Conditions Favoring the Formation of Monomeric Pt^III Derivatives in the Electrochemical Oxidation of trans‐[Pt^II{(p‐BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)]

Abstract

Characterization of the anticancer active compound trans‐[PtII{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)] is described along with identification of electrochemical conditions that favor formation of a monomeric one‐electron‐oxidized PtIII derivative. The square‐planar organoamidoplatinum(II) compound was synthesized through a carbon dioxide elimination reaction. Structural characterization by using single‐crystal X‐Ray diffraction reveals a trans configuration with respect to donor atoms of like charges. As PtIII intermediates have been implicated in the reactions of platinum anticancer agents, electrochemical conditions favoring the formation of one‐electron‐oxidized species were sought. Transient cyclic voltammetry at fast scan rates or steady‐state rotating disc and microelectrode techniques in a range of molecular solvents and an ionic liquid confirm the existence of a well‐defined, chemically and electrochemically reversible one‐electron oxidation process that, under suitable conditions, generates a PtIII complex, which is proposed to be monomeric [PtIII{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)]+. Electron paramagnetic resonance spectra obtained from highly non‐coordinating dichloromethane/([Bu4N][B(C6F5)4]) solutions, frozen to liquid nitrogen temperature immediately after bulk electrolysis in a glove box, support the PtIII assignment rather than formation of a PtII cation radical. However, the voltammetric behavior is highly dependent on the timescale of the experiments, temperature, concentration of trans‐[PtII{(p‐BrC6F4)NCH2CH2NEt2}‐ Cl(py)], and the solvent/electrolyte. In the low‐polarity solvent CH2Cl2 containing the very weakly coordinating electrolyte [Bu4N][B(C6F5)4], a well‐defined reversible one‐electron oxidation process is observed on relatively long timescales, which is consistent with the stabilization of the cationic platinum(III) complex in non‐coordinating media. Bulk electrolysis of low concentrations of [Pt{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)] favors the formation of monomeric [PtIII{(p‐BrC6F4)NCH2CH2NEt2}Cl(py)]+. Simulations allow the reversible potential of the PtII/PtIII process and the diffusion coefficient of [PtIII{(p‐BrC6F4)‐ NCH2CH2NEt2}Cl(py)]+ to be calculated. Reversible electrochemical behavior, giving rise to monomeric platinum(III) derivatives, is rare in the field of platinum chemistry.

Electron Delocalization in Spectroelectrochemically and Computationally Characterized [Pt{(p-BrC6F4)NCH═C(Cl)NEt2}Cl(py)]+ Formed by Electrochemical Oxidation of [PtII{(p-BrC6F4)NCH═C(Cl)NEt2}Cl(py)]

“…Cyclic voltammograms obtained after the bulk electrolysis using multiple cycling of the potential (Figure f) display the theoretically expected small decrease in the magnitude of the current with each cycle, but no new processes emerge. All of these data confirm that 1Cl + remains fully stable even under long-time-scale bulk electrolysis conditions, unlike 1 + and 2 + generated via bulk electrolysis of 1 and 2 . , After many attempts, single crystals of 1Cl + could not be obtained from the oxidized solution obtained after the bulk electrolysis, even at low temperatures (see the Experimental Section).…”

“…Clearly, the oxidation of 1Cl to 1Cl + is reversible under both steady-state microelectrode and transient macrodisk electrode conditions in CH 2 Cl 2 (0.10 M [Bu 4 N]­[PF 6 ]). Thus, the formal Pt II/III process can be described by the electrochemical ( E ) step (eq ), with no evidence for a chemical ( C ) step (eq ) following the electron transfer process, as reported for related complexes. ,, The oxidation of 1Cl exhibits the same ideal characteristics found for the known reversible one-electron oxidation of Fc to Fc + under both steady-state and transient voltammetric conditions …”

“…Under transient cyclic voltammetric conditions at a macrodisk Pt electrode with a slow scan rate (20 mV s –1 ), a reversible one-electron 1Cl/1Cl + process also is obtained, as shown in Figure b. In cyclic voltammograms of 1 and 2 obtained at scan rates <100 mV s –1 , a small oxidative shoulder with a reductive counterpart is evident after the initial one-electron oxidation process. , In contrast, there is no follow-up chemical process evident after the oxidation of 1Cl even at a very slow scan rate, which implies that 1Cl + is significantly more stable than 1 + or 2 + .…”

“…The stability of the four-coordinated Pt III state can also be enhanced by shielding both axial positions to inhibit oxidative addition reactions . Similarly, axial position protection achieved by agostic interactions contributes to the stability of [Pt­{( p -BrC 6 F 4 )­NCH 2 CH 2 NEt 2 }­Cl­(py)] + formed by the electrochemical oxidation of [Pt­{( p -BrC 6 F 4 )­NCH 2 CH 2 NEt 2 }­Cl­(py)]. , …”

“…The synthesis and characterization of class 2 Pt II anticancer agents [Pt­{( p -YC 6 F 4 )­N­(R)­CH 2 CH 2 NR′2}­X­(py)] (Y = H, F, Br; R = polyfluoroaryl; R′ = Et, Me; and X = Cl, Br, I) have been reported in several studies from Monash University. ,− The electrochemical oxidation of some of these materials has shed light upon conditions favoring the formation of formally monomeric Pt III derivatives. , Electrochemically reversible and close to chemically reversible one-electron oxidation processes have been reported for the anticancer compounds [Pt II {( p -BrC 6 F 4 )­NCH 2 CH 2 NEt 2 }­Cl­(py)], 1 , and [Pt II {( p -HC 6 F 4 )­NCH 2 CH 2 NEt 2 }­Cl­(py)], 2 , under short-time-scale (fast-scan-rate) cyclic voltammetric conditions at 23 °C in dichloromethane. However, instability of these formal Pt III products is evident under both slow-scan-rate cyclic voltammetric and longer-time-scale bulk electrolysis conditions.…”