH and N ligands, 3-[N1,N3] (D O) revealed the same nOe correlations which
3
2
+
to give stable species [3-[N1,N3]–N OH + H] (1083.32 m/z) were observed in d
3
-MeCN, with dissolution in 1 : 1 MeCN/D
OH)] , (1023.30 m/z), consistent with our showing H NMR resonances at intermediate chemical shifts
previous observations of azido ligand loss during MS/MS (Fig. S14-middle, ESI†), indicating that the change is unlikely to
2
O
3
+
1
and [3-[N1,N3]–2(N
3
3
4
2
fragmentation of 1. Stable mono-Pt fragments were also be due to a formal N1–N2 Pt–triazole rearrangement in D O – a
Chem. Commun.
This journal is ©The Royal Society of Chemistry 2019

View Article Online
ChemComm
Communication
possibility for metal triazole complexes which we wanted to
2
7,36,37
rule out.
IR spectroscopy of a d -MeCN sample of 3-[N1,N3] (Fig. S15,
3
ꢀ1
ESI†) showed a strong nasymN stretch at 2043 cm ; slightly
3
ꢀ
1
38
lower than observed for 1 (2051 cm , solid). The UV-Vis
spectrum of 3-[N1,N3] showed a long shoulder with lmax
ca. 254 nm tailing into the visible region corresponding to
3
the N - Pt LMCT transition band, with increased intensity
at shorter wavelengths compared to 1 due to the additional
aromatic groups (Fig. S16, ESI†).
A D O (1 ml) solution of complex (3)-[N1,N3] (5.6 mg)
2
0
and the DNA model 5 -GMP (2 eq. 4.8 mg) was irradiated
1
(
lirr 452 nm) with regular monitoring by LCMS and H NMR
IV
II
spectroscopy. Both Pt and Pt photoproducts were detected by
LCMS including non-5 -GMP bound species (where M = 3-[N1,N3]):
] at 1100.12 m/z; [M–H O + H] at 1109.12 m/z; [3-[N1,N3]–
3 2 2
OH + H ] 1084.05 m/z. The cyclic-5 -GMP species [Pt (OH)-
0
+
+
[M–N
+
+
0
II
N
3
+
(py)
2 5 10 7
(N C O H12P)] was observed at 715.14 m/z, although – unlike
for similar investigations with complex 1 – no evidence of
0
Pt(OH)(py) (5 -GMP)] was observed (predicted 733.1097 m/z).
2
+
[
The LCMS m/z range is limited to 1250 m/z and a different
ESI-MS instrument was therefore used to detect the presence
II
of higher mass species, including the Pt bis-GMP adduct:
0
+
[
M–2(H
2
O
2
)–2N
3
+ 2(5 -GMP) + Na] at 1739.85 m/z. (Fig. S17, ESI†).
1
195
The photochemistry was also monitored by H– Pt HMBC
1
95
0
Pt NMR spectroscopy ((3)-[N1,N3] 22 mM; 5 -GMP
and 1D
4
6 mM, 1 : 1 D O : d -MeCN, l 452 nm, 180 min). During
2 3 irr
1
95
irradiation, the intensity of the
Pt NMR spectroscopic
resonance corresponding to (3)-[N1,N3] (854 ppm) decreased,
IV
with small amounts of new Pt species (1267, 1350 ppm) and two
II
more intense Pt signals appearing (ꢀ2224 ppm and ꢀ2369 ppm;
ꢁ
Fig. 2 X-band cw-EPR spectrum (a) showing trapping of azidyl (N
3
) and
Fig. S18 and S19, ESI†). These spectra were consistent with the
ꢁ
II
IV
hydroxyl (OH ) radicals (1.15 mM (3)-[N1,N3] + 20 mM DMPO spin-trap) in
freshly prepared KNS42 lysate (lirr 440–480 nm; spectra averaged over 1 h
of maximum signal intensity); (b) fitted spectrum with 90% DMPO-N and
3
formation of multiple Pt and Pt photoproducts, as observed by
LCMS (for discussion see end of ESI†).
Irradiation of a solution of 3-[N1,N3] (1.15 mM) and 10% DMPO-OH (red line). The kinetic profile (b) for the total radical adduct
,5-dimethyl-1-pyrroline N-oxide (DMPO, 20 mM) monitored signal (black) has been deconvoluted into the DMPO-N (blue) and DMPO-OH
5
3
(red) contributions.
by EPR spectroscopy in either water or cell-free lysate (KNS42)
ꢁ
ꢁ
generated azidyl (N
trapped in a 85 : 15 and 90 : 10 molar ratio, respectively (Fig. S20(a),
ESI† and Fig. 2(a)), with a maximum trapped radical concentration kinetics in the presence of 5 -GMP. Minimal radical release was
3
) and hydroxyl (OH ) radical species,
0
of 7 mM. The signals started to decay after B30 min irradiation observed in the absence of irradiation in aqueous solution, con-
0
(
Fig. S23(a), ESI† and Fig. 2(b)). The inclusion of 5 -GMP in the sistent with the observed stability of 3-[N1,N3] and 1 (Fig. S26,
0
solution of 3-[N1,N3] in lysate had a significant effect; the ESI†). Irradiation of controls (DMPO, and 5 -GMP + DMPO) in
maximum trapped radical concentration reduced to 3 mM with lysate did not result in any trapped radicals (Fig. S27, ESI†).
a 95 : 5 N3 : OH molar ratio (Fig. S22(a), ESI†) and radical
trapping slowed down (Fig. S25(a), ESI†). These experiments joining together two Pt azido complexes to give the di-nuclear
were repeated with complex 1 (Fig. S20(b), S21(b) and S22(b), Pt triazolato azido complex 3-[N1,N3] which is soluble and
ꢁ
ꢁ
To conclude, we have demonstrated an effective method for
IV
IV
ESI†) which released almost no hydroxyl radicals, reaching a stable in aqueous solution for at least 5 weeks. Irradiation
much higher trapped radical maximum concentration of 32 mM of 3-[N1,N3] with visible light (lirr 452 nm) in the presence of
0
IV
II
in water and lysate. The rise and decay of the signal was faster 5 -GMP results in the formation of new Pt and Pt species as
(
ꢁ ꢁ
Fig. S23(b) and S24(b), ESI†) in comparison to 3-[N1,N3], well as radical species (N , OH ) in both H O and cell-free
3 2
consistent with 1 having a greater absorbance at the wavelength lysate. Whilst the presence of two Pt-azido groups in complex 1
0
of irradiation. The effect of including 5 -GMP in the lysate predominantly favours photochemical release of azido radicals,
II
solution of complex 1 was less pronounced (Fig. S22(b) and 3-[N1,N3] undergoes photoreduction to Pt with the production
S25(b), ESI†) than for 3-[N1,N3], with only a slightly lower of a greater proportion of hydroxyl radicals, consistent with the
IV
ꢁ
maximum trapped radical concentration (28 mM) and slower Pt monoazido structure. Radical – particularly OH – trapping
This journal is ©The Royal Society of Chemistry 2019
Chem. Commun.

View Article Online
Communication
ChemComm
from 3-[N1,N3] was affected to a greater extent by the presence 13 J. J. Wilson and S. J. Lippard, Chem. Rev., 2014, 114, 4470.
0
14 W. P. Fehlhammer and W. Beck, Z. Anorg. Allg. Chem., 2015,
41, 1599.
15 K. Yao, A. Bertran, J. Morgan, S. M. Hare, N. H. Rees, A. M. Kenwright,
K. Edkins, A. M. Bowen and N. J. Farrer, Dalton Trans., 2019, 48, 6416.
16 N. J. Farrer, G. Sharma, R. Sayers, E. Shaili and P. J. Sadler, Dalton
Trans., 2018, 47, 10553.
of 5 -GMP, in contrast to irradiation of 1. It has previously been
6
ꢁ
shown that N3 produced by irradiation of 1 can be quenched
by L-tryptophan (Trp), forming Trp radicals; our future work
will investigate the interaction of hydroxyl radicals with 5 -GMP
and the possible photocytotoxicity of 3-[N1,N3].
3
9
40
0
17 D. Dheer, V. Singh and R. Shankar, Bioorg. Chem., 2017, 71, 30.
We thank the Wellcome Trust (201406/Z/16/Z), Cancer 18 E. Bonandi, M. S. Christodoulou, G. Fumagalli, D. Perdicchia,
G. Rastelli and D. Passarella, Drug Discovery Today, 2017, 22, 1572.
Research UK (C5255/A18085) through the Cancer Research
1
2
9 B. Schulze and U. S. Schubert, Chem. Soc. Rev., 2014, 43, 2522.
0 A. Massarotti, S. Aprile, V. Mercalli, E. Del Grosso, G. Grosa, G. Sorba
and G. C. Tron, ChemMedChem, 2014, 9, 2497.
1 A. Maisonial, P. Serafin, M. Tra ¨ı kia, E. Debiton, V. Th ´e ry, D. J.
Aitken, P. Lemoine, B. Viossat and A. Gautier, Eur. J. Inorg. Chem.,
UK Oxford Centre, the John Fell Fund and L’Or ´e al (Women in
Science Fellowship). NF thanks Prof. Stephen Faulkner and
Prof. Andy Weller for helpful discussions and Dr Richard Hill
and Prof. Chris Jones for the KNS42 cell line. EPR measurements
2
2008, 298.
were performed in the Centre for Advanced Electron Spin Resonance 22 S. Komeda, M. Lutz, A. L. Speck, M. Chikuma and J. Reedijk, Inorg.
at the University of Oxford EPSRC (EPL011972/1). AMB thanks the
Royal Society and EPSRC for a Dorothy Hodgkin Fellowship
Chem., 2000, 39, 4230.
2
2
3 J. C. Jewett and C. R. Bertozzi, Chem. Soc. Rev., 2010, 39, 1272.
4 E. D. Hood, C. F. Greineder, T. Shuvaeva, L. Walsh, C. H. Villa and
V. R. Muzykantov, Bioconjugate Chem., 2018, 29, 3626.
(DH160004); AMB and AB thank the Royal Society for a Grant
for Research Fellows (RGF\R1\180099). MF thanks the Royal 25 H. Sto¨
ckmann, A. A. Neves, S. Stairs, H. Ireland-Zecchini,
K. M. Brindle and F. J. Leeper, Chem. Sci., 2011, 2, 932.
6 H. Xiao, E. C. Woods, P. Vukojicic and C. R. Bertozzi, Proc. Natl.
Acad. Sci. U. S. A., 2016, 113, 10304.
Society for a University Research Fellowship and an Enhancement
Award (grant numbers URF\R1\180233 and RGF\EA\181018).
2
2
2
7 T. Cruchter, K. Harms and E. Meggers, Chem. – Eur. J., 2013, 19, 16682.
8 E. Kitteringham, D. Wu, S. Cheung, B. Twamley, D. F. O’Shea and
D. M. Griffith, J. Inorg. Biochem., 2018, 182, 150.
Conflicts of interest
2
3
3
9 W. S. Perkins, S. von Kugelgen, F. R. Fischer, R. R. Cloke and
There are no conflicts to declare.
D. E. Bellone, J. Am. Chem. Soc., 2016, 138, 6234.
0 B. Hellbach, F. Rominger and R. Gleiter, J. Organomet. Chem., 2006,
691, 1814.
Notes and references
1 I. Kii, A. Shiraishi, T. Hiramatsu, T. Matsushita, H. Uekusa,
S. Yoshida, M. Yamamoto, A. Kudo, H. Masatoshi and T. Hosoya,
Org. Biomol. Chem., 2010, 8, 4051.
1
M. Galanski, M. A. Jakupec and B. K. Keppler, Curr. Med. Chem.,
005, 12, 2075.
2
3
3
3
2 H. N. C. Wong, P. Garratt and F. Sondheimer, J. Am. Chem. Soc.,
2
3
4
R. Oun, Y. E. Moussa and N. J. Wheate, Dalton Trans., 2018, 47, 6645.
D. Gibson, J. Inorg. Biochem., 2019, 191, 77.
M. Ravera, E. Gabano, M. J. McGlinchey and D. Osella, Inorg. Chim.
Acta, 2019, 492, 32.
1
974, 96, 5604.
3 A. Orita, D. Hasegawa, T. Nakano and J. Otera, Chem. – Eur. J., 2002,
, 2000.
8
4 N. J. Farrer, J. A. Woods, L. Salassa, Y. Zhao, K. S. Robinson,
5
6
7
8
9
R. G. Kenny, S. W. Chuah, A. Crawford and C. J. Marmion,
Eur. J. Inorg. Chem., 2017, 1596.
T. C. Johnstone, K. Suntharalingam and S. J. Lippard, Chem. Rev.,
G. Clarkson, F. S. Mackay and P. J. Sadler, Angew. Chem., Int. Ed.,
2010, 49, 8905.
35 O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and
H. Puschmann, J. Appl. Crystallogr., 2009, 42, 339.
2
016, 116, 3436.
K. G. Z. Lee, M. V. Babak, A. Weiss, P. J. Dyson, P. Nowak-Sliwinska,
D. Montagner and W. H. Ang, ChemMedChem, 2018, 13, 1210.
E. Petruzzella, J. P. Braude, J. R. Aldrich-Wright, V. Gandin and
D. Gibson, Angew. Chem., Int. Ed., 2017, 56, 11539.
S. Perfahl, M. M. Natile, H. S. Mohamad, C. A. Helm, C. Schulzke,
G. Natile and P. J. Bednarski, Mol. Pharmaceutics, 2016, 13, 2346.
3
6 P. Schmid, M. Maier, H. Pfeiffer, A. Belz, L. Henry, A. Friedrich,
F. Sch o¨ nfeld, K. Edkins and U. Schatzschneider, Dalton Trans., 2017,
46, 13386.
37 K. S. Singh, K. A. Kreisel, G. P. A. Yap and M. R. Kollipara,
J. Organomet. Chem., 2006, 691, 3509.
1
1
1
0 H. C. Tai, Y. Zhao, N. J. Farrer, A. E. Anastasi, G. Clarkson, P. J. 38 R. R. Vernooij, T. Joshi, E. Shaili, M. Kubeil, D. R. T. Appadoo, E. I.
Sadler and R. J. Deeth, Chem. – Eur. J., 2012, 18, 10630.
1 I. Infante, J. M. Azpiroz, N. G. Blanco, E. Ruggiero, J. M. Ugalde,
Izgorodina, B. Graham, P. J. Sadler, B. R. Wood and L. Spiccia, Inorg.
Chem., 2016, 55, 5983.
J. C. Mareque-Rivas and L. Salassa, J. Phys. Chem. C, 2014, 118, 8712. 39 J. S. Butler, J. a Woods, N. J. Farrer, M. E. Newton and P. J. Sadler,
2 G. J. Clarkson, J. Song, V. Venkatesh, I. Romero-Canel ´o n, H. Shi,
V. Brabec, O. Novakova, P. J. Sadler, M. Hreusova and A. Habtemariam, 40 C. Vallotto, E. Shaili, H. Shi, J. S. Butler, C. J. Wedge, M. E. Newton
Inorg. Chem., 2018, 57, 14409.
and P. J. Sadler, Chem. Commun., 2018, 54, 13845.
J. Am. Chem. Soc., 2012, 134, 16508.
Chem. Commun.
This journal is ©The Royal Society of Chemistry 2019