Studies of Rhodium(II) Carboxylates as Potential Antitumor Agents

Interactions of Metal—Metal‐Bonded Antitumor Active Complexes with DNA Fragments and DNA

“…Studies of the biological activity of dirhodium complexes conducted in the 1970s support the conclusion that tetracarboxylate compounds Rh 2 (µ-O 2 CR) 4 (R ) Me, Et, Pr) exhibit significant in vivo antitumor activity against L1210 tumors, 10 Ehrlich ascites, 8,9,11,12 sarcoma 180, and P388 tumor lines. 4 Although the precise antitumor mechanism of dirhodium carboxylate compounds has not been elucidated, it is known that they bind to DNA 8,9,13-15 and inhibit DNA replication and protein synthesis [16][17][18] in a manner akin to cisplatin.…”

“…A perusal of the literature reveals that, unlike cisplatin, dirhodium compounds bind strongly to polyadenylic acids and adenine nucleos(t)sides. 8,9,[31][32][33] These DNA binding preferences are considered to be related to the fact that dirhodium compounds are wellknown to react via trans substitution of ax ligands located at opposite ends of the dimer (Chart 1, structure a). Axial interactions between adenine (via position N7; Chart 2, structure a) and the dirhodium core are stabilized by formation of hydrogen bonds between the purine exocyclic NH 2 (6) amino group and the carboxylate oxygen atom of the dirhodium unit, as evidenced by the X-ray structural studies of Rh 2 (µ-O 2 CCH 3 ) 4 (1-MeAdo) 2 33 ( Figure 3) and 34 By comparison, the absence of guanine (Chart 2, structure b) ax adducts, when the dirhodium unit is supported solely by carboxylate groups, is attributed to electrostatic repulsions between the purine site O6 and the carboxylate oxygen atoms.…”

“…7 The basic paddlewheel structure of these compounds, which consists of a metalmetal-bonded fragment with at least two bridging ligands (Chart 1), appears to defy most of the accepted guidelines for metal anticancer agents. The recognition of the anticancer activity of tetracarboxylate compounds spawned a number of investigations in the 1970s regarding plausible cellular targets, 8,9 but research in this area steadily declined, in part, because the compounds did not surpass the anticancer activity of cisplatin. The revival of this research field in our laboratories over the past decade has been directed towards elucidating the biological activity of metal-metal-bonded systems vis-à-vis interactions with DNA, which is the primary target of platinum anticancer agents.…”

“…8,9,15 Figure 15). These findings refute earlier claims that no reaction between dirhodium compounds and dsDNA occurs.…”

Microwave-Assisted Synthesis and Characterization of [Rh2(OAc)4(L)2] Paddlewheel Complexes: A Joint Experimental and Computational Study

“…In this regard, the rhodium acetate complex [Rh 2 (OAc) 4 ], I, has been recognized as (i) a valuable, stable, and easy-tohandle catalyst; and (ii) a linker in the synthesis of inorganic polymers and cages, II and III, respectively ( Figure 1) [9][10][11][12][13]. The number of reports involving I in the fields of biochemistry [14][15][16][17], catalysis [18][19][20], and bioorganometallic [21,22], inorganic [23][24][25][26], and organometallic chemistry [27][28][29] has been increased to an average of sixty papers per year in the last decade (according to SciFinder at 03-01-2017).…”