Adenine–adenine, adenine–cytosine and cytosine–cytosine intrastrand crosslinks induced by a photoactivatable Pt(iv) anticancer prodrug

Abstract

Four trinucleotides 5′-ATA-3′ (I), 5′-ATC-3′ (II), 5′-CTA-3′ (III) and 5′-CTC-3′ (IV) were introduced to interact with a diazido-based photoactivatable anticancer prodrug trans,trans,trans-[Pt^IV(N₃)₂(OH)₂(py)₂] (py = pyridine; 1) upon light irradiation. Using electrospray ionization mass spectrometry (ESI-MS), we aimed to investigate the possibility of 1,3-intrastrand crosslinks at adenine and/or cytosine in the trinucleotides via the bi-functional trans-[Pt^II(py)₂]²⁺ species generated by photodecomposition of complex 1. The primary mass spectrometry results showed that although mono- and di-platinated trinucleotides bound by mono-functional trans-[Pt^II(N₃)(py)₂]⁺ species were the major platinated adducts, comparable amounts of bifunctional trans-[Pt^II(py)₂]²⁺-bound trinucleotides were also observed. Further tandem mass spectrometry of the trans-[Pt^II(py)₂]²⁺-bound trinucleotides showed the formation of 1,3-crosslinks between adenine–adenine, adenine–cytosine and cytosine–cytosine bases in the trinucleotides. The formation of such unique structures is not only distinct from the action modes of cisplatin with DNA but also an important complement to the acknowledged 1,3-GNG intrastrand crosslink by trans-Pt species, which may support the promising and distinct anticancer activities of such photoactivatable diazido Pt(IV) anticancer prodrugs and deserve further studies.