title: 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.
authors.affiliation: Dipartimento di Scienze, Università della Basilicata, Viale dell'Ateneo Lucano 10, 85100 Potenza, Italy. giampaolo.ricciardi@unibas.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietrangeli
authors.forename: Angela
authors.initials: A
authors.lastname: Rosa
authors.forename: Antonietta
authors.initials: A
authors.lastname: Pepe
authors.forename: Saverio
authors.initials: S
authors.lastname: Altieri
authors.forename: Silva
authors.initials: S
authors.lastname: Bortolussi
authors.forename: Ian
authors.initials: I
authors.lastname: Postuma
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Protti
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ferrari
authors.forename: Laura
authors.initials: L
authors.lastname: Cansolino
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Clerici
authors.forename: Elisa
authors.initials: E
authors.lastname: Viola
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Donzello
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Ricciardi
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054833:Isoindoles; D009369:Neoplasms / Q000532:radiotherapy*; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001896:Boron Compounds; D056831:Coordination Complexes; D007211:Indoles; D054833:Isoindoles; D014867:Water; D015032:Zinc; C013647:phthalocyanine