3.9.2.3. Category 3: Photo-excitation of Enediyne Metal Complexes via Ligand-to-Metal or Metal-to-Ligand Charge Transfer
Photodynamic therapy relies on the use of longer excitation wavelengths for the drugs to be used. This will ensure enhanced tissue penetration by near-infrared (IR) photons. Therefore, two possible approaches can be adopted to shift the excitation wavelength to a longer region (beyond λ > 600 nm) required for photo-BC. The first choice of design involves the synthesis of enediynes with extended π conjugation. However this is synthetically challenging and may suffer from solubility problems. The alternative strategy is the use of long-wavelength electronic transition with considerable absorptivity that can be achieved via metal-to-ligand charge transfer (MLCT) process within compounds where both the metal oxidation state and donor/acceptor redox potentials have been properly chosen.
This idea was utilized demonstrated with design of a novel vanadium (V) metalloenediyne compound A of a 4,5-bis(phenylethynyl) benzene 1,2-diol ligand by Zaleski et al. The metalloenediyne exhibited strong ligand-to-metal charge transfer (LMCT) transitions in the near-IR region because of low redox potentials of the high valent vanadium center and the easily oxidizable metal-binding motif. Differential Scanning Calorimetry (DSC) and resonance Raman spectroscopy showed that these LMCTs can be successfully used to photothermally activate the metalloenediyne toward BC. Thus, upon laser excitation at 785 or 1064 nm compound A in the solid state become photothermally activated toward BC to produce the insoluble polymeric material C. The compound was inert to BC upon electronic excitation in the UV spectral region (Scheme 90) suggesting the necessity of excitation at very long wave length.
Scheme 90. Photo-excitation of enediyne via ligand-to-metal charge transfer (LMCT).
Photo-BC can also be prompted by MLCT. Zaleski et al. have reported that photolysis of copper complexes of Cu(bpod)2 PF6 and/or Cu(bpod)2 (NO3)2 ( A ) (bpod = cis -1,8-bis(pyridine-3-oxy)oct-4-ene-2,6-diyne) yielded BC of bound ligands. In contrast, the uncomplexed ligand and Zn(bpod)2 (CH3COO)2 compound (E) were photochemically inert under the same conditions (Scheme 91). The observed BC of the compounds A has been ascribed because of MLCT. Moreover, the intermediates produced upon photolysis are capable of degrading both pUC19 plasmid DNA as well as a 25 base pair double-stranded oligonucleotide via C-4' hydrogen-atom abstraction in micromolar concentrations.
Scheme 91. Photo-excitation of enediyne via metal-to-ligand charge transfer (MLCT).
The above example depicted nicely how a metal ion can facilitate photo-BC (Scheme 91). An interesting variation whereby the photo-BC is completely shut down upon metal complexation is provided in the next example (Scheme 92). Thus, the parent benzene-fused enediyne A undergoes photo-BC upon irradiation to produce the cycloaromatized product C via the diradical B . However, the ruthenium complex of A (D) did not produce any cyclized product upon similar photo-irradiation. This fact thus, highlights the importance of the electronic effect in controlling the BC kinetics (Scheme 92). The reluctance of compound D to undergo cycloaromatization (relative to A) is most likely due to decreased aromaticity in the incipient 1,4-diradical, which would be generated from D.
Scheme 92. Shut down of photo-BC of benzene-fused enediyne upon complexation with Ru- metal. |
