M.C. McCormick et al. / Polyhedron 103 (2016) 28–34
29
Systems, area = 0.07 cm2), the reference electrode was Ag/AgCl
(Bioanalytical Systems, satd. NaCl) and the counter electrode was
a
platinum wire. The potential of the Ag/AgCl electrode is
+0.197 V vs. SHE. Pt(IV) complexes were dissolved in water to pre-
pare 1 mM solutions with 0.1 M sodium acetate (for 1) or potas-
sium chloride (for
2 and 3) as the supporting electrolyte.
Solutions were degassed with Ar for 5–10 min before experimenta-
tion, and each voltammogram was collected under a blanket of Ar.
The Pt and GC electrodes were polished for at least 2 min between
trials with 0.05-lm c-alumina (Buehler) slurry on a polishing cloth
(Buehler Microfiber), rinsed clean with DI water and dried with a
fiberless cleaning cloth. In cases where the electrode was pre-
cleaned or pre-activated by a multiple-scan experiment the elec-
trode was not polished before each scan; rather, the potentiostat
was switched off and the solution was stirred under Ar. Scan rates
ranging from 0.02 to 1.5 V sÀ1 were used. Peak potentials were
either located by fitting a Lorentzian to ꢀ20 data points close to
the maximum current or obtained from the CHI 620E software
package (CH Instruments).
Scheme 1. Two-electron reduction with subsequent ligand loss follows a stepwise
mechanism for compounds 1–3 as determined in Ref. [2].
Investigations seeking to establish relationships between struc-
ture and activity of these clinically important compounds need to
be based on an accurate and reliable determination of a relevant
fundamental parameter, in this case the standard reduction poten-
tial E°. Because of the irreversibility of the electrode reaction, many
researchers have chosen to use the cathodic peak potential, Epc, as a
substitute for E° in evaluating the efficacy of Pt(IV) prodrugs
[6,15,16,18–20,23]. Epc is a valid approximation of E° only in the
case of nearly ideal, reversible redox reactions, where the separa-
tion between Epc and Epa is ca. 60/n mV and Epc is more negative
than E° by only ca. 30/n mV [1]. In assessing the relative ease of
reduction of various Pt(IV) prodrugs, researchers have reported
Epc values measured under comparable, yet arbitrarily established,
experimental conditions. The underlying assumption is that poten-
tial differences between Epc and E° are identical in all circum-
3. Results and discussion
Table 1 summarizes the cathodic peak potential, Epc, associated
with the two-electron reduction of 1–3 determined by us and other
investigators under various experimental conditions. Compared to
values reported earlier using a GC electrode, potentials obtained
with a Pt electrode are much more positive. The differences range
from 260 to 630 mV. Namely, the literature results recorded at GC
electrodes in KCl electrolyte are found to be shifted by 534 mV for
1 (entry 8), 263 mV for 2 (entry 13), and 630 mV for 3 (entry 16)
relative to those recorded at Pt. Moreover, the range of Epc values
reported at GC for a given compound under comparable experi-
mental conditions is quite large (ca. 120–240 mV) compared to
that at Pt (ca. 10 mV). Although it is not unexpected that peak
potentials may change as different electrode materials are
employed, the magnitude of the variance is surprisingly large
and represents an inconsistency that has not been satisfactorily
explained to date.
stances and cancel to generate
a qualitatively meaningful
correlation. However, the complicated mechanistic and thermody-
namic issues discussed above raise serious concerns about the
validity of such a simplified approximation, as highlighted in our
recent study [2].
During the course of our work we found that linear sweep and
cyclic voltammograms of selected Pt(IV) prodrugs showed irrepro-
ducible peak potentials that varied greatly with experimental con-
ditions and produced estimates of E° that were grossly inconsistent
with quantum chemically calculated values. Subsequently, we
have identified glassy carbon (GC) electrodes to be the source of
these inconsistencies and have examined the voltammetric
response of Pt(IV) systems in greater detail at GC and Pt electrodes
to better understand the extent and nature of the artifactual shifts
in peak potential. The goal of this work is to identify the source of
the erratic behavior and to provide a basis for interpreting previous
work obtained at GC electrodes in a conceptually more satisfying
manner. In addition, we report a simple experimental procedure
that allows more consistent and reliable data to be obtained at
glassy carbon electrodes.
To better understand these discrepancies, we conducted exper-
iments under conditions identical to those reported in the litera-
ture and found that Epc for compound 1 in KCl occurred at a
more negative value than at Pt (À0.450 V, entry 3). Upon changing
Table 1
Cathodic peak potentials at 0.1 V sÀ1 from this and previously published work for
compounds 1–3 at platinum and glassy carbon working electrodes. Epc values from
this work represent average values obtained from at least 3 trials.
Entry
Compound
Refs.
Electrode
Electrolyte
Epc (V)d
a
a
a
a
a
a
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
1
2
2
2
2
3
3
3
3
Pt
Pt
KCl
À0.158
À0.155
À0.450
À0.511
À0.447
À0.555
À0.635
À0.689
À0.565
0.083
NaOAc
KCl
GC
GC
GC
GC
GC
GC
GC
Pt
2. Experimental
PBSb
KCl + NaCl
KCl + NaCl
2.1. Synthesis of complexes
[21]
[13]
KCl
c
Platinum prodrugs 1–3 were generously provided by Professor
Stephen J. Lippard (Massachusetts Institute of Technology, Cam-
bridge, MA). The general procedures for the synthesis of these pro-
drugs have been reported previously elsewhere [13,20].
9
[22]
KCl
KCl
a
10
11
12
13
14
15
16
17
a
a
Pt
NaOAc
KCl
0.090
0.091
GC
GC
Pt
GC
GC
GC
[4]
PBSb/KCl
KCl
À0.173
a
0.370
2.2. Electrochemistry
a
KCl
KCl
KCl
À0.122
À0.260
À0.204
[21]
[22]
Cyclic voltammetry experiments of all Pt(IV) prodrugs were
conducted in a three-electrode cell and recorded at room temper-
ature with an EG&G PAR 273A or a CH Instruments 620E potentio-
stat. The working electrode was a platinum disk (Bioanalytical
Systems, area = 0.02 cm2) or a glassy carbon disk (Bioanalytical
a
b
c
This work.
Phosphate buffered saline solution.
Electrolyte was not specified in Ref. [13].
V vs. Ag/AgCl.
d