Syntheses, structures, and electrochemical studies of N,N′-bis(alkylthiocarbamate)butane-2,3-diimine Cu(II) complexes as pendent alkoxy derivatives of Cu(ATSM)

Article abstract of DOI:10.1016/j.ica.2017.02.003

A series of N₂S₂-Cu(II) complexes based on N,N′-bis(alkylthiocarbamate)butane-2,3-diimine ligands have been synthesized and characterized by spectroscopic, electrochemical, and single crystal X-ray diffraction methods. This class of ligands contains a conjugated N₂S₂chelate framework with a non-coordinating, terminal alkoxy (–OR) group. Ligands and Cu(II) complexes were investigated for R = Me, Et,ⁿPr,ⁱPr, and octyl. Additionally, N,N′-bis(ethylthiocarbamate)hexane-3,4-diimine and its Cu(II) complex were analyzed. Single crystal X-ray diffraction studies on all six Cu(II) complexes confirm a square planar Cu(II) environment with no significant changes in the core structure as a function of R. Spectroscopic studies are consistent with a similar electronic environment in all complexes. However, electrochemical investigations reveal significant shifts in the Cu^II/Iand Cu^III/IIreduction potentials throughout the series. The complexes are analogues of the well-known bis(thiosemicarbazone) Cu(II) which contain a similar donor core with terminal, non-coordinating amines. Substitution of the terminal amines of bis(thiosemicarbazones) with the alkoxy groups of N,N′-bis(alkylthiocarbamate)butane-2,3-diimines allows tuning of redox potentials with minimal changes in the physical and electronic structure.

Full text of DOI:10.1016/j.ica.2017.02.003

Inorganica Chimica Acta 461 (2017) 45–51
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Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Research paper
Syntheses, structures, and electrochemical studies of N,N0-bis
(alkylthiocarbamate)butane-2,3-diimine Cu(II) complexes as pendent
alkoxy derivatives of Cu(ATSM)
⇑
Nicholas S. Vishnosky, Mark S. Mashuta, Robert M. Buchanan, Craig A. Grapperhaus
Department of Chemistry, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, United States
a r t i c l e i n f o
a b s t r a c t
A series of N2S2-Cu(II) complexes based on N,N0-bis(alkylthiocarbamate)butane-2,3-diimine ligands have
been synthesized and characterized by spectroscopic, electrochemical, and single crystal X-ray diffraction
methods. This class of ligands contains a conjugated N2S2 chelate framework with a non-coordinating,
Article history:
Received 2 February 2017
Accepted 3 February 2017
i
terminal alkoxy (–OR) group. Ligands and Cu(II) complexes were investigated for R = Me, Et, nPr, Pr,
and octyl. Additionally, N,N0-bis(ethylthiocarbamate)hexane-3,4-diimine and its Cu(II) complex were
analyzed. Single crystal X-ray diffraction studies on all six Cu(II) complexes confirm a square planar Cu
(II) environment with no significant changes in the core structure as a function of R. Spectroscopic studies
are consistent with a similar electronic environment in all complexes. However, electrochemical investi-
gations reveal significant shifts in the CuII/I and CuIII/II reduction potentials throughout the series. The
complexes are analogues of the well-known bis(thiosemicarbazone) Cu(II) which contain a similar donor
core with terminal, non-coordinating amines. Substitution of the terminal amines of bis(thiosemicar-
bazones) with the alkoxy groups of N,N0-bis(alkylthiocarbamate)butane-2,3-diimines allows tuning of
redox potentials with minimal changes in the physical and electronic structure.
Ó 2017 Elsevier B.V. All rights reserved.
1. Introduction
position has largely focused on other amine derivatives to investi-
gate the impact on selectivity and/or reduction potential. In gen-
The biological applications of the copper complex Cu(ATSM)
(ATSM = diacetyl-bis(4-methylthiosemicarbazonato) as a diagnos-
tic and therapeutic agent have been extensively studied. The Cu
(II) ion sits in a conjugated dianionic N2S2 framework with termi-
nal –NHMe functional groups that do not participate in metal-
ligand binding, Scheme 1. Cu(ATSM) has been evaluated as a
64Cu and 62Cu radiopharmaceutical for selective imaging of
hypoxia [1–5]. The neutral, planar Cu(ATSM) is proposed to diffuse
through cell membranes with no net uptake under normoxic con-
ditions. However, under the low oxygen conditions of hypoxia Cu
(ATSM) is reduced preventing it from exiting the cell. More
recently, Cu(ATSM) has been evaluated for the treatment of cancer
[6] and neurodegenerative diseases [7–10]. Phase I clinical trials as
a therapeutic for amyotrophic lateral sclerosis/motor neuron dis-
ease (ALS/MND) are currently underway [11].
eral, chain extension has a small effect on the CuII/I potential
[12,13], although modification with aromatic rings can lead to sta-
bilization of Cu(I) by as much as +240 mV [14]. Que and co-workers
recently reported symmetric and asymmetric R1 derivatives with
the –NHMe groups replaced with –NHCH2CF3 with stabilization
of Cu(I) by ꢀ70 mV per –NHCH2CF3. Interestingly, these complexes
allow for hypoxia imaging by 19F MRI, thus avoiding the need for
64Cu [15]. Variation of the R2 backbone methyl groups with hydro-
gen or phenyl substituents also stabilize Cu(I), with the latter
showing a larger effect of ꢀ240 mV [12,14]. The effect of R2 group
substitution for a wide variety of functional groups was evaluated
using experimentally benchmarked density functional theory cal-
culations of Cu(II/I) reduction potentials. A Hammett analysis of
the theoretical Cu(II/I) potentials is consistent with an inductive
effect with Cu(I) stabilized by electron-withdrawing substituents
[22].
The biological importance of Cu(ATSM) has led to the synthesis
and characterization of a large number of related copper bis
(thiosemicarbazonato) complexes with symmetric and asymmetric
variation at the R1 and R2 positions [12–21]. Substitution at the R1
The numerous derivatives of Cu(ATSM) reported to date have by
and large maintained an N2S2 donor core with terminal amine
based R1 groups. Our research highlights a modification to the
ligand framework by incorporation of alkoxy groups at the
terminal R1 position. As outlined in Scheme 1, a series of six ligands
and their Cu(II) derivatives have been synthesized and fully
⇑
Corresponding author.
E-mail address: grapperhaus@louisville.edu (C.A. Grapperhaus).
http://dx.doi.org/10.1016/j.ica.2017.02.003
0020-1693/Ó 2017 Elsevier B.V. All rights reserved.

46
N.S. Vishnosky et al. / Inorganica Chimica Acta 461 (2017) 45–51
2,3-butanedione (0.66 mL, 0.0075 mol) in ethanol (50 mL).
Yield = 0.95 g (40%). 1H NMR, (CDCl3, 400 MHz) d 0.99 (t, 6H,
J = 7.28) 1.84 (quint, 4H, J = 6.24 Hz) 2.13 (s, 6H) 4.55 (t, 4H,
J = 6.22 Hz) 9.15 (s, 2H). 13C{1H} NMR, (CDCl3, 100 MHz) d 9.78,
10.3, 21.9, 29.7, 187.6. IR cmꢁ1. 3234 (w) and 1497(s) (NH) 1402
(m) (CH) 1334 (m) and 1207 (s) (CN) 1135 (s) (CO) 1052 (s) (CS).
2.5. N,N0-bis(isopropylthiocarbamate)butane-2,3-diimine, Hi2PTCB (4)
Compound
4
was prepared as described for
1
from
hydrazinecarbothioic acid O-isopropyl ester (5.1 g, 0.038 mol)
and 2,3-butanedione (1.7 mL, 0.019 mol) in ethanol (50 mL).
Yield = 1.4 g (23%). 1H NMR, (CDCl3, 400 MHz) d 1.41 (br, 12H)
2.12 (s, 6H) 5.63 (br, 2H) 9.10 (s, 2H). 13C{1H} NMR, (CDCl3,
100 MHz) d 10.3, 21.9. IR cmꢁ1. 3234 (w) and 1497(s) (NH) 1402
(m) (CH) 1334 (m) and 1207 (s) (CN) 1135 (s) (CO) 1052 (s) (CS).
2.6. N,N0-bis(octylthiocarbamate)butane-2,3-diimine, H2OTCB (5)
Compound
5
was prepared as described for
1
from
Scheme 1. Syntheses of complexes 7–12.
hydrazinecarbothioic acid O-octyl ester (2.72 g, 0.013 mol) and
2,3-butanedione (0.58 mL, 0.0067 mol) in ethanol (50 mL).
Yield = 1.77 g (58%). 1H NMR, (CDCl3, 400 MHz) d 0.87 (br, 6H)
1.28 (m, 16H) 1.43 (br, 4H) 1.81 (br, 4H) 2.13 (s, 6H) 4.59 (br,
4H) 9.12 (s, 2H). 13C{1H} NMR, (CDCl3, 100 MHz) d 14.1, 22.6,
25.8, 28.4, 29.1, 31.7. IR cmꢁ1: 3230 (w) and 1497 (vs) (NH)
2950–2850 (m) and 1404 (s) (CH) 1326 (s) and 1206 (vs) (CN)
1136 (s) (CO) 1056 (s) (CS).
characterized. One compound was previously synthesized and
characterized by UV–visible spectroscopy [23]. As detailed below,
this results in a substantial shift in the Cu(II/I) reduction potential
relative to Cu(ATSM).
2. Experimental section
2.7. N,N0-bis(ethylthiocarbamate)hexane-3,4-diimine, H2ETCH (6)
2.1. Materials and methods
Compound
6
was prepared as described for
1
from
All reagents and solvents were purchased from commercial
sources and used as received unless otherwise indicated. Reactions
were conducted open to air and under ambient conditions unless
otherwise noted. Xanthates [24] and hydrazinecarbothioc acid O-
alkyl esters [25] were synthesized according to literature methods.
hydrazinecarbothioic acid O-ethyl ester (1.53 g, 0.013 mol) and
3,4-hexanedione (0.77 mL, 0.0065 mol) in ethanol (50 mL).
Yield = 1.2 g (60%). 1H NMR, (400 MHz, CDCl3) d 1.08 (br, 6H)
1.41 (br, 6H) 2.63 (br, 4H) 4.63 (br, 4H) 9.23 (br, 2H). 13C{1H}
NMR, (100 MHz, CDCl3) d 10.49, 14.02, 17.01, 68.87, 152.27,
187.47. IR cmꢁ1: 3235 (w) and 1498 (m) (NH) 1433 (w) (CH)
1314 (m) and 1206 (s) (CN) 1152 (m) (CO) 1059 (s) (CS).
2.2. N,N0-Bis(methylthiocarbamate)butane-2,3-diimine, H2MTCB (1)
The hydrazinecarbothioic acid O-methyl ester (3.2 g, 0.030 mol)
was dissolved in ethanol (50 mL). To this solution 2,3-butanedione
(1.3 mL, 0.015 mol) was added via syringe with stirring. A catalytic
amount (5 drops) of concentrated sulfuric acid was added resulting
in a white precipitate. The suspension was stirred for 16 h. The
white precipitate was isolated by filtration and washed with etha-
nol and ether. Yield = 3.6 g (93%). 1H NMR, (C2D6SO, 400 MHz) d
2.11 (s, 6H) 4.03 (s, 6H) 11.46 (s, 1H) 11.77 (s, 1H). 13C{1H} NMR,
(CDCl3, 100 MHz) d 12.3, 58.5, 117.8, 188.0. IR cmꢁ1: 3240 (w)
and 1503 (m) (NH) 1419 (m) (CH) 1341 (m) and 1222 (s) (CN)
1137 (s) (CO) 1060 (s) (CS).
2.8. Cu(MTCB) (7)
Compound 1 (0.273 g, 0.00129 mol) was suspended in metha-
nol (25 mL). To this suspension copper (II) acetate monohydrate
(0.285 g, 0.00149 mol) was added with stirring giving a red-brown
precipitate. The suspension was heated to reflux for 4 h with stir-
ring. The suspension was allowed to cool to room temperatures
and then filtered and the solid was washed with methanol and
ether. Yield = 0.216 g (52%). X-ray quality crystals were obtained
by slow evaporation of a dichloromethane solution of 7 layered
with ethanol. IR cmꢁ1: 1471 (s) and 1398 (m) (CH) 1241 (vs) and
1218 (vs) (CN) 1091 (w) (CO) 948 (w) (CS) 848 (w) (CuS) 771 (w)
(CuN). Elemental analysis calc. for C8H12S2O2N4Cu: C, 29.67, H,
3.73, N, 17.30. Found C, 28.49, H, 3.58, N, 15.97. Mass spectrum
calc. for C8H12S2O2N4Cu: 322.9698. Found: 322.9775.
2.3. N,N0-bis(ethylthiocarbamate)butane-2,3-diimine, H2ETCB (2)
Compound 2 was prepared using the same protocol as for 1.
Addition of 2,3-butanedione (2.3 mL, 0.027 mol) to hydrazinecar-
bothioic acid O-ethyl ester (6.4 g, 0.053 mol) in ethanol (50 mL)
yielded 2 as a white solid. Yield = 7.74 g (98%). 1H NMR, (C2D6NO,
400 MHz) d 1.51 (br, 6H) 2.46 (br, 4H) 4.74 (s, 6H) 11.51 (s, 1H)
11.92 (s, 1H). IR cmꢁ1: 3241 (w) and 1498 (s) (NH) 1403 (m)
(CH) 1317 (m) and 1211 (s) (CN) 1135 (m) (CO) 1049 (m) (CS).
2.9. Cu(ETCB) (8)
Compound 8 was prepared using the methods described for 7
from 2 (0.309 g, 0.00129 mol) and copper (II) acetate monohydrate
(0.285 g, 0.00149 mol) in methanol (25 mL). Complex 8 was iso-
lated as a red-brown solid. Yield = 0.237 g (52%). X-ray quality
crystals were obtained by using the technique described for 7. IR
cmꢁ1: 1413 (s) (CH) 1216 (s) (CN) 1020 (m) (CO) 867 (w)
(CS) 792 (w) (CuS) 673 (w) (CuN). Elemental analysis calc. for
2.4. N,N0-bis(n-propylthiocarbamate)butane-2,3-diimine, H2PTCB (3)
Compound
3
was prepared as described for
1
from
hydrazinecarbothioic acid O-propyl ester (2.1 g, 0.015 mol) and
C10H16S2O2N4Cu: C, 34.13, H, 4.58, N, 15.92, O, 9.09, S, 18.22. Found

N.S. Vishnosky et al. / Inorganica Chimica Acta 461 (2017) 45–51
47
C, 34.08, H, 4.40, N, 15.46, O, 9.18, S, 18.22. Mass spectrum calc. for
10H16S2O2N4Cu: 351.0011. Found: 351.0086.
on a Nicolet 360 FT-IR with a smart iTR attachment. NMR spectra
were obtained on Varian 400-M Hz spectrometer at 25 °C.
C
2.10. Cu(PTCB) (9)
2.15. Electrochemical measurements
Compound 9 was prepared using the methods described for 7
from 3 (0.408 g, 0.00129 mol) and copper (II) acetate monohydrate
(0.285 g, 0.00149 mol) in methanol (25 mL). Complex 9 was iso-
lated as a red-brown solid. Yield = 0.322 g (68%). X-ray quality
crystals were obtained by using the technique described for 7. IR
cmꢁ1: 1467 (w) and 1423 (s) (CH) 1236 (s) (CN) 1093 (w) (CO)
956 (m) (CS) 844 (w) (CuS) 632 (w) (CuN). Elemental analysis calc.
for C12H20S2O2N4Cu: C, 37.93, H, 5.31, N, 14.74, O, 8.42, S, 16.88.
Found, C, 37.99, H, 5.10, N, 14.67, O, 8.32, S, 16.75. Mass spectrum
calc. for C12H20S2O2N4Cu: 379.0324. Found: 379.0417.
Electrochemical data were collected using a Gamry Interface
1000E Potentiostat/Galvanostat/ZRA. Complexes were dissolved
in dichloromethane (ꢀ2 mM) under air free conditions in a stan-
dard three electrode cell with 0.1 M tetrabutylammonium hexaflu-
orophosphate as supporting electrolyte. Glassy carbon was used as
the working electrode with a platinum wire counter electrode and
a silver wire pseudo reference electrode. A small quantity of fer-
rocene was added as internal standard and all potentials are refer-
enced versus ferrocenium/ferrocene (Fc+/Fc).
2.16. Crystallographic methods
2.11. Cu(iPTCB) (10)
Single crystal X-ray diffraction studies were conducted on com-
plexes 7–12. Details of the data collection and refinement are dis-
played in Table S1 with full experimental details provided in the
Supplementary Information. Crystals 7 and 8 were mounted on a
CryoLoop and 9–12 were mounted on a glass fiber for collection
of X-ray data on an Agilent Technologies/Oxford Diffraction Gemini
CCD diffractometer. The CrysAlisPro [26] CCD software package (v
Compound 10 was prepared using the methods described for 7
from 4 (0.408, 0.00129 mol) and copper (II) acetate monohydrate
(0.285 g, 0.00149 mol) in methanol (25 mL). Complex 10 was iso-
lated as a red-brown solid. Yield = 0.291 g (60%). %). X-ray quality
crystals were obtained by using the technique described for 7. IR
cmꢁ1: 1427 (s) (CH) 1213 (vs) (CN) 1103 (vs) (CO) 910 (m) (CS)
831 (w) (CuS) 671 (w) (CuN). Elemental analysis C12H20S2O2N4Cu:
C, 37.93, H, 5.31, N, 14.74, O, 8.42, S, 16.88. Found, C, 37.38, H, 5.16,
N, 14.39, O, 8.61, S, 17.10. Mass spectrum cal. For C12H20S2O2N4Cu:
379.0324. Found: 379.0401.
1.171.36.32) was used to acquire
x-scan exposures of data at 100 K
using monochromated MoK radiation (0.71073 Å) from a sealed
a
tube. Frame data were processed using CrysAlisPro [26] RED to
determine final unit cell parameters to produce raw hkl data that
were then corrected for absorption using SCALE3 ABSPACK [27].
The structures were solved by Direct Methods using SHELX [28]
and refined by least squares methods on F2 using SHELXL-97
[28]. For each crystal, non-hydrogen atoms were refined anisotrop-
ically while hydrogen atoms were refined as described in the Sup-
plementary Information. For all unique reflections the final
anisotropic full matrix least-squares refinement on F2 for all vari-
ables converged with R1, wR2, GOF as listed in Table S1.
2.12. Cu(OTCB) (11)
Compound 11 was prepared using the methods described for 7
from 5 (0.589 g, 0.00129 mol) and copper (II) acetate monohydrate
(0.285 g, 0.00149 mol) in methanol (25 mL). Complex 11 was iso-
lated as a red-brown solid. Yield = 0.554 g (83%). X-ray quality
crystals were obtained by using the technique described for 7. IR
cmꢁ1: 2960–2852 (m) and 1423 (s) (CH) 1238 (vs) (CN) 1079 (w)
(CO) 946 (m) (CS) 846 (m) (CuS) 676 (w) (CuN). Elemental analysis
3. Results
C22H40S2O2N4Cu: C, 50.79, H, 7.75, N, 10.77, O, 6.15, S, 12.33.
Found, C, 50.49, H, 7.57, N, 10.65, O, 6.34, S, 12.59. Mass spectrum
calc. for C22H40S2O2N4Cu: 519.1889. Found: 519.1986.
3.1. Synthesis and characterization
A series of N2S2 N,N0-bis(alkylthiocarbamate)butane-2,3-dii-
mine ligands (1–5) with varying O-alkyl chain lengths and N,N0-
bis(methylthiocarbamate)hexane-3,4-diimine (6) have been pre-
pared and complexed with Cu(II) yielding the square planar com-
plexes 7–12, Scheme 1. The ligands were obtained in three steps
from inexpensive bulk commodity chemicals, Scheme 2. Using pre-
viously reported methods, xanthates were prepared from the
appropriate alcohol and carbon disulfide [24] and subsequently
condensed with hydrazine monohydrate to yield the hydrazinecar-
2.13. Cu(ETCH) (12)
Compound 12 was prepared using the methods described for 7
from 6 (0.408, 0.00129 mol) and copper (II) acetate monohydrate
(0.285 g, 0.00149 mol) in methanol (25 mL). Complex 12 was iso-
lated as a red-brown solid. Yield = 0.401 g (82%). X-ray quality
crystals were obtained by using the technique described for 7. IR
cmꢁ1: 1417 (s) (CH) 1221 (s) (CN) 1016 (s) (CO) 974 (w) (CS) 874
(m) (CuS) 630 (m) (CuN). Elemental analysis for C12H20S2O2N4Cu:
C, 37.93, H, 5.31, N, 14.74, O, 8.42, S, 16.88. Found, C, 37.71, H,
4.96, N, 14.43, O, 8.33, S, 16.95. Mass spectrum calc. for
C12H20S2O2N4Cu: 379.0324. Found: 379.0315.
2.14. Physical methods
Elemental analysis was performed by Midwest Micro lab (Indi-
anapolis, IN). The electronic spectra were collected as dichloro-
methane solution in 1 cm quartz cuvettes using an Agilent 8453
diode array spectrometer. Mass spectrometry (+ESI-MS) was per-
formed by the Regenerative Medicine Research Center at the West
China Hospital, Sichuan University, Chengdu, China. All EPR data
were collected on powder samples at room temperature using a
Bruker EMX X-band spectrometer. EPR spectra were simulated
using EasySpin. The infrared spectra were recorded as powders
Scheme 2. Syntheses of ligands 1–6.

48
N.S. Vishnosky et al. / Inorganica Chimica Acta 461 (2017) 45–51
bothioic acid O-alkyl esters [25]. Condensation of the ester with
butanedione (1–5) or hexanedione (6) yielded the desired ligand
in a reaction similar to H2ATSM synthesis [29]. Addition of copper
acetate monohydrate to suspensions of the ligands in methanol
yielded 7–12 as dark red powders in 52–83% yield.
the electronic spectrum. The spectrum of 7 is too broad to resolve
the axial signal, but the observed g-value of 2.061 is near the aver-
age g-values of the other complexes.
3.2. Crystallographic studies
The electronic spectra of 7–12 recorded in dichloromethane dis-
play a ligand to metal charge transfer band near 485 nm and two
more intense ligand to ligand charge transfer bands near 248 and
290 nm. The transition energies are largely insensitive to the iden-
tity of the O-alkyl group R1 or the backbone substituent R2, Table 1.
The infrared spectra of ligands 1–6 display an NAH stretch
between 3230 and 3241 cmꢁ1 that is lost upon metal complexa-
tion. The EPR spectra of 7–12 were recorded as powders at room
temperature. Complexes 8–12 display an axial spectrum with
g|| > g\ > 2 (Table 1) consistent with square planar Cu(II) and a sin-
X-ray quality diffraction crystals of 7–12 were obtained as
orange needles or plates upon slow evaporation of a dichloro-
methane solution of the complex layered with ethanol. Crystal data
and structure refinement details are listed in Table S1. All com-
plexes crystallize as discrete, square planar Cu(II) complexes with
no solvent molecules in the crystal lattice. An ORTEP representa-
tion of 7 is shown in Fig. 1 with selected bond distances and angles
provided in Table 2. The structures of 8–12 are highly similar to 7
with core structure bond distances and angles statistically indistin-
guishable from those in 7, see Supplementary Information. The fol-
lowing discussion of 7 is representative of the entire group of
complexes.
2
gle unpaired electron located in dx2-y . Simulated values for g|| and
g\ fall in the narrow ranges of 2.031–2.042 and 2.089–2.131,
respectively, consistent with the similarities observed for 8–12 in
Table 1
UV–visiblea, EPRb, and electrochemicalc data for N,N0-bis(alkylthiocarbamate)butane-2,3-diimine Cu(II) complexes 7–12 and selected Cu(ATSM) derivatives.
a
b
Complex
R1
R2
kmax (nm) (
e)
g||, g\ (gavg
)
CuIII/IIcE1/2 (mV) (ipc/ipa
)
CuII/Ic E1/2 (mV) (ipc/ipa
ꢁ857 (0.941)
)
Refs.
7
OMe
Me
246 (16,000)
290 (20,000)
486 (2680)
248 (16,300)
290 (22,700)
485 (2920)
248 (16,600)
291 (23,800)
484 (2930)
248 (16,500)
292 (23,600)
484 (3210)
248 (15,900)
291 (23,600)
485 (3100)
249 (18,300)
292 (25,000)
485 (3340)
261
(2.061)
585 (0.934)
This work
8
OEt
Me
Me
Me
Me
Et
2.131, 2.036
(2.068)
528 (0.933)
542 (0.964)
505 (0.867)
545 (0.929)
549 (0.934)
200
ꢁ879 (0.965)
ꢁ892 (0.997)
ꢁ904 (0.964)
ꢁ884 (0.867)
ꢁ874 (0.975)
ꢁ1110
This work
This work
This work
This work
This work
9
OnPr
OiPr
2.127, 2.034
(2.065)
10
11
12
13
14
15
2.089, 2.042
(2.058)
O-octyl
OEt
2.130, 2.034
(2.066)
2.124, 2.031
(2.062)
NHMe
NH2
Me
Me
Me
2.113, 2.029, 2.026
(2.056)
[12]a,c
[31]b
314
477
263
310
477
320
450
N/A
ꢁ180
ꢁ1110
[12]
[31]
NMe2
2.085, 2.033, 2.024
(2.047)
N/A
N/A
490
525
16
17
N(C4H8)
NPhMe
Me
H
321
368
515
566
323
381
N/A
N/A
N/A
N/A
ꢁ1050
[14]
[14]
(1.03)
ꢁ700
(0.99)
512
567
N/A
194
262
18
19
NHEt
NHMe
Me
H
N/A
N/A
N/A
N/A
ꢁ1120d
ꢁ950
[32]
[12]
324
495
20
NHMe
Et
194
267
N/A
190
ꢁ1100
[12]
316
483
a
b
c
Electronic spectra measured in CH2Cl2 (7–12), DMSO (13, 14, 19, 20), or DMF (15–17) solution.
Powder EPR spectra collected on solids at room temperature (7–12, 13, 15); gavg = 1/3[g|| + 2g].
Electrochemical potentials versus Fc+/Fc measured versus an internal standard in CH2Cl2 with 0.1 M nBu4NBF4 (7–12) or calculated from reported potentials versus Ag/
AgCl in DMSO with 0.1 M nBu4NBF4 (13, 14, 19, 20) or versus SCE in DMF with 0.1 M nBu4ClO4 (16, 17) using the following conversions: E1/2 = ꢁ0.52 for Fc+/Fc vs. Ag/AgCl in
DMSO; = E1/2 = ꢁ0.51 for Fc+/Fc vs. SCE in CH2Cl2 (7–13), DMSO (13, 14, 19, 20), or DMF (16, 17).
d
Reported as 10 mV more negative than 13.

N.S. Vishnosky et al. / Inorganica Chimica Acta 461 (2017) 45–51
49
Fig. 1. ORTEP [30] view (50% probability) of 7 showing atom labeling for all non-
hydrogen atoms in the asymmetric unit and symmetry generated (1 ꢁ x, ꢁy, 1/
2 ꢁ z) donor atoms.
Fig. 2. Representation of the conjugated
mate)butane-2,3-diimine ligand of 7 highlighting localization of the C=N bonds.
p
-network of the N,N0-bis(alkylthiocarba-
Table 2
Selected bond distances (Å) and bond angles (°) for 7 and 13 [33] as representative
examples
of
Cu(alkoxythiocarbamidates)
and
Cu(thiosemicarbazonates),
respectively.a
Bond distance
7
13
Cu–N1
Cu–S1
N1–N2
N1–C1
N2–C3
S1–C3
C1–C10
C3–O1
C3–N3b
1.958(4)
2.2498(12)
1.384(5)
1.295(5)
1.301(6)
1.714(5)
1.484(8)
1.331(5)
1.9584(16)
2.2453(5)
1.369(2)
1.300(2)
1.325(3)
1.760(2)
1.474(3)
1.338(3)
Bond angle
N1–Cu–S1
N1–Cu–N10
S1–Cu–S10
85.00(11)
79.9(2)
110.12(7)
85.11(5)
80.61(7)
109.21(2)
a
Fig. 3. Cyclic voltammogram of
7 in CH2Cl2 with 0.1 M tetrabutylammonium
Atom labels for both complexes correspond to the numbering scheme of 7 in
Fig. 1.
hexafluorophosphate as supporting electrolyte. Scan rate = 100 mV/s; potentials
referenced versus Fc+/Fc.
b
N3 the nitrogen of R1 group NHCH3.
The Cu of 7 occupies an N2S2 square plane provided by the N,N0-
bis(methylthiocarbamate)butane-2,3-diimine ligand with Cu–N1
and Cu–S1 bond distances of 1.958(4) and 2.2498(12) Å, respec-
tively. The S10 and N10 donors are symmetry generated as Cu1 sits
on the special position (0.5, y, 0.25) in the orthorhombic space
group Pbcn. A similar phenomenon occurs in 9, 11, 12, whereas
in 8 and 10 the asymmetric unit contains independent atoms in
the entire complex. Within the chelate ligand, bond distances are
ꢁ892 mV is found for the O nPr derivative 9. However, the
branched –OiPr complex 10 further destabilizes Cu(I) as indicated
by the CuII/I potential of 10 at ꢁ904 mV. Changes at the R2 position
results in no statistically significant change in the CuII/I potential
based on a comparison of 8 and 12, which are within 5 mV of each
other.
4. Discussion
consistent with a conjugated
p-system of alternating single and
double bonds, Fig. 2. The C3–S1, N1–N2, and C1–C10 bond distances
of 1.741(5), 1.384(5), and 1.484(8) Å, respectively, are typical of
single C–S, N–N, and C–C bonds. The shorter N1–C1 and N2–C3
bond distances of 1.295(5) and 1.301(6), respectively, reveal C=N
character. The sum of the four bond angles about the Cu is 360.0
(3)°. Complex 7 is rigorously planar with the largest deviation from
the best fit plane of all 17 non-hydrogen atoms of 0.118 Å for C3/
C30 and a standard deviation of only 0.061 Å.
A series of N,N0-bis(alkylthiocarbamate)butane-2,3-diimine Cu
(II) complexes as pendent alkoxy derivatives of Cu(ATSM) has been
synthesized and characterized. The synthetic methodology
involves condensation reaction of a dione with a hydrazinecar-
bothioic acid O-alkyl ester, analogous to the synthesis of H2ATSM
and related derivatives from diones and thiosemicarbazides. As
shown in Scheme 1, the hydrazinecarbothioic acid O-alkyl esters
are readily prepared from a variety of alcohol precursors in two
steps with carbon disulfide and hydrazine monohydrate. Notably,
all ligand syntheses are conducted open to the atmosphere in etha-
nol solution with facile purification by filtration and washing. The
simplicity of these methods and the variety of available alcohols
and diones make N,N0-bis(alkylthiocarbamate)butane-2,3-diimine
and similar ligands a potentially useful new class of ligands related
to the bis-thiosemicarbazone family.
3.3. Electrochemical studies
The cyclic voltammograms of 7–12 in dichloromethane each
show two reversible events assigned to CuIII/II and CuII/I couples,
Table 1. The E1/2 values for the CuIII/II and CuII/I events of 7 are
observed at +585 and ꢁ857 mV versus ferrocenium/ferrocene,
respectively, Fig. 3. Increasing the length of the R1 from –OMe to
–OEt and –O-octyl decreases the CuII/I potential of 8 and 11 to
ꢁ879 and ꢁ884 mV, respectively. A similar CuII/I potential of
A comparison of the room temperature EPR and UV–visible data
shows only small changes in the spectroscopic features of
complexes 7–12 as compared to similar bis-thiosemicarbazone

50
N.S. Vishnosky et al. / Inorganica Chimica Acta 461 (2017) 45–51
analogues, 13–17. Since the EPR spectra of 13, 15, and related com-
plexes did not change significantly between room temperature
powder data and 77 K frozen DMF solution data [31], only room
temperature powder data was evaluated for 7–12. The axial EPR
spectra of 13, Cu(ATSM), is indistinguishable from those of 8–12.
The reported g|| and g\ values of 2.115 and 2.038 for 13 fall within
the narrow ranges of 2.031–2.042 and 2.089–2.131 for 8–12,
Table 1, indicating no significant changes in the relative energies
of the d-orbital manifold. There is a small shift in the charge trans-
fer band energies upon substitution of –NHR with –OR. As shown
in Table 1, the high energy bands for 7 at 246 and 290 nm are
red shifted by 2340 and 2640 cmꢁ1 with respect to the bands at
261 and 314 nm in Cu(ATSM), 13. The lower energy band of 7 at
486 nm is blue shifted by 388 cmꢁ1 relative to the band at
477 nm in Cu(ATSM) [12]. The shifts are attributed to electronic
differences within the ligand framework and no solvent effects.
The spectra of 7 in DCM and DMSO are not substantially different.
A comparison of the structural parameters of 7 and 13 provide a
representative example of the similarities and differences of the N,
N0-bis(alkylthiocarbamate)butane-2,3-diimine and bis-thiosemi-
carbazone complexes. The selected bond distances and angles in
Table 2 reveal a highly similar structural core. The Cu–N1 and
Cu–S1 bond lengths in 7 of 1.958(4) and 2.2498(12) Å, respectively,
are statistically equivalent with the values of 1.9592(16) and
2.2474(5) Å in 13. Within the ligand framework, the bond dis-
tances are also statistically similar. Both complexes exhibit bond
distances consistent with alternating single and double bonds in
an extended conjugated network as depicted in Fig. 2 for 7. A com-
parison of bond angles associated with the metal-ligand core of 7
and 13 reveals values that are statistically equivalent or that vary
less than one degree.
commercially available alcohols and diones provides for a large
variety of new bis-thiosemicarbazone like complexes for future
development.
Acknowledgments
This research was supported in part by the National Science
Foundation (CHE-1361728). MSM thanks the Department of
Energy (DEFG02—08CH11538) and the Kentucky Research
Challenge Trust Fund for upgrade of our X-ray facilities.
Appendix A. Supplementary data
1H and 13C NMR of 1–6, UV–visible and EPR spectra of 9, exper-
imental crystallographic details including a table of crystal data
and structural refinement for 7–12, and ORTEP representations
and tables of bond distances and angles of 7–12 in PDF and crystal-
lographic data in CIF (CCDC 1517907–1517912). This material is
available free of charge via the Internet at http://pubs.acs.org. Sup-
plementary data associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.ica.2017.02.003.
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