Tetra-2,3-Pyrazinoporphyrazines with Externally Appended Pyridine Rings 22 Synthesis, Physicochemical and Photoactivity Studies on In(III) Mono- and Heteropentanuclear Complexes.

Maria Pia Donzello,Pavel A Stuzhin,Claudio Ercolani,Giulia Capobianco,Ida Pettiti

doi:10.3390/molecules27030849

Abstract

The basic macrocyclic octapyridinotetrapyrazinoporphyrazine InIII complex of formula [Py8TPyzPzIn(OAc)]·8H2O, prepared by reaction of the free ligand [Py8TPyzPzH2]·2H2O with In(OAc)3, is a stable-to-air species of which the structure has been studied by its X-ray powder diffraction and mass spectra and characterization operated by IR and UV-visible spectral behavior. The complex has been further examined and proven to be of potential interest for its response as an anticancer agent in the field of photodynamic therapy (PDT), the value of ΦΔ = 0.55 (in DMF) being in the range of 0.4–0.6 at the level of similar phthalocyanine and porphyrazine analogs and qualifying the species as a highly efficient anticancer agent. Planned parallel types of investigation, including their photoactive behaviour in PDT, have been extended to the mononuclear octacation [(2-Mepy)8TPyzPzIn(OAc)]8+ (salted by iodide ions) and the heteropentanuclear derivatives [(M’Cl2)4Py8TPyzPzIn(OAc)]·xH2O (M’ = PdII, x = 8; PtII, x = 1)) and [{(Pd(CBT)2)4}Py8TPyzPzIn(OAc)]·19H2O (CBT = m-carborane-1-thiolate anion).

Highlights

Among our extensive studies on macrocyclic porphyrazine metal derivatives often finalized to explore their tendency to behave as active agents in photodynamic therapy (PDT), a well-known anticancer curative modality [1,2,3,4], we previously reported on the mononuclear complexes of formula [TTDPzMX] (TTDPz = tetrakis(thiadiazole)porphyrazinato anion) carrying centrally MX groups (MX = AlIIICl, GaIIICl, and InIIIOAc) (OAc = acetate anion) [5], and for the two AlIII and GaIII macrocycles relevant data were obtained as to their potential photoactivity in Photodynamic therapy (PDT) (Φ∆ respectively 0.35 and 0.69) [6]
It was found interesting to add to these findings those regarding a series of InIII related porphyrazine complexes, this allowing a comparison on the heavy metal effect along the triad of the AlIII, GaIII, InIII complexes and on the role played by the target macrocycle as a potential therapeutic agent in PDT
As established for the parallel series of tetrakis(thiadiazole)porphyrazines [TTDzPzMX] (M = AlIII, GaIII; X = Cl/M = InIII, X = octacation [(2-Mepy)8TPyzPzIn (OAc)), [5] schematically shown in Figure 3, and supported by the molecular arrangement of the corresponding AlIII and GaIII species both elucidated by X-ray work [5] and by the findings for other similar tetrapyrrolic macrocycles given in ref. [7] (Table 1), providing for all of them (M = AlIII, GaIII) a distance M-Ct of 0.3–0.4 Å, the InIII center in the present basic macrocycle is given as axially positioned and residing out of the Ct of the inner N4 coordination site probably only very slightly exceeding the value of 0.4 Å

Summary

Introduction

[Py8TPyzPzIn(OAc)]·8H2O (20.7 mg; 0.014 mmoli) and (C6H5CN)2PdCl2 (26.3 mg (0.069 mmoli) (molar ratio 1:4.8) were introduced in a flask (10 mL) containing CHCl3 (5 mL) and the mixture was kept under stirring a room temperature for 24 h and heated at 50 ◦C for 48 h. [Py8TPyzPzIn(OAc)]·8H2O (20.0 mg, 0.0137 mmoli) and e (C6H5CN)2PtCl2 (32.3 mg, 0.0685 mmoli) (molar ratio 1:5) were introduced in a flask (10 mL) containing CHCl3 (5 mL) and the mixture was kept under stirring at 65 ◦C for five days. [(PdCl2)4Py8TPyzPzIn(OAc)]·8H2O (14.8 mg, 0.0068 mmoli) and m-carborane-1-thiol (17 mg, 0.096 mmol; molar ratio 1:14) were introduced in a flask (10 mL) containing CH3CN (5 mL) and the mixture was heated under reflux with stirring at 90 ◦C. UV-visible solution spectra of the synthesized compounds were recorded with a Varian Cary 5E spectrometer using quartz cuvettes (1 cm).

Results and Discussion

DMF initial final

Conclusions