A Phthalocyanine‐ortho‐Carborane Conjugate for Boron Neutron Capture Therapy: Synthesis, Physicochemical Properties, and in vitro Tests

Abstract

Boronated molecular systems can be applied to boron neutron capture therapy (BNCT). Among these systems, carboranecontaining phthalocyanines (Pcs) are the most promising BNCT agents. Herein we report the new zinc (II) complex of the hexacationic Pc 6, which has been obtained as iodide salt through quaternization of the neutral precursor with methyl iodide. Compound 6 was synthesized over a sequence of four steps. The complex, and its precursors as well, were characterized by a combination of spectroscopic techniques, and their structures assessed by 1 H, 13 C, 11 B, and two-dimensional NMR spectroscopy experiments. Together with a marked tendency to aggregate, 6 showed appreciable solubility in water. Singlet oxygen quantum yield (Φ Δ ) of 0.38, and fluorescence quantum yield (Φ F ) of 0.13 were obtained for 6 in a DMF solution. The complex proved to be very effective in enriching UMR-106 cells with 10 B, showing very good performance even in case of very low concentrations exposure, i. e. 1 ppm, that moreover resulted in a mild cytotoxic effect. Such a feature can be related to the polycationic nature of the complex, and hence to the wellknown propensity of positively charged species to enter the cellular membrane or to adhere to its external surface.

Carboranes as unique pharmacophores in antitumor medicinal chemistry

“… 165 In this context, a water-soluble, o -carborane-derived PC complex ( 29 ) was designed and obtained by Hamuryudan and co-workers. 166 Carboranes served as the boron source of BNCT while PC played a role in PDT activation ( Figure 5 B). This combination greatly enhances tumor killing efficiency.…”

Ru(ii) and Ir(iii) phenanthroline-based photosensitisers bearingo-carborane: PDT agents with boron carriers for potential BNCT

“…The 1 O2 quantum yield for RuCB is similar or higher to those reported for carboranecontaining phthalocyanines. [103][104][105][106] Importantly, photosensitisers used in clinical studies report φΔ values as low as 11 % (in H2O). 107,108…”

Pegylated metal-free and zinc(ii) phthalocyanines: synthesis, photophysicochemical properties andin vitrophotodynamic activities against head, neck and colon cancer cell lines

“…5 The most common method used to make Pcs biocompatible is based on the addition of hydrophilic or amphiphilic substituents to the periphery or the core of Pcs such as quaternized amines, pyridinium ions, carboxylates, sulfonates, phosphonates, hydroxyl groups, peptides, carbohydrates, and polyethylene glycol (PEG) groups. [6][7][8][9][10][11][12][13][14] Polyethylene glycols are hydrophilic, synthetic, and biocompatible polyether compounds with the general formula H-(O-CH 2 -CH 2 ) n -OH, which have a wide range of uses from biomedical and chemical applications to various fields of industry. 15 Some examples of Pcs containing PEG chains terminated with hydroxyl groups (PEGOH) and methyl ether groups (PEGOMe) have been previously reported.…”