Water-soluble carboranyl-phthalocyanines for BNCT. Synthesis, characterization, and in vitro tests of the Zn(ii)-nido-carboranyl-hexylthiophthalocyanine

Abstract

The zinc(II) complex of the octa-anionic 2,3,9,10,16,17,23,24-octakis-(7-methyl-7,8-dicarba-nido-undeca-boran-8-yl)hexyl-thio-6,13,20,27-phthalocyanine (nido-[ZnMCHESPc]Cs8, 7) has been obtained in the form of caesium salt through mild deboronation of the neutral precursor, the closo-[ZnMCHESPc] complex, 6, with CsF. 6 has been synthesized, in turn, by heating a finely ground mixture of the appropriate phthalonitrile and zinc(II) acetate at 180.0 °C. The complexes have been characterized by elemental analyses, FT-IR, UV-visible absorption and fluorescence emission spectroscopy, and their structures were assessed by (1)H, (13)C, (11)B, and two-dimensional homo- and hetero-correlated NMR spectroscopy experiments. 7 showed appreciable solubility in water solution, together with a marked tendency to aggregate. Aggregation of 7 in the hydrotropic medium resulted in significant fluorescence quenching. Instead, fluorescence quantum yields (Φ(F)) of 0.14 and 0.08, and singlet oxygen quantum yields (Φ(Δ)) of 0.63 and 0.24 were obtained for 6 and 7, respectively, in a DMF solution. In vitro boron neutron capture therapy (BNCT) experiments, employing boron imaging techniques as implemented in qualitative and quantitative neutron autoradiography methods, showed that 7 is capable of increasing the boron concentration of two selected cancerous cell lines, the DHD/K12/TRb of rat colon adenocarcinoma and UMR-106 of rat osteosarcoma, with the large-size Cs(+) counter-ions used to neutralize the negatively charged carborane polyhedra not presenting a significant obstacle to the process. Taken together, BNCT and photophysical measurement results indicated that 7 is potentially suitable for bimodal or multimodal anticancer therapy.

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

“…The obtained fluorescence quantum yield in DMF was relatively small (Table ). However, the yield was comparable to that measured for neutral polycarboranyl‐Pcs, such as the closo ‐[ZnMCHESPc] complex (0.13 vs 0.14) …”

“…By virtue of the hydrophobicity of the o ‐carborane compounds, Pcs including o ‐carboranes are completely insoluble in water . To confer water‐solubility to carboranylphthalocyanines, two strategies can usually be employed: the addition of water‐solubilizing groups (carboxylate, amino or hydroxyl groups),, or the deboronation of the o ‐carborane clusters to afford the corresponding anionic nido ‐carboranes . Here, we synthesized the carboranylphthalocyanine 6 bearing positively charged quaternary ammonium water‐solubilizing groups.…”

Aloe vera gel influence on the micellization behavior of copolymer Pluronic F127: A potential photosensitizer carrier for topical application

“…The Φ Δ values were determined using ZnPC and using eq. (): where is the singlet oxygen quantum yield for ZnPC (Φ Δ = 0.67 in DMSO; k A and k ZnPc are the DPBF photobleaching rates in the presence of the gel sample and ZnPC, respectively; and I A ,abs and are the light absorption values for the gel sample and ZnPC (λ = 630 nm), respectively.…”

Synthesis and biological evaluation of a new series of ortho-carboranyl biphenyloxime derivatives

“…However, its successful application in the treatment of cancer patients still presents a challenge in medical research [ 12 ]. A major challenge in designing boron containing drugs for BNCT of cancer is the selective delivery of 10 B to the tumor as well as water solubility [ 13 ]. Our synthetic strategy was to use heterocyclic alkyl chains as a boron delivery system, the target molecules being the heterocyclic alkyl oxime chains in which the boron functionality was present as a ortho -carborane.…”