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Regioselective Synthesis and Photophysical and Electrochemical Studies of 20‐Substituted Cyanine Dye–Purpurinimide Conjugates: Incorporation of Ni II into the Conjugate Enhances its Tumor‐Uptake and Fluorescence‐Imaging Ability
Author(s) -
Ethirajan Manivannan,
Chen Ping,
Ohulchanskyy Tymish Y.,
Goswami Lalit N.,
Gupta Anurag,
Srivatsan Avinash,
Dobhal Mahabeer P.,
Missert Joseph R.,
Prasad Paras N.,
Kadish Karl M.,
Pandey Ravindra K.
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201203867
Subject(s) - cyanine , conjugate , chemistry , regioselectivity , fluorescence , photodynamic therapy , combinatorial chemistry , medicinal chemistry , photochemistry , stereochemistry , organic chemistry , catalysis , mathematical analysis , physics , mathematics , quantum mechanics
Abstract We report herein a simple and efficient approach to the synthesis of a variety of meso ‐substituted purpurinimides. The reaction of meso ‐ substituted purpurinimide with N ‐bromosuccinimide regioselectively introduced a bromo functionality at the 20‐position, which on further reaction with a variety of boronic acids under Suzuki reaction conditions yielded the corresponding meso ‐substituted analogues. Interestingly, the free base and the metalated analogues showed remarkable differences in photosensitizing efficacy (PDT) and tumor‐imaging ability. For example, the free‐base conjugate showed significant in vitro PDT efficacy, but limited tumor avidity in mice bearing tumors, whereas the corresponding Ni II derivative did not produce any cell kill, but showed excellent tumor‐imaging ability at a dose of 0.3 μmol kg −1 at 24, 48, and 72 h post‐injection. The limited PDT efficacy of the Ni II analogue could be due to its inability to produce singlet oxygen, a key cytotoxic agent required for cell kill in PDT. Based on electrochemical and spectroelectrochemical data in DMSO, the first one‐electron oxidation (0.52 V vs. SCE) and the first one‐electron reduction (−0.57–0.67 V vs. SCE) of both the free base and the corresponding Ni II conjugates are centered on the cyanine dye, whereas the second one‐electron reduction (−0.81 V vs. SCE) of the two conjugates is assigned to the purpurinimide part of the molecule. Reduction of the cyanine dye unit is facile and occurs prior to reduction of the purpurinimide group, which suggests that the cyanine dye unit as an oxidant could be the driving force for quenching of the excited triplet state of the molecules. An interaction between the cyanine dye and the purpurinimide group is clearly observed in the free‐base conjugate, which compares with a negligible interaction between the two functional groups in the Ni II conjugate. As a result, the larger HOMO–LUMO gap of the free‐base conjugate and the corresponding smaller quenching constant is a reason to decrease the intramolecular quenching process and increase the production of singlet oxygen to some degree.