Diazido platinum

Fig. 3. Photoactivation of Pt(IV) complexes as a prodrug strategy for metallochemotherapeutics (a) general scheme of prodrug activation by photoreduction (b) photosubstitution and photoisomerization are competing photoreaction pathways, which can result in different reactive species upon reduction (c) an example of a photoactive platinum(IV) diazido complex developed in our lab.

Fig. 5. Originally perceived, possible mechanism for photoactivation of platinum(IV) diazido complexes.

Fig. 7. Effect of light on the IC50 values for the inhibition of cell growth of various cancer cell lines by platinum(IV) diazido complexes, (a) toxicity of the cis-complexes 4 and 5 on human bladder cancer cell lines (5637-CDDP, cisplatin-resistant cell line) (b) comparison of cytotoxicities of the cis- and rarcs-isomers 4 and 6 in the dark and upon irradiation cisplatin is included for comparison. Data from Ref. (30).

It is important to note here that the activity of the platinum diazido complexes does not depend on the presence of oxygen, in contrast to conventional PDT, which is a potential advantage, as some tumors are oxygen-deficient. 

Alternatively, arene displacement can also be photo- rather than thermally-induced. In this respect, we studied the photoactivation of the dinuclear ruthenium-arene complex [ RuCl (rj6-indane) 2(p-2,3-dpp)]2+ (2,3-dpp, 2,3-bis(2-pyridyl)pyrazine) (21). The thermal reactivity of this compound is limited to the stepwise double aquation (which shows biexponential kinetics), but irradiation of the sample results in photoinduced loss of the arene. This photoactivation pathway produces ruthenium species that are more active than their ruthenium-arene precursors (Fig. 18). At the same time, free indane fluoresces 40 times more strongly than bound indane, opening up possibilities to use the arene as a fluorescent marker for imaging purposes. The photoactivation pathway is different from those previously discussed for photoactivated Pt(IV) diazido complexes, as it involves photosubstitution rather than photoreduction. Importantly, the photoactivation mechanism is independent of oxygen (see Section II on photoactivatable platinum drugs) (83). 

The University of Edinburgh (former employer of Peter J. Sadler) has filed patent applications relating to the ruthenium-arene, and platinum diazido complexes and University of Warwick for osmium-arene complexes under study in the Peter J. Sadler laboratory. 

Diazido-3-cyanoquinoline, see 2,4-Diazidoquinoline-3-carbonitrile, 3231c Diazido[(l,2,5,6-ri)-l,5-Cyclooctadiene]platinum, 3007... 

The stereoselective fram-diazidation occurred with cyclohexene to give fram-l,2-diazidocyclo-hexane (1), hydrogenation of the adduct 1 on platinum dioxide gives pure tram- 1,2-cyclohex-anediamine 28. The same method was applied to the preparation of irans-(5a,6/ )-diazido-steroids, for example, 38. Benzonorbornene underwent cxo-cw-addition73. 

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