Porphyrins Conjugated with Peripheral Thiolato Gold(I) Complexes for Enhanced Photodynamic Therapy

Abstract

Porphyrins fused to imidazolium salts across two neighboring β-pyrrolic positions were used as N-heterocyclic carbene (NHC) precursors to anchor Au -Cl complexes at their periphery. Synthesis of several thiolato-Au complexes was then achieved by substituting chloride for thiolates. Photodynamic properties of these complexes were investigated: the data obtained show that the Au-S bonds could be cleaved upon irradiation. The proposed mechanism to explain the release of thiolate moiety involves the S atom oxidation by singlet oxygen generated in the course of irradiation. In view of photodynamic therapy (PDT) applications, these porphyrins fused to NHC-Au complexes were tested as photosensitizers to kill MCF-7 breast cancer cells. Results show the important role played by the ancillary ligands (chloride versus thiolates) on the photodynamic effect.

Peripherally Metalated Porphyrins with Applications in Catalysis, Molecular Electronics and Biomedicine

“…Although NHCs are best known as ligands for applications in catalysis, the stability of the NHC‐metal bond is an interesting property for biomedical applications to prevent the premature release of the metal ions and to improve the bioavailability of the metallodrugs . Free‐base porphyrins fused to NHC‐Au l ‐X complexes 66 – 68 (X=Cl or thiolates, see Figure ) were investigated for their photodynamic properties on MCF7 breast cancer cells . Compared to the corresponding imidazolium salt 8‐2H, the Au I porphyrin complex 66 is a better photosensitizer, because the efficiency of 7‐2H to generate 1 O 2 is about 60 % that of Au I complex 66 .…”

“…[82] Free-base porphyrins fused to NHC-Au l -X complexes 66-68 (X = Cl or thiolates, see Figure 7) were investigated for their photodynamic properties on MCF7b reast cancer cells. [83] Compared to the corresponding imidazolium salt 8-2H, the Au I porphyrin complex 66 is ab etter photosensitizer,b ecause the efficiency of 7-2H to generate 1 O 2 is about 60 %t hat of Au I complex 66.T his difference can be attributed to the heavy atom effect exertedb yt he peripheralA u I complex, as suggested by the lower fluorescenceq uantum yield and lifetime of the imidazolium salt 8-2H comparedt ot he Au I porphyrin complex 66.T he synthesis of thiolato-Au I complexes 67 and 68 was achieved by substituting the chloride of Au I complex 66 for thiolates. The Au I complex 68 is particularly interesting for targeted PDT because it containsamannose group susceptible of targeting MCF7 breastc ancerc ells, which are known to overexpressm annoser eceptors at their surface.…”

Molecular complexes and main-chain organometallic polymers based on Janus bis(carbenes) fused to metalloporphyrins

“…We have previously shown that porphyrins fused to imidazolium rings could be used as NHC precurors to anchor different metal ions such as palladium, 34,35 rhodium, 36 silver 37 and gold 38,39 at their periphery. Recently, we reported the synthesis of porphyrins containing two imidazolium rings fused to two opposite pyrrole units.…”

Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy

“…As demonstrated, the role of the mannose linked to Au I was of crucial importance in improving the global photodynamic effect. Based on the combination principle drug design strategies, Hu et al 120 combined a porphyrin skeleton, Pt(II)-based chemotherapeutic drug with a metal ion gallium (III) to improve the hydrophilicity and increase tumour accumulation. Due to its heavy atom effect, large pKa value, and localisation in the cytosol, the mixed-metal porphyrin Ga-4cisPtTPyP (64) exerted a high yield of singlet oxygen, more potent than the reference drug 4cisPtTPyP (51 b).…”