Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings: 11 Photoactivity of a newPt(II)pentanuclear macrocycle bearing four cisplatin-like functionalities and its related monoplatinated species

Abstract

The pentanuclear PtII porphyrazine compound [(PtCl2)4LPt] (L = tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazinato dianion), the mononuclear species [LPt] and the octacation [L′Pt]8+ (neutralized by I- ions; L′ = L octaquaternized at the pyridine N atoms) were synthesized and characterized by IR/UV-visible spectral measurements. 1H and 13C NMR spectral data on [(PtCl2)4 LPt] indicate that the four PtCl2 units are coordinated at the pyridine N atoms of the peripheral dipyridinopyrazine fragments ("py–py" coordination) and the largely prevalent conformational arrangement of the entire macrocycle, established to have the external N2(py)PtCl2 coordination sites all oriented on the same side with respect to the plane of the central porphyrazine framework, closely recalls that which was previously defined for the related PdII analog [(PdCl2)4LPd] . The currently investigated triad of PtII macrocycles, like the related PdII species, behave as photosensitizers for the generation of singlet oxygen, the cytotoxic agent active in photodynamic therapy (PDT). A bimodal anticancer potentiality is expressed by the pentaplatinated compound, [(PtCl2)4LPt] , which represents an unprecedented example of a multifunctional drug due to the presence of four contiguous cisplatin-like functionalities.

Tetrapyrazinoporphyrazines and their metal derivatives. Part I: Synthesis and basic structural information

“…The Mg II macrocycle appears always formulated with one water molecule axially ligated to the central metal, in line with previous findings for the similarly formulated phthalocyanine and porphyrazine Mg II analogs [71,[214][215][216]. The Pd II and Pt II metal complexes, [TPyz42PzPd] and [TPyz42PzPt], were obtained by external demetallation of their respective pentanuclear species [207,210] (see below). Magnetic susceptibility and electronic paramagnetic resonance (EPR) measurements provided information on the electronic spin state of the complexes [TPyz42PzM] with M = Mn II , Co II , and Cu II [204].…”

“…mononuclear complexes [TPyz42PzM] (B) [204,207,209,210], the related quaternized octacations [Me 8 TPyz42PzM] 8+ (C) [206,207,209,210], the homo/hetero pentanuclear derivatives [(M'Cl 2 ) 4 TPyz42PzM] (D) [58,207,209,210], the neutral heterobinuclear [(M'Cl 2 )TPyz42PzM] (E) [56] and the externally monoplatinated quaternized hexacations, [(PtCl 2 )Me 6 TPyz42PzM] 6+ [56].…”

“…Variably from batch to batch for each single species the number of clathrated water molecules can reach 15-20 for macrocyclic unit. The UV-vis and fluorescence spectral response of the most of the macrocycles and their potentialities as photosensitizers for the generation of singlet oxygen ( 1 O 2 ), of interest in photodynamic therapy [53,56,58,59,209,210,213], and as bi-multimodal anticancer drugs [57,59] were also studied. The metal free macrocycle [TPyz42PzH 2 ] (A in Scheme 31) was obtained by direct cyclotetramerization of the dinitrile precursor Pyz42, in the presence of DBU [119].…”

“…[58] can be prepared from the mononuclear species [TPyz42PzM] either by heating with excess of Pd II or Pt II dichlorides in DMSO or in the milder experimental conditions by the reaction with an excess of the bisbenzonitrile complex [(PhCN) 2 PdCl 2 ] in CHCl 3 at ambient temperature. Detachment of the external PdCl 2 and PtCl 2 units from the homopentanuclear complexes [207,210] performed in basic media (pyridine, 3% NH 3 water solution) allowed obtaining the corresponding mononuclear complexes [TPyz42PzPd] [207] and [TPyz42PzPt] [210], from which the access was given by reaction with CH 3 I to the preparation of the respective octacations [Me 8 TPyz42PzPd] 8+ [207] and [Me 8 TPyz42PzPt] 8+ [210] (as iodide salts). Based again on 1D and 2D 1 H and 13 C NMR solution spectral data, it was confirmed that coordination of the external PdCl 2 and PtCl 2 units takes place at the pyridine N atoms of the dipyridylpyrazine fragments ("py-py'" coordination) in all the reported homo-and heteropentametallic macrocycles, as occurs in the bimetallic species described above.…”

“…12 A c c e p t e d M a n u s c r i p form present. Collected further information, mainly contributed by NMR spectral data, strongly indicated that the structural isomer 4:0, accompanied by a minor isomeric component (2:2 cis or trans), is largely prevalent in the majority for the reported tetrapalladated [209] and tetraplatinated compounds [58,210].…”