Photoactivated in Vitro Anticancer Activity of Rhenium(I) Tricarbonyl Complexes Bearing Water-Soluble Phosphines

Abstract

Fifteen water-soluble rhenium compounds of the general formula [Re(CO)(NN)(PR)], where NN is a diimine ligand and PR is 1,3,5-triaza-7-phosphaadamantane (PTA), tris(hydroxymethyl)phosphine (THP), or 1,4-diacetyl-1,3,7-triaza-5-phosphabicylco[3.3.1]nonane (DAPTA), were synthesized and characterized by multinuclear NMR spectroscopy, IR spectroscopy, and X-ray crystallography. The complexes bearing the THP and DAPTA ligands exhibit triplet-based luminescence in air-equilibrated aqueous solutions with quantum yields ranging from 3.4 to 11.5%. Furthermore, the THP and DAPTA complexes undergo photosubstitution of a CO ligand upon irradiation with 365 nm light with quantum yields ranging from 1.1 to 5.5% and sensitize the formation of O with quantum yields as high as 70%. In contrast, all of the complexes bearing the PTA ligand are nonemissive and do not undergo photosubstitution upon irradiation with 365 nm light. These compounds were evaluated as photoactivated anticancer agents in human cervical (HeLa), ovarian (A2780), and cisplatin-resistant ovarian (A2780CP70) cancer cell lines. All of the complexes bearing THP and DAPTA exhibited a cytotoxic response upon irradiation with minimal toxicity in the absence of light. Notably, the complex with DAPTA and 1,10-phenanthroline gave rise to an IC value of 6 μM in HeLa cells upon irradiation, rendering it the most phototoxic compound in this library. The nature of the photoinduced cytotoxicity of this compound was explored in further detail. These data indicate that the phototoxic response may result from the release of both CO and the rhenium-containing photoproduct, as well as the production of O.

A Rare Type of Rhenium(I) Diimine Complexes with Unsupported Coordinated Phosphine Oxide Ligands: Synthesis, Structural Characterization, Photophysical and Theoretical Study

“…General Comments: [(Neocuproine)Re(CO) 3 (Cl)] ( 2ReCl ), [(Neocuproine)Re(CO) 3 (NCMe)]OTf ( 2ReNCMe ) and [(Phenantroline)Re(CO) 3 (NCMe)]OTf were synthesized according to the literature protocols , . Other reagents and solvents were used as received.…”

New Findings in Metal Complexes with Antiproliferative Activity Containing 1,3,5‐Triaza‐7‐phosphaadamantane (PTA) and Derivative Ligands

“…[32] Scheme 4. It is important to point out that Re-THP and Re-DAPTA compounds display triplet-based luminescence in air-equilibrated aqueous solutions (Φ = from 3.4 to 11.5 %), photo substitute one CO ligand (365 nm light; Φ = from 1.1 to 5.5 %) and sensitize the formation of 1 O 2 (Φ = up 70 %).…”

A Rhenium Isonitrile Complex Induces Unfolded Protein Response‐Mediated Apoptosis in Cancer Cells

“…[6][7][8][9][10][11] In this context,our group has been exploringthe anticancera ctivity of polypyridyl rhenium(I) tricarbonyl complexes. [12][13][14][15] Certain members of this class of compounds exhibit potent cytotoxic activity,w hich can be leveragedf or their use as anticancer agents. [16][17][18][19][20][21][22][23] Here, we describe our investigation of an ew rhenium(I) tricarbonyl complexb earing ac helating polypyridyl liganda nd an axial isonitrile ligand as ap otent anticancer agent.O ur efforts to understand the mechanismo f actiono ft his tricarbonyl rhenium isonitrile polypyridyl (TRIP) complex ( Figure 1) have revealed that it is an effective ER stress-inducing agent with significant antiproliferativeactivity.…”