Dalton Transactions
Paper
(126 MHz, CDCl3) δ 169.59, 163.83, 134.05, 130.18, 128.65,
126.99, 61.26, 31.05, 26.21, 25.26 ppm. ESI-MS: m/z = 233.9
[M + H]+.
5 S. Dasari and P. B. Tchounwou, Eur. J. Pharmacol., 2014,
740, 364.
6 D. A. Tolan, Y. K. Abdel-Monem and M. A. El-Nagar, Appl.
Organomet. Chem., 2019, 33, e4763.
1
6a: H NMR (500 MHz, CDCl3) δ 8.71 (s, 1H), 8.09 (dd, J =
8.6, 1.6 Hz, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.93 (d, J = 8.8 Hz,
1H), 7.90 (d, J = 8.3 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.60–7.56
(m, 1H), 2.54 (t, J = 7.8 Hz, 2H), 2.14–2.10 (t, J = 7.8 Hz, 2H),
1.40 (s, 6H) ppm. 13C NMR (126 MHz, CDCl3) δ 172.09, 169.71,
7 Z. Wang, Z. Deng and G. Zhu, Dalton Trans., 2019, 48, 2536.
8 S. Dilruba and G. V. Kalayda, Cancer Chemother.
Pharmacol., 2016, 77, 1103.
9 O. Pinato, C. Musetti and C. Sissi, Metallomics, 2014, 6, 380.
164.06, 135.97, 132.11, 129.50, 128.90, 128.53, 127.86, 126.98, 10 (a) W. H. Ang, I. Khalaila, C. S. Allardyce, L. Juillerat-
125.21, 61.37, 31.92, 31.06, 29.69 ppm. ESI-MS: m/z = 284.0
Jeanneret and P. J. Dyson, J. Am. Chem. Soc., 2005, 127,
1382; (b) S. Dhar, F. X. Gu, R. Langer, O. C. Farokhzad and
S. J. Lippard, Proc. Natl. Acad. Sci. U. S. A., 2008, 105, 17356;
(c) M. Galanski and B. K. Keppler, Anticancer Agents Med.
Chem., 2007, 7, 55.
[M + H]+.
dGMP binding studies after photoreduction
The eluents used were 10 mM NH4OAc and MeOH. The
elution gradient was 5% MeOH to 7% MeOH from 0 to
20 min. The eluted peaks were collected at Rt of 6.1 min and
10.9 min for mono-dGMP adduct [Pt(NH3)2(dGMP)Cl] and bis-
dGMP adduct [Pt(NH3)2(dGMP)2], respectively, as analysed by
ESI-MS (Fig. S10 and S11†).
11 R. Oun, Y. E. Moussa and N. J. Wheate, Dalton Trans., 2018,
47, 6645.
12 C. N. Sternberg, P. Whelan, J. Hetherington,
B. Paluchowska, P. H. T. J. Slee, K. Vekemans, P. Van Erps,
C. Theodore, O. Koriakine, T. Oliver, D. Lebwohl,
M. Debois, A. Zurlo and L. Collette, Oncology, 2005, 68, 2.
13 M. D. Hall and T. W. Hambley, Coord. Chem. Rev., 2002,
232, 49.
14 F. S. Mackay, J. Woods, H. Moseley and P. J. Sadler,
Br. J. Dermatol., 2005, 152, 857.
15 L. Cubo, A. M. Pizarro, A. G. Quiroga, L. Salassa,
C. Navarro-Ranninger and P. J. Sadler, J. Inorg. Biochem.,
2010, 104, 909.
16 N. A. Kratochwil, M. Zabel, K. J. Range and P. J. Bednarski,
J. Med. Chem., 1996, 39, 2499.
17 P. Müller, B. Schröder, J. A. Parkinson, N. A. Kratochwil,
R. A. Coxall, A. Parkin, S. Parsons and P. J. Sadler, Angew.
Chem., Int. Ed., 2003, 42, 335.
18 J. S. Butler, J. A. Woods, N. J. Farrer, M. E. Newton and
P. J. Sadler, J. Am. Chem. Soc., 2012, 134, 16508.
19 L. A. Wickramasinghe and P. R. Sharp, Inorg. Chem., 2014,
53, 11812.
Conclusions
In summary, we report a new class of Pt(IV) complexes contain-
ing aryl carboxylate ligands designed as UV-activatable pro-
drugs. The carboxylate ligands were positioned at the axial sites,
in contrast to other examples, with the goal of stabilising
radical carboxyl species after irradiation. We demonstrated that
photoinduced ligand dissociation occurs via formation of aryl
carboxyl radicals and that reactive Pt(II) species mirroring cDDP
reactivity was formed. We are optimistic that by further tuning
the nature of the axial carboxylate ligands, the strategy can be
extended to access other Pt(IV) constructs that would generate
cDDP across a wider range of the electromagnetic spectrum.
Conflicts of interest
20 L. A. Wickramasinghe and P. R. Sharp, Organometallics,
2015, 34, 3451.
21 T. A. Perera, M. Masjedi and P. R. Sharp, Inorg. Chem.,
2014, 53, 7608.
There are no conflicts to declare.
22 T. Grégory, J. F. Arambula, Z. H. Siddik and J. L. Sessler,
Chem. – Eur. J., 2014, 20, 8942.
Acknowledgements
23 J. Kasparkova, H. Kostrhunova, O. Novakova, R. Křikavová,
J. Vančo, Z. Trávníček and V. Brabec, Angew. Chem., Int. Ed.,
2015, 54, 14478.
24 V. Maurel;, J.-L. Ravanat; and S. Gambarelli, Rapid
Commun. Mass Spectrom., 2006, 20, 2235.
We acknowledge financial support from Singapore Ministry of
Education (R143-000-A53-114). V. E. Y. L. acknowledges scho-
larship and support from NUS Graduate School for Integrative
Sciences and Engineering (NGS).
25 B.-Z. Zhu, G.-Q. Shan, C.-H. Huang, B. Kalyanaraman,
L. Mao and Y.-G. Du, Proc. Natl. Acad. Sci. U. S. A., 2009,
106, 11466.
Notes and references
1 L. Kelland, Nat. Rev. Cancer, 2007, 7, 573.
26 L. J. Berliner, Appl. Magn. Reson., 2009, 36, 157.
2 A. Horwich, J. Shipley and R. Huddart, Lancet, 2006, 367, 27 J. D. Gralla, S. Sasse-Dwight and L. G. Poljak, Cancer Res.,
754.
1987, 47, 5092.
3 Y. Jung and S. J. Lippard, Chem. Rev., 2007, 107, 1387.
4 D. Wang and S. J. Lippard, Nat. Rev. Drug Discovery, 2005, 4,
307.
28 U. Warnke, C. Rappel, H. Meier, C. Kloft, M. Galanski,
C. G. Hartinger, B. K. Keppler and U. Jaehde,
ChemBioChem, 2004, 5, 1543.
This journal is © The Royal Society of Chemistry 2019
Dalton Trans.