Synthesis, characterization, density functional theory calculations, and activity of a thione-containing NNN-bound zinc pincer complex based on a bis-triazole precursor

Article abstract of DOI:10.1016/j.ica.2012.07.009

A novel ambidentate tridentate pincer ligand based on a bis-triazole precursor, was prepared, characterized, and metallated with ZnCl₂ to give a new tridentate NNN-bound pincer zinc(II) pincer complex: dichloro(η³-N,N,N)-[2,6-bis(3-[N-butyl]triazol-5-thione-1-yl)] pyridinezinc(II), [(NNN)ZnCl₂]. This compound has pseudo-trigonal bipyramidal geometry at the zinc(II) center and exhibits metal-ligand binding that contrasts with our previously reported SNS-bound systems despite the availability of these same donor atoms in the current ligand set. The zinc complex was characterized with single crystal X-ray diffraction, ¹H, ¹³C, and HSQC NMR spectroscopies, and electrospray mass spectrometry. The ligand precursors were characterized with ¹H, ¹³C, and HSQC NMR spectroscopies, and cyclic voltammetry, and were found to be redox active. Density functional calculations, which investigate and support the nature of the NNN binding suggest that the experimentally observed oxidation and reduction waves are not the result of a simple one-electron process. The zinc complex was screened for the reduction of electron-poor aldehydes in the presence of a hydrogen donor, 1-benzyl-1,4-dihydronicotinamide (BNAH), and it was determined that they enhance the reduction of 4-nitrobenzaldehyde. Quantitative stoichiometric conversion was seen for the reduction of pyridine-2-carboxaldehyde.

Full text of DOI:10.1016/j.ica.2012.07.009

Inorganica Chimica Acta 394 (2013) 310–321
Contents lists available at SciVerse ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Synthesis, characterization, density functional theory calculations, and activity
of a thione-containing NNN-bound zinc pincer complex based on a bis-triazole
precursor
John R. Miecznikowski a, , Jerry P. Jasinski , Matthew A. Lynn , Swapan S. Jain , Elizabeth E. Butrick ,
⇑
b
c
d
a
a
a
c
Anne Elise R. Drozdoski , Kerry A. Archer , Jason T. Panarra
a
Department of Chemistry and Biochemistry, Fairfield University, 1073 North Benson Road, Fairfield, CT 06824, USA
Department of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA
Department of Science and Mathematics, National Technical Institute for the Deaf, Rochester Institute of Technology, 52 Lomb Memorial Drive, Rochester, NY 14623, USA
Department of Chemistry, Bard College, P.O. Box 5000, Annandale-on-Hudson, NY 12504-5000, USA
b
c
d
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel ambidentate tridentate pincer ligand based on a bis-triazole precursor, was prepared, character-
Received 11 February 2012
Received in revised form 2 July 2012
Accepted 3 July 2012
ized, and metallated with ZnCl
2
to give a new tridentate NNN-bound pincer zinc(II) pincer complex:
3
dichloro(
g
-N,N,N)-[2,6-bis(3-[N-butyl]triazol-5-thione-1-yl)]pyridinezinc(II), [(NNN)ZnCl ]. This com-
2
pound has pseudo-trigonal bipyramidal geometry at the zinc(II) center and exhibits metal–ligand binding
that contrasts with our previously reported SNS-bound systems despite the availability of these same
donor atoms in the current ligand set. The zinc complex was characterized with single crystal X-ray dif-
Available online 20 July 2012
Keywords:
NNN pincer ligand
1
13
fraction, H, C, and HSQC NMR spectroscopies, and electrospray mass spectrometry. The ligand precur-
1
13
sors were characterized with H, C, and HSQC NMR spectroscopies, and cyclic voltammetry, and were
found to be redox active. Density functional calculations, which investigate and support the nature of the
NNN binding suggest that the experimentally observed oxidation and reduction waves are not the result
of a simple one-electron process. The zinc complex was screened for the reduction of electron-poor alde-
hydes in the presence of a hydrogen donor, 1-benzyl-1,4-dihydronicotinamide (BNAH), and it was deter-
mined that they enhance the reduction of 4-nitrobenzaldehyde. Quantitative stoichiometric conversion
was seen for the reduction of pyridine-2-carboxaldehyde.
Mononuclear Zn complexes
X-ray crystallography
Cyclic voltammetry
Density functional theory calculations
Aldehyde reductions
Ó 2012 Elsevier B.V. All rights reserved.
1
. Introduction
2 2 3
exhibit N S or N S coordination to Zn(II) ions [7]. Kellogg reported
Co(II) complexes that contain a trisubstituted benzene derivative,
3,5-bis(3-mercaptopropoxy)-N-[2-(1H-imidazol-4-yl)ethyl]benz-
amide as a model for LADH [12]. In another case, an LADH model
complex has been reported for an SSS-bound zinc complex [15],
but such a ligand donor environment is different than that found
within the enzyme’s active site. An N S donor set has been re-
3 2
ported by Kovacs for zinc complexes [11] and by Koch for cobalt
systems [13].
Walton [8] and Vahrenkamp [15] have reported NNN-bound
zinc(II) complexes as models for LADH. Walton reported the reac-
tion of an NNN-bound zinc(II) hydroxide complex with methanol
to give a zinc(II) methoxide complex. This reaction is related to
the displacement of ethanol by water in the zinc active site in liver
alcohol dehydrogenase. Vahrenkamp did report reactivity data for
the NNN-bound zinc(II) complexes for the reduction of electron-
poor aldehydes [15]. Vahrenkamp also published studies of zinc
Liver alcohol dehydrogenase (LADH) is a zinc metalloenzyme
that catalyzes the oxidation of alcohols to aldehydes and ketones
as well as the reverse reaction in which ketones and aldehydes
are reduced to alcohols [1–3]. The crystal structure of horse LADH
has been solved [4]. The catalytically active site contains one zin-
c(II) metal center, which is pseudo-tetrahedrally ligated with a la-
bile water molecule and a so-called ‘‘SNS’’ ligand environment
containing one N-histidine and two S-cysteine side chains. LADH
is an enzyme composed to two polypeptide chains where each
polypeptide chain contains active site histidine and cysteine resi-
dues that provide the nitrogen and sulfur atoms [5].
Several LADH models have been previously reported. [6–17].
Some zinc model complexes possess SNS donor atoms, but reactiv-
ity data was not reported in these studies [9,10,14]. Doł e˛ ga re-
ported tri-tert-butoxysilatethiolate and imidazole co-ligands that
3 2
complexes with N O donor atoms in which reactivity data for
the reduction of electron-poor aldehydes was reported [15].
In an effort to better understand the catalytic activity of LADH,
we have previously used a new and unique family of robust SNS
⇑
Corresponding author. Tel.: +1 203 254 4000x2125; fax: +1 203 254 4034.
E-mail address: jmiecznikowski@fairfield.edu (J.R. Miecznikowski).
0
020-1693/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ica.2012.07.009

J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
311
Fig. 1. SNS ligand precursors previously prepared by Miecznikowski et al. [16,17].
Fig. 2. Zinc-based SNS model complexes previously prepared by Miecznikowski et al. [16,17].
pincer ligands to model the structure and reactivity of the zinc ac-
tive site in LADH (Fig. 1) [16,17]. Ligands of this type have been
used in organometallic chemistry to prepare catalytically active
systems, and owing to the tridentate binding mode, compounds
that are robust [18,19]. Plus, to the best of our knowledge, such tri-
dentate pincer ligand systems have rarely been used in bio-in-
spired modeling chemistry, thereby giving us room to explore in
this area.
ligand exhibits a pseudo-tetrahedral geometry about the zinc(II)
center just as is found in the active site of LADH.
After obtaining reactivity results for the reduction of electron-
poor aldehydes, we determined that the SNS bis-imidazole Zn
complexes that do not contain a CH
tive than are those that do contain this connection (Fig. 2, 5). Con-
versely, the SNS bis-triazole Zn complexes with a CH (Fig. 2, 6)
2
linker (Fig. 2, 4) are more ac-
2
linker are more active than are the SNS bis-imidazole Zn com-
plexes without this methylene linker (Fig. 2, 4) [16,17]. We found
that the most active complex for the reduction of 4-nitrobenzalde-
hyde was an SNS-bound bis-triazole Zn complex with a CH linker
2
and n-butyl wingtip groups (Fig. 2, 6c).
In our past and current studies, we have employed various li-
gand precursors in an effort to gauge the impact of ligand flexibility
on the structure and reactivity of our zinc compounds. We have
prepared somewhat rigid ligand systems through the use of 2,6-
dibromopyridine as a ligand precursor (Fig. 1, 1a–c). In these com-
pounds, the imidazolyl groups are directly bound to the pyridine
unit such that the flexibility of the ligand is largely limited to rota-
tion about the CAN pyridinyl-imidazolyl bond. In addition, we have
prepared more flexible ligand systems by employing the starting
material 2,6-(dibromomethyl)pyridine to introduce a methylene
linker into the pincer ligand. Use of this precursor has allowed us
to compare the effect of ligand flexibility on substrate binding to-
ward the goal of reaching a better understanding of the catalytic
activity of LADH whether imidazole(Fig. 1, 1a–c and 2a–c) or triaz-
olyl functionalities (Fig. 1, 3a–c) are used to construct the ligand.
The thioimidazolyl S-donors have been reported by Parkin and Vah-
renkamp to model thiol-derived ligands in bio-inspired zinc chem-
istry [15,20,21]. Further, our ligands were prepared with imidazolyl
or triazolyl rings having wingtip alkyl groups of various sizes (iso-
propyl, neopentyl, and n-butyl) as shown in Fig. 1 in an effort to
understand how ancillary alkyl groups affect the ability of the mod-
el zinc systems to reduce aldehydes. When 2,6-(dibromometh-
yl)pyridine was used as a starting material, we were able to fine-
tune further the electronic environment imparted by our ligand
set by using imidazole- and triazole-based precursors in the prepa-
ration of the pincer ligand precursor (Fig. 1, 1a-c, 2a–c, and 3a–c).
Previously, we have prepared zinc model compounds that
contain these ligands [16,17] (Fig. 2). In these instances, the pincer
Based on our previous findings regarding the reactivity of the
compounds in Fig. 2, we focused our attention in our current work
on preparing novel ligand precursors that possess two thione-con-
taining triazole moieties [22] bound directly to the pyridinyl unit.
Conceivably, these novel ligand precursors can coordinate to a me-
tal center via either the SNS or NNN donor atoms in the ligand
depending on intraligand as well as metal–ligand bonding con-
straints. Therefore, we present here the synthesis, spectroscopic
and electrochemical characterization, computational study, and
activity screening of an LADH model system in which our novel tri-
dentate bis(thiotriazolyl)pyridine pincer ligand, in contrast to our
previous findings with a similar ligand system, uses only its N
atoms to coordinate to a Zn(II) center.
2. Experimental
2.1. General procedures
All reagents used are commercially available and were used as
received. All of the reagents and solvents were purchased from
Acros Organics except for diethyl ether, sodium acetate, and zinc
chloride, which were purchased from Fisher, and pyridine
2-carboxaldehyde which was purchased from Alfa Aesar.

3
12
J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
1
2
,6-Bis(1-triazolo)pyridine (btpy) and BNAH were prepared as
using H NMR spectroscopy. All data are averages of at least two
reported previously [22,23].
runs.
NMR spectra were recorded at 25 °C on a Bruker Avance
3
00 MHz NMR spectrometer. Spectra were referred to the solvent
2.4. GAUSSIAN 03 calculations
residual peak. Electrospray mass spectrometry was performed on
a Varian LC-MS instrument using nitrogen as the drying and nebu-
lizing gas. Cyclic voltammetry experiments were performed using
a Cypress Electroanalytical System with a silver wire reference
electrode, a glassy carbon working electrode, and a platinum coun-
ter electrode. The supporting electrolyte for the cyclic voltammetry
experiments was tetra-N-butylammonium tetrafluoroborate. The
solvent for the cyclic voltammetry experiments was dimethyl sulf-
oxide. The ferrocenium/ferrocene couple was used as an internal
reference; reduction potential values were corrected by assigning
the ferrocenium/ferrocene couple to 0.40 V versus SCE. IR spectra
were collected using a Thermo Nicolet AVATAR 380-FT-IR with a
SMART SPECULATR reflectance adaptor. C, H, N elemental analyses
were performed by Atlantic Microlab Inc. (Norcross, GA).
G
AUSSIAN 03 was used to perform single-point calculations and
DFT geometry optimizations using the B3LYP hybrid functional
with the 6-31G basis set as provided with the software [26]. Cal-
culations were performed on the unbound and metal-bound li-
gands with R = Me in all cases. Structures were first optimized in
the gas phase as neutral and for the electrochemical analysis, as
⁄
s 2
cationic species under the C , C , and C2v point groups. Frequency
analyses were performed on the optimized structures to determine
whether or not they represented true minima. Most structures
indicated either no imaginary frequencies or small frequencies
ꢀ1
on the order of ꢁꢀ10 cm . The largest imaginary frequencies
ꢀ1
determined were approximately ꢀ40 cm
and were found for
the ligand and metal-bound systems of C2v symmetry. Calculations
were also performed in order to obtain an energy profile of the free
ligand across the range of pyridinyl–triazolyl dihedral angles pos-
2.2. Crystallographic analyses
2 s
sible under the C , C , and C2v point groups.
Single-point SCRF calculations using DMSO via the CPCM sol-
vent model were performed on the gas-phase optimized structures
using the ‘‘radii = uff’’ and ‘‘nosymmcav’’ directives. Oxidation
potentials were computed by finding the difference in the total free
A crystal of 9 (vide infra) was mounted on a CryoLoop (Hampton
Research) and placed in a ꢀ100 °C compressed air stream on an
Agilent Gemini-EOS Single Crystal Autodiffractometer at Keene
State College (Keene, NH). Crystallographic data were collected
energies in solution for the neutral and cationic species. These
DG
using graphite monochromated 0.71073 Å Mo K
a radiation and
values were then referenced to the absolute SCE potential in DMSO
by subtracting 3.83 V (the established correction to SHE in DMSO)
and 0.241 V (the difference between SHE and SCE) [27].
integrated and corrected for absorption using the CrysAlisRed (Ox-
ford Diffraction, 2010 software package) [24]. The structures were
solved using direct methods and refined using least-square meth-
ods on F-squared [25]. All other pertinent crystallographic details
such as h, k, l ranges, 2h ranges, and R-factors can be found in
Table 1.
2
2
.5. Syntheses
.5.1. Preparation of 2,6-bis(3-N-[butyl]triazol-1-yl)pyridine iodide [7]
In a 25 mL round-bottom flask, 0.499 g (1.87 mmol) of 2,6-
2
.3. Reactivity
bis(1-triazolo)pyridine (btpy) was combined with 1.34 g
7.27 mmol) of 1-iodobutane. The neat mixture was stirred at
60 °C for 18 h during which time a white precipitate formed.
The solid was taken up in dichloromethane (20 mL) and precipi-
tated with diethyl ether. The solid precipitate was collected via
vacuum filtration and was subsequently taken up in methanol
and re-precipitated with diethyl ether. The off-white solid was col-
lected via vacuum filtration and was washed with diethyl ether
(
1
In a typical reaction, 0.1 mmol of an electron-poor aldehyde (4-
nitrobenzaldehyde or pyridine 2-carboxaldehyde), 0.2 mmol of
BNAH, and 0.1 mmol of the zinc complex or 0.1 mmol ZnCl were
dissolved in 3 mL of CDCl . The reaction was heated at reflux. Ali-
2
3
quots of the reaction were taken at certain times and analyzed
Table 1
Crystal and structure refinement data for C17
H23Cl
2
7
N S
2
Zn [9].
(
25 2 7
3x, 30 mL each). Yield: 0.45 g (41%). Anal. Calc. for C17H I N
Formula
C
17
H
23Cl
2 7
N S
2
Zn
(581.24): C, 35.13; H, 4.34; N, 16.87. Found: C, 35.60; H, 4.27; N,
17.46%.
FW (g/mol)
Temperature (K)
Wavelength (Å)
Crystal system
Space group
a (Å)
525.81
173(2)
0.71073
monoclinic
P2(1)/c
1H NMR (DMSO-d
6
, 300 MHz) d 11.39 (s, 2H, triazole, CH), 9.66
3
(
s, 2H, triazole, CH), 8.66 (m, 1H, pyridine CH), 8.31 (d, ( J = 8.1 Hz),
H, pyridine CH), 4.46 (m, 4H, n-butyl CH ), 1.97 (m, 4H, n-butyl
CH ), 1.41 (m, 4H, n-butyl CH ), 0.96 (m, 6H, n-butyl CH
{ H} NMR (DMSO-d , 75 MHz), d 145.96 (triazole CH), 145.53 (pyr-
idine CH), 142.02 (triazole CH), 115.21 (pyridine CH), 48.22 (n-bu-
2
2
13
11.3556(6)
2
2
3
).
C
1
b (Å)
21.8575(10)
10.3486(4)
113.159(5)
2361.6(2)
4
1.461
1.511
1080
6
c (Å)
o
b ( )
Volume (Å)3
tyl CH
CH ).
IR bands (reflectance, powder),
2
), 30.75 (n-butyl CH
2
2
), 18.79 (n-butyl CH ), 13.31 (n-butyl
Z
3
3
ꢀ1
r (calc) (g/cm )
m
max/cm (intensity): 2954.56
Absorption (mmꢀ1)
(
br), 1611.74 (m), 1565.58 (m), 1501.02 (m), 1457.35 (m),
F(000)
Crystal size (mm )
Theta range ( )
Reflections/unique
1
446.28 (m), 1405.07 (m), 1367.81 (w), 1207.40 (s), 1065.41 (m).
3
0.24 ꢂ 0.12 ꢂ 0.06
o
997.90 (w), 969.67 (s), 911.95 (w), 807.03 (vs), 780.09 (m),
742.13 (w), 721.97 (w), 664.16 (m), 618.10 (vs).
3.41–32.33
32460/7829
0.0444
R
int
Absorption correction
Maximum/minimum
Reference method
multi-scan
2
.5.2. Preparation of 2,6-bis{[N-butyl]triazole-1-ylidene-2-
1.0000/0.85028
full matrix least squares on F2
7829/0/293
1.097
0.0722
0.1755
thione}pyridine [8]
In a 250 mL round-bottom flask, 0.501 g (0.862 mmol) of 7 was
combined with 0.215 g (2.63 mmol) sodium acetate and 0.747 g
Data/restraints/parameter
Goodness-of-fit (GOF) on F2
R
1
indices (I > 2s)
(
23.3 mmol) sulfur in acetonitrile (35 mL). The solution was heated
wR
2
at reflux for 12 days. After heating, the product was vacuum fil-
tered to remove excess sulfur. The acetonitrile solution was col-
Peak/hole (e/Åꢀ3)
2.46 and ꢀ0.77

J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
313
lected and the solvent was removed under reduced pressure. The
product was dissolved in dichloromethane and was filtered to re-
move excess sodium acetate. The dichloromethane solvent was re-
moved under reduced pressure. Yield: 0.33 g (98%). Anal. Calc. for
(C@S), 148.63 (pyridine Cipso), 142.23 (triazole CH), 140.66 (pyri-
dine CH), 120.54 (pyridine CH), 45.03 (n-butyl CH ), 29.70 (n-butyl
CH ), 19.12 (n-butyl CH ), 13.48 (n-butyl CH ).
2
2
1
2
3
3
4
H NMR (MeOH-d , 300 MHz) d 8.74 (d ( J = 8.1 Hz), 2H, pyri-
3
C
17
H
23
N
7
S
2
ꢃ0.5 CH
2
Cl
2
ꢃ0.5 H
2
O (389.54): C, 47.66; H, 5.71; N,
dine CH), 8.29 (t ( J = 8.1 Hz), 1H, pyridine CH), 4.15 (t
3
2
2.17. Found: C, 47.94; H, 5.52; N, 22.96%.
( J = 7.2 Hz), 4H, n-butyl CH
4H, n-butyl CH ), 1.01 (m, 6H, n-butyl CH
IR bands (reflectance, powder), mmax/cm (intensity): 3445.41
2
), 1.87 (m, 4H, n-butyl CH
2
), 1.45 (m,
1
H NMR (DMSO-d
6
, 300 MHz) d 8.83 (s, 2H, triazole CH), 8.29
2
3
).
ꢀ
1
(
m, 1H, pyridine CH), 8.20 (m, 2H, pyridine CH), 4.01 (m, 4H, n-bu-
tyl CH ), 1.75 (m, 4H, n-butyl CH ), 1.32 (m, 4H, n-butyl CH ), 0.92
C{ H} NMR (DMSO-d , 75 MHz),
66.19(C@S), 148.58 (pyridine Cipso), 142.20 (triazole CH), 140.62
), 29.65
2
2
2
(br), 2959.82 (w), 1604.70 (m), 1565.35 (m), 1454.74 (s), 1409.52
(s), 1379.28 (m), 1335.28 (s), 1296.18 (m), 1262.81 (w), 1221.01
(m), 1152.21 (m), 1082.01 (m), 1059.16 (w), 1005.60 (m), 869.97
(w), 814.04 (vs), 736.29 (w), 664.72 (m), 619.30 (m).
13
1
(
m, 6H, n-butyl CH
3
).
6
d
1
(
(
pyridine CH), 120.46 (pyridine CH), 44.98 (n-butyl CH
n-butyl CH ), 19.08 (n-butyl CH ), 13.43 (n-butyl CH ).
IR bands (reflectance, powder), max/cm (intensity): 3427.16
br), 1651.67 (w), 1622.04 (m), 1598.80 (m), 1559.58 (w),
451.85 (m), 1406.46 (s), 1334.39 (m), 1297.18 (w), 1236.07
2
2
2
3
ꢀ1
m
(
1
3. Results and discussion
(
(
w), 1204.89 (w), 1158.34 (w), 119.73 (w), 1071.78 (w), 1053.87
w), 1007.96 (w), 987.58 (w), 966.40 (w), 946.83 (w), 874.89 (w),
3.1. Syntheses and spectroscopy
8
12.43 (m), 794.90 (s), 728.91 (w), 669.19 (w).
The synthesis of 2,6-bis{[N-butyl]triazole-1-ylidene-2-thi-
one}pyridine, 8, was accomplished according to the steps shown
in Scheme 1. 2,6-Bis(1-triazolo)-pyridine (btpy) was prepared fol-
lowing a published route [22], and was then treated with 1-iodo-
butane to produce a ligand precursor salt that is more soluble in
organic solvents than btpy. Crabtree reported that a wingtip group,
n-butyl in this case, affects the solubility and catalytic activity of
the metal complexes [28]. As such, we find that ligand precursor
7 is soluble in DMSO, methanol, acetonitrile, and water.
Ligand precursor salt 7 was reacted first with a mild base, so-
dium acetate, and then with elemental sulfur in refluxing acetoni-
trile to form the bis-thione ligand precursor, 8, which is soluble in
DMSO, dichloromethane, chloroform, acetone, acetonitrile, and
methanol. As shown in Scheme 1, isomers of 8 in which the S
atoms of the thiotriazole moieties are oriented in a relatively cis
or trans fashion to the pyridinyl N atom are possible. As will be dis-
cussed in the computational section, the structure of compound 8
can be idealized and considered under several point groups. It
could be planar (C2v symmetry) with both S atoms in either cis or
3
2
.5.3. Preparation of dichloro(
g
-N,N,N)-[2,6-bis(3-[N-butyl]triazol-5-
Zn] [9]
A round-bottom flask was charged with 0.102 g (0.263 mmol) of
, 0.0829 g (0.608 mmol) of ZnCl and 10 mL of dichloromethane.
2 7 2
thione-1-yl)]pyridinezinc(II) [C17H23Cl N S
8
2
The solution mixture was refluxed for 24 h. After this time, the
dichloromethane was removed under reduced pressure. Single
crystals for X-ray diffraction were grown by a slow vapor diffusion
of diethyl ether into an acetonitrile solution containing the zinc
complex. Yield: 0.11 g (81%). Electrospray MS (MeOH, 20 V, posi-
tive ion mode (m/z): Expected: 488.0 (100%) [C17
+
H23ClN
7
S
2
Zn] ,
+
Found: 487.9 (100%) [C17
23Cl Cl ꢃH O (525.83): C, 34.38; H, 4.33; N, 15.59.
ZnꢃCH
Found: C, 33.73; H, 3.79; N, 16.11%.
7 2
H23ClN S Zn] . Anal. Calc. for
C
17
H
2
N
7
S
2
2
2
2
1
H NMR (DMSO-d
m, 1H, pyridine CH), 8.20 (m, 2H, pyridine CH), 4.03 (m, 4H, n-bu-
tyl CH ), 1.80 (m, 4H, n-butyl CH ), 1.33 (m, 4H, n-butyl CH ), 0.93
m, 6H, n-butyl CH ). C{ H} NMR (DMSO-d , 75 MHz), d 166.24
6
, 300 MHz) d 8.83 (s, 2H, triazole CH), 8.29
(
2
2
2
13
1
(
3
6
Scheme 1. Preparation of ligand precursors.

3
14
J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
trans orientations relative to the pyridinyl N atom. If the system
were nonplanar, the highest order point groups under which it
Attenuated total reflectance IR spectra were collected for 7–9.
All compounds present unique IR spectra. The C@S stretch occurs
ꢀ1
can be treated are C
ward and the other backward relative to the pyridinyl unit, the sys-
tem will have C symmetry. If both thiotriazole units are rotated in
the same direction relative to the pyridinyl moiety, the system has
symmetry. The calculated energy barrier to thiotriazole ring
2
s
and C . If one thiotriazole unit is rotated for-
at 1158 cm for the bis-triazole bis-thione precursor, 8. This data
is consistent with the C@S stretching frequencies that we have re-
ported previously for similar compounds [17].
2
Complex 9 was analyzed with H, 13C, and HSQC NMR spectros-
1
1
13
C
s
6
copy in DMSO-d . The H and C NMR spectra of the zinc complex
rotation, to be discussed shortly, is rather low (ca. 9 kcal/mol) so
averaging of the NMR signals for the two rings is expected to occur.
We are indeed unable to differentiate these various conformations
using NMR spectroscopy. We have been unable to obtain a solid-
state structure of 8.
are similar to those for the ligand precursor, 8, with little shift in
the resonances. Such a result is to be expected since no hydrogen
or carbon atoms are displaced or added upon metallation with zin-
c(II) chloride. Electrospray mass spectrometry data, described be-
low, also verifies this result.
Ligand precursor, 8, subsequently reacts with excess ZnCl
2
in
In addition, the 1H NMR spectrum of complex 9 was also ac-
refluxing CH Cl to afford zinc complex 9 (Eq. (1)). Excess ZnCl
2
2
2
4
quired in a less polar and weakly coordinating solvent, MeOH-d ,
was used to drive the reaction to completion. Ligand precursor 8
can conceivably coordinate to the zinc(II) metal center via the
SNS donor atoms or via the NNN donor atoms, but we find in the
current case that it binds exclusively through only the three avail-
able N atoms of the pyridinyl and thiotriazolyl units
to verify that the tridentate pincer ligand is not displaced from
the coordination sphere of zinc. In the H NMR spectrum that was
1
acquired in MeOH-d
4
, the triazine CAH proton resonance was not
observed. We were not able to prepare a sample of 9 in MeOH-d
that was concentrated enough to acquire a C NMR spectrum.
4
1
3
.
ð1Þ
The driving force for the metallation is the formation of neutral
zinc complex 9, which is sparingly soluble in CH Cl . Off-white sin-
2 2
ESI-MS data for complex 9 was collected with a cone voltage of
0 V and 70 V. The predominant feature in the spectrum of 9 is that
of the [(NNN)ZnCl] ion. This finding suggests that the one
chloride ligand is displaced in the mass spectrometer and that
the tridentate ligand remains coordinated to the zinc(II) ion. The
isotopic pattern in the mass spectrometry data fits the assigned
structure.
+
gle crystals suitable for X-ray diffraction were grown by allowing
diethyl ether vapor to slowly diffuse into an acetonitrile solution
containing the zinc complex. All of the reactions (Scheme 1 and
Eq. (1)) were performed in air and proceeded with yields at or
above 41%. Zinc complex 9 is soluble in dimethyl sulfoxide, aceto-
nitrile and methanol and is sparingly soluble in dichloromethane
and chloroform.
3.2. X-ray crystallography
Ligand precursors 7 and 8 and zinc complex 9 were character-
1
13
ized using H, C, and HSQC NMR spectroscopy. For all com-
pounds, only one set of resonances was detected. For 7, the
pyridine Cipso was not observed. The 13C NMR of 8 shows a reso-
nance at d ꢁ166 ppm, that is consistent with C@S formation
The solid-state structure of 9 is shown in Figs. 3 and 4. The com-
plex features a tridentate NNN donor ligand and pseudo-trigonal
bipyramidal geometry about the zinc(II) center.
In a five-coordinate geometry, the idealized dihedral angles for
the trans basal angle is 158.0°. The distance between Del values
for trigonal bipyramid (TP) and square pyramid (SP) structures along
the Berry coordinate is 224.7. For complex 9, using Cl1 as the pivot
atom, the TP to SP percentage along the Berry pseudorotation is
[
ꢁ
16,17,19]. The ligand precursor, 7, contains a resonance at d
11.4 ppm in its 1H NMR spectrum indicative of a deshielded
CAH proton. This feature is absent in the spectrum of compound
in which the proton has been replaced by a sulfur atom.
8
Fig. 3. Molecular structure of 9 showing the atom labeling scheme and 30% probability ellipsoids.

J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
315
Fig. 4. Packing diagram of 9 viewed along the b axis. Hydrogen atoms have been deleted for clarity.
2
9.5. This value should be zero for a true Berry rotation [29]. The Ber-
the NNN donor atoms in the ligand precursor do not coordinate to
a single metal atom in a tridentate fashion. Given the difference in
metal–ligand coordination that we observe here, we propose that
it is the presence of the sterically bulky n-butyl wingtip groups
in 9 that encourages the ligand to coordinate to a single zinc center
in a tridentate fashion.
Various bond lengths and angles for 9 are given in Table 2. The
carbon–sulfur bond lengths in 9 are between what is normally
associated with a CAS single bond (1.83 Å) and a C@S double bond
(1.61 Å) [36]. In 9, the bond lengths of 1.653 Å and 1.647 Å are clo-
ser to that of a C@S double bond than a CAS bond. The ZnAN (pyr-
idine) bond length is consistent with the zinc–nitrogen bond
lengths that we and others have previously reported [16,17,37].
The zinc–nitrogen (triazole) bond lengths are about 0.1 Å longer
than that of a zinc–nitrogen (triazole) bond length in a previously
reported zinc–triazole complex [38]. The zinc–chloride bond
ry exchange coordinate, based on observed stereochemical nonrig-
idity associated with five-coordinate species, has been applied to a
ground state trigonal bipyramid structure by involving a concerted
axial-equatorial bond-bending motion that takes the structure to a
square planar transition along a low energy pathway. The motion in-
volves an intramolecular, simultaneous exchange of both axial and
equatorial ligands and referred to as the Berry pseudorotation. A plot
of the axial angle, h15, and the equatorial angle, h24, versus the dihe-
dral angle d24 based on the structural distortion of cyclic phospho-
rous as one proceeds along a line (referred to as the Berry
coordinate), from the idealized square or rectangular pyramid to-
ward a trigonal bipyramid shape provides data for this assignment.
The rational is supported by the perturbing influence of packing ef-
fects and ligand constraints, if modest, will adjust the penta-coordi-
nated structure along its lowest energy pathway. The dihedral angle,
d24 defining the abscissa in the plot is the angle formed between the
normal to the trigonal bipyramid faces 124 and 245 that have the
common equatorial edge 24 and most intimately associated with
the Berry exchange coordinate. This angle has a value of 53.1° for
an idealized trigonal bipyramid, but becomes 0° as edge 24 disap-
pears on forming the square (or rectangular) pyramid.
Table 2
Selected bond-lengths and angles (esd) for 9.
(1)
Zn(1)–N(1) (Å)
Zn(1)–N(3) (Å)
Zn(1)–N(6) (Å)
Zn(1)–Cl(1) (Å)
Zn(1)–Cl(2) (Å)
C(6)–S(1) (Å)
2.166(3)
2.200(3)
2.165(3)
2.2764(12)
2.3021(10)
1.653(4)
In work related to our own, Turnbull and co-workers have re-
ported the coordination of btpy, our ligand precursor, to a cop-
per(II) ion [22]. They reported an extended coordination
polymeric network. The triazole nitrogen atom in btpy coordinates
to a copper(II) ion to form an extended coordination polymer. The
triazole N atom that coordinates to the copper(II) ion in btpy is
coordinated to the n-butyl group in complex 9 in our work [22].
Other studies have shown polymeric, ring, and/or zig-zag chain
structures when the btpy ligand is coordinated to Rh(II), Ag(I),
Fe(III), Zn(II), or Cu(II) ions [30–35]. In all of these complexes, the
transition metal ion is coordinated to one of the triazole nitrogen
donor atoms and other ligands [22,30–35]. In all of these com-
plexes, the metal atoms bind to the triazole N to which the n-butyl
groups are bound in our complex 9. Thus, when btpy is metallated,
C(8)–S(2) (Å)
1.647(4)
N(6)–Zn(1)–N(1)
N(6)–Zn(1)–N(3)
N(1)–Zn(1)–N(3)
N(6)–Zn(1)–Cl(1)
N(1)–Zn(1)–Cl(1)
N(3)–Zn(1)–Cl(1)
N(6)–Zn(1)–Cl(2)
N(1)–Zn(1)–Cl(2)
N(3)–Zn(1)–Cl(2)
Cl(1)–Zn(1)–Cl(2)
72.35(12)
144.49(13)
72.24(12)
95.98(11)
119.24(10)
103.48(11)
98.56(10)
122.22(9)
97.83(10)
118.42(4)

3
16
J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
lengths are consistent with those of single bonds in five-coordinate
zinc complexes. [39].
The R-factor of 1 was 0.07. The higher R-factor for 9 was attrib-
uted to the disorder in the n-butyl groups present in the zinc com-
plex [17,40].
we present here an energy analysis of various conformations of the
unbound ligand and bound metal–ligand systems to support our
current findings followed by an analysis of the oxidation feature
we observe in the cyclic voltammogram.
The four five-membered rings present in the structure of 9 (i.e.
the two triazolyl units and the two five-membered rings that in-
clude the zinc center) are essentially planar with maximum devia-
tions from the mean planes as follows: Zn1/N1/C1/N2/N3
3
.3.1. Computational analysis of unbound conformations of 2,6-bis{[N-
methyl]triazole-1-ylidene-2-thione}pyridine
Given the lack of methylene linkers in our current ligand sys-
tem, the only way in which the relative orientations of the N and
S donor atoms can be modified is by way of rotation about each
of the two CAN pyridinyl–triazolyl bonds in the molecule. Through
the use of molecular symmetry, we chose to model our ligand set
under several point groups in order to understand the overall ener-
getics of the system as well as to deduce intramolecular interac-
tions that give rise to any energy preferences. These point groups
are: C2v (the entire molecule, with the exception of several of the
(
0.0042(15) Å-Zn1); Zn1/N1/C5/N5/N6 (ꢀ0.024(4) Å-N6); N2/N3/
C7/N4/C6 (ꢀ0.006(4) Å-N4); N5/N6/C9/N7/C8 (ꢀ0.005(5) Å-C8).
The atoms that comprise the six-membered pyridine ring are
coplanar with each other with a maximum deviation from the
mean plane of symmetry by 0.005(5) Å-C3, C4.
There is a large residual peak in the final difference map (2.46 e/
ꢀ
3
Å
(
) and it is 0.65 Å from Cl1. The large minimum residual peak
ꢀ3
ꢀ0.77 e/Å ) is 0.46 Å from Cl2.
2
H atoms on the pendant methyl groups, is flat), C (the axis of rota-
tion passes through the pyridinyl N atom and the C atom at the 4
position of this ring; one of the triazolyl rings is rotated such that
the thionyl S atom is in front of the pyridinyl ring while the other is
3
.3. GAUSSIAN 03 modeling of ligand, metal–ligand binding, and cyclic
voltammetry results
positioned so that the S atom is behind the pyridinyl ring), and C
s
Recently, we have reported several LADH model complexes con-
structed of either a bis(imidazolylthione)pyridine or a bis(triazol-
ylthione)pyridine ligand, the latter containing CH linkers within
2
(the plane of symmetry is perpendicular to the plane of the pyrid-
inyl ring and passes through the pyridinyl N and 4-position C
atoms; both of the triazolyl rings are rotated so that the S atoms
are oriented in the same direction relative to the pyridinyl ring).
In performing our computations, we have chosen to define the
dihedral angle between the pyridinyl and thiotriazole rings as
being 0° when the ligand as a whole is flat and the thionyl S atoms
are located in a cis orientation to the pyridinyl N atom.
Shown in Fig. 5 is the energy profile obtained by optimizing the
structure of the free ligand at fixed pyridinyl–thiotriazolyl dihedral
s 2
angles from 0° to 180° at 5° intervals under the C and C point
groups. The energies of all of the optimized structures are pre-
sented relative to the structure with lowest energy, the global min-
the ligand set, bound to a zinc center [16,17]. In each of these sys-
tems, the tridentate ligand was found to bind to the metal center
via the pyridinyl N atom and the thionyl S atoms. For the imidaz-
olyl-containing complexes [16], the only atoms available for bond-
ing to the metal center are these three donor atoms whereas two
additional N atoms are present in the triazole system [17]. Aside
from the N-bound alkyl groups in our previous triazole-based re-
port and our current findings, we note that there are two main
structural differences between those compounds and the ones pre-
sented herein. First, the N atoms of the triazole employed in our
current report are in the 1, 3, and 4 positions relative to the pen-
dant alkyl group whereas in our previous study they were located
in the 1, 2, and 4 positions. Second, the organic system in our cur-
2
imum of the C -symmetric structure. As is evident from the plot,
the energy profile for the optimizations under each of the point
groups possesses two minima and three maxima. The global min-
imum is located at a dihedral angle of ca. 145° and a local mini-
mum is found at ca. 45°. The global maximum occurs at 0° and
local maxima are found near 90° and 180°. Furthermore, across
2
rent report does not possess CH linkers between the pyridinyl and
triazolyl moieties whereas the ligand we reported previously does
have such a connection. Given the structural differences that we
observe through the use of these two similar tridentate ligand sys-
tems, we were interested in understanding the geometric and elec-
tronic factors that lead to the difference in the preferred metal–
ligand bonding configurations in each of these systems. Therefore,
the range of dihedral angles, the C
2
-symmetric structures are found
to be slightly more stable than are those with C
s
symmetry.
Shown in Fig. 6 are several of the optimized structures of 2,6-
bis{[N-methyl]triazole-1-ylidene-2-thione}pyridine, their relative
2 s
Fig. 5. Relative total energy vs. pyridinyl–thiotriazolyl dihedral angle for 2,6-bis{[N-methyl]triazole-1-ylidene-2-thione}pyridine modeled under C and C symmetries.

J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
317
Fig. 6. Various geometry-optimized conformations of 2,6-bis{[N-methyl]triazole-1-ylidene-2-thione}pyridine, their relative energies, and structural parameters.
energies, and pertinent structural parameters. In the most stable
system (C symmetry), shown at the bottom of this figure, both
of the thionyl S atoms are oriented relatively trans to the pyridinyl
N atom with the triazolyl rings rotated such that they deviate from
coplanarity with the pyridine fragment by 143.6°. The analogous
by 3.54 Å, the closest SAS distance possible given the imposed con-
2
straints. In the other structures with a relatively cis-pyridinyl
N-thionyl S orientation, the SAS distance is on the order of 4–5 Å.
Our inference from this analysis is that the preferred orientation
of the triazolyl rings relative to the pyridinyl ring in the unbound
system influences how the ligand as a whole binds to the metal
center. With the S atoms oriented in a trans manner relative to
the pyridinyl N atom, approach of the metal center to this pre-
ferred ligand conformation leads to the NNN binding that we ob-
serve rather than the SNS binding that we have presented
previously. While this finding is certainly an important factor,
the actual binding of the ligand to the metal center must also be
investigated. We therefore present in the next section an investiga-
tion of the metal–ligand system in which the zinc center binds
either in an NNN or an SNS fashion under these various symme-
tries to round out our understanding of the structural energetics
of this complex.
s
C -symmetric structure (not shown in the figure) is a mere
0
.3 kcal/mol less stable than this C conformation. Confining these
2
trans systems to be completely flat with a pyridinyl–thiotriazolyl
dihedral angle of 180° destabilizes the molecule by approximately
2
.1 kcal/mol relative to the global minimum.
Rotation of the thiotriazolyl rings such that the thionyl S atoms
are both relatively cis to the pyridinyl N atom destabilizes the mol-
ecule relative to the trans structures. Local minima are found at
2 s
dihedral angles of 42.7° (C ) and 46.2° (C ); these local minima
are 3.9 (C ) and 5.6 (C ) kcal/mol less stable than the global mini-
2
s
mum. The global maximum occurs when the entire ligand system
is flat with a dihedral angle of 0°. This structure is nearly 9 kcal/mol
above the global minimum.
We ascribe this relative energy ordering to several features: the
electrostatic interaction between the negatively charged electron-
3.3.2. Computational analysis of various bound conformations of
3
dichloro(
g
-N,N,N)-[2,6-bis(3-[N-methyl]triazol-5-thione-1-
donor thionyl S atoms, the establishment or disruption of
p
-conju-
yl)]pyridinezinc(II)
gation between the pyridinyl and thiotriazolyl rings, and steric
interactions between H atoms on these rings. Our calculations
show that the S atoms have Mulliken atomic charges on the order
of ꢀ0.4. The repulsion between these common negative charges
gives rise to an intramolecular repulsion between the thionyl moi-
eties such that the conformations in which the S atoms are far
apart, which occurs at large pyridinyl–thiotriazolyl dihedral angles,
are the most stable. The trend in intramolecular SAS distances pre-
sented in Fig. 6 correlates well with this observation. In the most
stable structure, the S atoms are 8.69 Å from each other. Although
the S atoms are a bit farther from each other (8.93 Å) in the next
most stable structure, the planarity of this system increases the
non-bonded interactions between the pyridinyl and thiotriazolyl
In computing the relative energies of the NNN- and SNS-bound
systems, we chose to perform our calculations under the same
point groups that were used to investigate the free ligand. Shown
in Fig. 7 are the six geometry-optimized structures and their rela-
tive energies. On the whole, all of the NNN-bound systems are
more stable than the SNS-bound complexes. The most stable struc-
ture is the NNN-bound structure that possesses C2v symmetry,
2 s
with the C and C structures being 0.04 and 0.35 kcal/mol less sta-
ble, respectively. All of these structures exhibit a pseudo-trigonal
bipyramidal coordination environment at the zinc center with
the two bound nitrogen atoms of the triazolyl rings occupying
positions that are roughly axial. The pyridinyl N atom and the Cl
atoms are located in equatorial positions.
rings; thus the maximization of
these rings is not the deciding factor in determining the most sta-
ble structure. In the least stable structure the S atoms are separated
p
-bonding interactions across
Given our previous reports of SNS-bound zinc centers, we were
surprised to find that for the current tridentate ligand, the SNS
binding mode gives rise to systems that are considerably less sta-

3
18
J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
Fig. 7. Various geometry-optimized conformations of dichloro(g
3-N,N,N)-[2,6-bis(3-[N-methyl]triazol-5-thione-1-yl)]pyridinezinc(II) and their relative energies.
ble. The most stable structure with this binding mode possesses C
2
the tridentate ligand binds in an SNS fashion. Given that a d10 Zn(II)
center would not have any ligand field-type preference for a given
geometry, we note that the coordination sphere of the metal is pre-
dominantly driven by ligand constraints and metal–ligand bonding
interactions, including the formation of five-membered rings with
the zinc atom and the nitrogen atoms of the pyridinyl and triazolyl
fragments. Under the five-coordinate arrangement, the three N
atoms are positioned such that they can be arranged in a meridio-
symmetry and is 20.6 kcal/mol less stable than is the most stable
NNN-bound system. The zinc center in this molecule possesses a
pseudo-trigonal bipyramidal coordination environment with the
sulfur atoms in approximately axial positions. The least stable
structure, located nearly 40 kcal/mol above the most stable NNN-
bound system, also has a pseudo-trigonal bipyramidal zinc center,
but in this structure the Cl atoms are axially bound with the SNS
atoms found in equatorial positions. The one structure that we lo-
cated that does not have this coordination environment is the SNS-
nal fashion about the metal center and the
gand is preserved.
p conjugation of the li-
s
bound system that possesses C symmetry. In this structure, the Cl
and S atoms form a pseudo-tetrahedral environment about the Zn
center; the pyridinyl N atom is located 3.45 Å away from the metal
center. This structure is reminiscent of an SNS-bound structure
that we have previously reported [16]. In that system, two thionyl
sulfur atoms, one pyridinyl nitrogen atom, and one chloride
formed the coordination environment about the Zn(II) center with
a non-ligated counter-anion being present to balance the charge.
The obvious conclusion from these calculations is, given a pseu-
do-trigonal bipyramidal coordination environment with this ligand
system, the NNN-bound system is more stable than one in which
3.3.3. Cyclic voltammetry results and comparison with GAUSSIAN 03-
calculated oxidation potentials
Compound 8 was studied by cyclic voltammetry in DMSO as
part of its characterization. The cyclic voltammogram for 8
(Fig. 8) shows oxidation features at 706, 1018, and 1311 mV, and
reduction waves at ꢀ2336 and ꢀ786 mV. The oxidation and reduc-
tion waves are broad and located at the same potential across con-
secutive scans. This profile is considerably more complex than
what we have observed in previous reports [16,17]. To gain some
Fig. 8. Cyclic voltammogram of 8 in DMSO (5.6 mM) with 0.2 M TBAF. The scan rate was 100 mV/s with ferrocene (E1/2 = 400 mV) used as an internal standard.

J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
319
insight into this electrochemical feature, we chose to perform
quantum mechanical calculations using GAUSSIAN 03.
the intermolecular formation of disulfide bonds, promoted by the
trans positioning of the thionyl S atoms and resulting in more ex-
tended structures that undergo further redox activity as exempli-
fied by the complex cyclic voltammogram reported here.
Unlike in our previous reports, the GAUSSIAN calculations per-
formed as part of this study do not agree well with the experimen-
tally observed oxidation and reduction potentials for the pincer
ligand precursor. In those systems, the oxidations were well-be-
haved and indicative of simple and reversible single oxidations.
As such, the oxidation potentials that we calculated using a sol-
3.4. Reactivity
vated model and a
with those that were determined experimentally. We did note in
our study of the methylene-linked bis(triazolyl)pyridine system
D
G method within GAUSSIAN 03 compared well
Having established a synthetic protocol for this coordination
compound and gained an understanding of its structural character-
istics, we turned our attention to probing its stoichiometric activ-
ity. Compound 9 was screened for activity through the reduction
of 4-nitrobenzaldehyde and pyridine-2-carboxaldehyde, both elec-
tron-poor aldehydes, in the presence of the hydrogen donor, 1-
benzyl-1,4-dihydronicotinamide (BNAH) (Eqs. (2) and (3)). BNAH
was prepared following a known literature procedure and is the re-
agent of choice to model NADH [23].
[
17] that it was necessary to configure the two triazolyl moieties
such that they were stacked to allow the thionyl S atoms to inter-
act intramolecularly upon oxidation as has been observed for simi-
lar systems that are known to form disulfides upon oxidation [41].
Doing so allowed us to compute an oxidation potential that com-
pared well with what we observed experimentally.
ð2Þ
ð3Þ
In our current study, however, the triazolyl rings cannot stack
due to the lack of a CH linker between the pyridinyl and triazolyl
2
rings. As a result, we computed similar oxidation potentials under
each of the three point groups with which we have treated the li-
We have previously reported models for LADH that were
screened for activity for the reduction of electron-poor aldehydes
using BNAH as a hydrogen atom donor to mimic NADH [16,17].
1
For the reduction of 4-nitrobenzaldehyde, H NMR spectroscopy
gand set: 1743 mV (C
these is particularly close to that observed experimentally (ca.
00–1300 mV). However, given our current computational finding
that the most stable conformation of the methyl-substituted ver-
sion of 8 places the thionyl S atoms trans to the pyridinyl N atom
and our previous conclusion that oxidation of a similar species re-
sults in at least the partial formation of a disulfide bond, we sus-
pect that a simple, reversible, one-electron redox process is not
occurring. Rather, electrochemical oxidation of 8 may give rise to
2
), 1701 mV (C
s
), and 1789 mV (C2v). None of
was used to follow the disappearance of the aldehyde proton (d
10.2 ppm) and the shifting of the aromatic CAH protons in the
alcohol product (d 8.24 ppm). The resonances of the carbon-bound
protons in the alcohol product were spectroscopically distinct from
those of the starting materials and no overlap of resonances was
7
observed. For the reduction of pyridine-2-carboxyaldehyde, 1
H
NMR spectroscopy was used to follow the disappearance of the
aldehyde proton (d 10.2 ppm) and the appearance of the aromatic
CAH protons in the alcohol product (d 8.4 ppm).

3
20
J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
Table 3
Stoichiometric reactivity data for the reduction of 4-nitrobenzaldehyde and pyridine-2-carboxaldehyde by ligand precursor 8 or zinc complex 9.
Entry
Substrate
Zn complex or ligand precursor
Time
Conversion (%)
1
2
3
4
5
6
7
8
4-Nitrobenzaldehyde
Pyridine-2-carboxaldehyde
4-Nitrobenzaldehyde
Pyridine-2-carboxaldehyde
4-Nitrobenzaldehyde
Pyridine-2-carboxaldehyde
4-Nitrobenzaldehyde
none
none
8
20 h
20 h
20 h
20 h
20 h
20 h
20 h
20 h
<5
<5
<5
<5
13
13
35
8
ZnCl
ZnCl
9
2
2
Pyridine-2-carboxaldehyde
9
quantitative
Conditions: 0.1 mmol aldehyde, 0.2 mmol BNAH, 0.1 mmol 9 or 0.1 mmol ZnCl
2 3
, and 3 mL CDCl .
For all reactivity experiments, 0.1 mmol of aldehyde, 0.1 mmol
zinc pincer complex possesses a pseudo-trigonal bipyramidal
geometry about the metal center and reacts with BNAH to reduce
electron-poor aldehydes. The zinc complex reacts with BNAH to
quantitatively reduce pyridine-2-carboxaldehyde. The zinc com-
plex also reduced 4-nitro-benzaldehyde. Thus, the novel NNN zinc
pincer complex reduced aldehydes like LADH.
DFT calculations were performed to examine the electronic
properties of the ligand precursor and of the bound zinc system
to investigate the nature of the NNN-binding that we have not ob-
served in similar systems. Calculations on the free ligand indicate
that the most stable structures possess the thionyl S atoms in a
trans conformation relative to the pyridinyl N atom. As for the
zinc-bound complex, the NNN-ligated arrangement is more stable
that the SNS-bound configuration, which we believe is a result not
zinc precursor or 0.1 mmol of ZnCl
used. Control reactions with ZnCl
2
, and 0.2 mmol BNAH were
were performed using one
2
equivalent of this salt because complex 9 contains one zinc ion
1
in the complex. Product formation was detected by H NMR spec-
troscopy by comparison with authentic material. In no case was
there any indication of reduction of nitro substituents. Table 3
illustrates the reactivity data for 9 as well as for ZnCl and the li-
2
gand precursor.
As shown in Table 3, zinc complex 9 enhances the rate of the reac-
tion for the reduction of 4-nitrobenzaldehyde or pyridine-2-carbox-
aldehydewhencomparedtothatforeitherZnCl orligandprecursor.
2
Use of complex 9 results in quantitative conversion of pyridine-2-
carboxaldehyde to pyridin-2-ylmethanol. Mechanistically, others
have proposed a hydrogen atom transfer between the cofactor and
the substrate upon coordination to the zinc active site based upon
a previously reported mechanism for LADH offered by Berreau and
co-workers [42]. Reactivity data for zinc complex 9 shown in Table 3
for the reduction of 4-nitrobenzaldehyde is lower than SNS bis-tria-
zole zinc(II) complexes we previously reported [16,17].
only of the preferred orientation of the free ligand but also of
p
conjugation across the rings of the ligand. We also find that our
computed oxidation potentials do not match well with what is ob-
served experimentally, suggesting that the experimental oxidation
does not correspond to a simple one-electron oxidation of the li-
gand precursor without other reactivity occurring. Our results with
complex 9 point to structural features and redox processes that are
interesting when compared to our previous reports of SNS coordi-
nation of pincer ligands. Furthermore, these results shed new light
on the functionality of the LADH active site as studied through the
use of model complexes.
2
Entries 5 and 6 in Table 3 indicate that ZnCl reacts stoichiomet-
rically with electron-poor aldehydes such as 4-nitrobenzaldehyde
or pyridine-2-carboxyaldehyde to yield alcohol product to a small
extent (ca. 13% conversion). We therefore propose that Zn2 acts as
+
2
a Lewis acid catalyst in the reaction where ZnCl is utilized.
As seen in Table 3, enhancement for the reduction of 4-nitro-
benzaldehyde or pyridine-2-carboxaldehyde was observed for
complex 9. Stoichiometric conversion to the alcohol product was
observed for pyridine-2-carboxaldehyde. Pyridine 2-carboxylate
may be a good substrate for reduction by 9 since there may be fas-
ter hydrogen transfer between the co-factor and the substrate,
which is coordinated to the zinc active site. Based on the mecha-
nism proposed by Berreau and co-workers [42], the low activity
of complex 9 for the reduction of 4-nitrobenzaldehyde could be
due to the slow hydrogen transfer between the co-factor and the
substrate, which is coordinated to the zinc active site. More impor-
tantly, the alcohol product may inhibit the reaction. As the alcohol
is formed, it may coordinate to the zinc metal center as the reac-
tion progresses, and thereby hinder the reaction.
Acknowledgements
This work was supported by generous funding from The Fair-
field University Science Institute (JRM), Fairfield University Start-
up Funding (JRM), Fairfield University Research Grants (JRM), an
NTID Faculty Evaluation and Development Grant (MAL), and the
Bard Summer Research Institute (SSJ). JRM would like to thank
Prof. Matthew A. Kubasik, Prof. L. Kraig Steffen, and Prof. Amanda
Harper-Leatherman for helpful suggestions. The authors would like
to thank the anonymous peer reviewers that helped improve this
article.
Appendix A. Supplementary material
Our work with various benzaldehyde substrates shows that the
enzymatic reaction is significantly enhanced in comparison to the
model enzyme complexes we have previously reported [16,17].
This work has been done under optimal enzymatic conditions
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.ica.2012.07.009.
(
phosphate buffer, pH 8.8 and 25 °C), which are different than
the conditions used in our activity assays with metal complexes.
We are currently working with a variety of substrates to probe
the effect of electronic and steric factors in our reactions. These re-
sults will be presented in a forthcoming paper.
References
[
[
1] R.H. Holm, P. Kennepohl, E.I. Solomon, Chem. Rev. 96 (1996) 2239.
2] J.A. Ibers, R.H. Holm, Science 209 (1980) 223.
[3] (a) W.N. Lipscomb, N. Sträter, Chem. Rev. 96 (1996) 2375;
b) E. Kimura, T. Koike, M. Shionoya, Struct. Bond. 89 (1997) 1.
(
[
4] K.K. Kannan, B. Nostrand, K. Fridborg, S. Lovgren, A. Ohlsson, M. Petef, Proc.
Natl. Acad. Sci. USA 72 (1975) 51.
4
. Conclusions
[
[
[
5] A. Meibner, W. Haehnel, H. Vahrenkamp, Chem. Eur. J. 3 (1997) 261.
6] A. Doł e˛ ga, Coord. Chem. Rev. 254 (2010) 916.
7] A. Doł e˛ ga, A. Pladzyk, K. Baranowska, J. Jezierska, Inorg. Chim. Acta 362 (2009)
5085.
A novel Zn(II) complex containing the NNN coordination of a
tridentate pincer ligand was prepared and characterized. This

J.R. Miecznikowski et al. / Inorganica Chimica Acta 394 (2013) 310–321
321
[
[
8] L. Cronin, P.H. Walton, Chem. Commun. (2003) 1572.
9] L.M. Berreau, M.M. Makowska-Grzyska, A.M. Arif, Inorg. Chem. 40 (2001) 2212.
[23] J. Lutz, F. Hollmann, T.V. Ho, A. Schnyder, R. Fish, A. Schmid, J. Organomet.
Chem. 689 (2004) 4783.
[
[
10] R.M. Kellogg, R.P. Hof, J. Chem. Soc., Perkin Trans. 1 (1996) 1651.
11] S.C. Shoner, K.J. Humphreys, D. Barnhart, J.A. Kovacs, Inorg. Chem. 34 (1995)
[24] Oxford Diffraction, CrysAlis PRO and CrysAlis RED, Oxford Diffraction Ltd.,
Abingdon, Oxfordshire, England, 2010.
5
933.
12] (a) B. Kaptein, G. Barf, R.M. Kellogg, F. Van Bolhuis, J. Org. Chem. 55 (1990)
890;
b) B. Kaptein, L. Wang-Griffen, G. Bart, R.M. Kellogg, J. Chem. Soc., Chem.
[25] G.M. Sheldrick, Acta Crystallogr. A64 (2008) 112.
[
[26] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega,
G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda,
J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene,
X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli,
J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg,
V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick,
A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul,
S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz,
I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng,
A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen,
M.W. Wong, C. Gonzalez, J.A. Pople, GAUSSIAN 03, Revision E.01. Gaussian, Inc.,
Wallingford, CT, 2004.
1
(
Commun. (1987) 1457.
[
[
13] D.T. Corwin, R. Fikar, S.A. Koch, Inorg. Chem. 26 (1987) 3079.
14] (a) C. Kimblin, T. Hascall, G. Parkin, Inorg. Chem. 36 (1997) 5680;
(
(
b) C. Kimblin, B.M. Bridgewater, D.G. Churchill, G. Parkin, Chem. Commun.
1999) 2301.
[
[
15] (a) R. Walz, H. Vahrenkamp, Inorg. Chim. Acta 314 (2001) 58;
b) Y.H. Zhang, H. Vahrenkamp, Inorg. Chim. Acta 351 (2003) 201.
(
16] J.R. Miecznikowski, W. Lo, M.A. Lynn, B.E. O’Loughlin, A.P. DiMarzio, A.M.
Martinez, L. Lampe, K.M. Foley, L.C. Keilich, G.P. Lisi, D.J. Kwiecien, C.M. Pires,
W.J. Kelly, N.F. Kloczko, K.N. Morio, Inorg. Chim. Acta 376 (2011) 515.
17] J.R. Miecznikowski, W. Lo, M.A. Lynn, S. Jain, L.C. Keilich, N.F. Kloczko, B.E.
O’Loughlin, A.P. DiMarzio, K.M. Foley, G.P. Lisi, D.J. Kwiecien, E.B. Butrick, E.
Powers, R. Al-Abbasee, Inorg. Chim. Acta 387 (2012) 25.
[
[27] (a) W.R. Fawcett, Langmuir 24 (2008) 9868;
[
[
[
18] (a) M. Albrecht, G. van Koten, Angew. Chem., Int. Ed. 40 (2001) 3750;
(b) L.E. Roy, E. Jakubikova, G. Guthrie, E.R. Batista, J. Phys. Chem. A 113 (2009)
6745.
[28] M. Albrecht, J.R. Miecznikowski, A. Samuel, J.W. Faller, R.H. Crabtree,
Organomet 21 (17) (2002) 3596.
(
b) A.T. Normand, K.J. Cavell, Eur. J. Inorg. Chem. (2008) 2781.
19] D. Morales-Morales, C.M. Jensen (Eds.), The Chemistry of Pincer Compounds,
Elsevier, New York, 2007.
20] (a) C. Kimblin, T. Hascall, G. Parkin, Inorg. Chem. 36 (1997) 5680;
[29] R.R. Holmes, Progress Inorg. Chem. 32 (1984) 119.
(
(
(
(
b) C. Kimblin, B.M. Bridgewater, D.G. Churchill, G. Parkin, Chem. Commun.
1999) 2301;
c) C. Bergquist, G. Parkin, Inorg. Chem. 38 (1999) 422;
d) G. Parkin, Chem. Rev. 104 (2004) 699;
[30] Y. Kim, S.-J. Kim, A.J. Lough, Polyhedron 20 (2001) 3073.
[31] S.-W. Liang, M.-X. Li, M. Shao, H.-J. Liu, Inorg. Chem. Commun. 10 (2007)
1347.
[32] S.J. Hong, J.S. Seo, J.Y. Ryu, J.H. Lee, C. Kim, S.-J. Kim, Y. Kim, A.J. Lough, J. Mol.
Struct. 751 (2005) 22.
[33] K.T. Youm, J. Ko, M.-J. Jun, Polyhedron 25 (2006) 2717.
[34] J.Y. Ryu, J.H. Han, J.Y. Lee, S.J. Hong, S.H. Choi, C. Kim, S.-J. Kim, S. Kim, Inorg.
Chim. Acta 358 (2005) 3659.
B.M. Bridgewater, T. Fillebeen, R.A. Friesner, G. Parkin, J. Chem. Soc., Dalton
Trans. (2000) 4494.;
(
(
f) J.G. Melnick, A. Docrat, G. Parkin, Chem. Commun. (2004) 2870;
g) C. Kimblin, B.M. Bridgewater, D.G. Churchill, T. Hascall, G. Parkin, Inorg.
Chem. 39 (2000) 4240.
21] (a) M. Tessmer, M. Shu, H. Vahrenkamp, Inorg. Chem. 40 (2001) 4022;
[35] J.Y. Ryu, J.Y. Lee, S.H. Choi, S.J. Hong, C. Kim, Y. Kim, S.-J. Kim, Inorg. Chim. Acta
358 (2005) 3398.
[
(
(
(
(
(
b) J. Seebacher, M. Shu, H. Vahrenkamp, Chem. Commun. (2001) 1026;
c) Y.H. Zhang, H. Vahrenkamp, Inorg. Chim. Acta 351 (2003) 201;
d) M.M. Ibrahim, M. Shu, H. Vahrenkamp, Eur. J. Inorg. Chem. (2005) 1388;
e) R. Walz, H. Vahrenkamp, Inorg. Chim. Acta 314 (2001) 58;
[36] B.V. Trzhtsinskaya, N.D. Abramova, J. Sulfur Chem. 10 (4) (1991) 389.
[37] S.K. Padhi, R. Sahu, V. Manivannan, Polyhedron 27 (2008) 805.
[38] U. Hartmann, H. Vahrenkamp, Inorg. Chim. Acta 239 (1995) 13.
[39] A. Marzotto, D.A. Clemente, G. Valle, Acta Cryst. C50 (1994) 1451.
[40] J.A. Loch, M. Albrecht, E. Peris, J. Mata, J.W. Faller, R.H. Crabtree, Organomet 21
(2002) 700.
f) M. Rombach, J. Seebacher, M. Ji, G. Zhang, G. He, M. Ibrahim, B. Benkmil, H.
Vahrenkamp, Inorg. Chem. 45 (2006) 4571;
(
(
g) M. Ibrahim, J. Seebacher, G. Steinfeld, H. Vahrenkamp, Inorg. Chem. 44
2005) 8531.
[41] A. Suszka, Pol. J. Chem. 54 (1980) 2289.
[42] M.M. Makowska-Grzyska, P.C. Jeppson, R.A. Allred, A.M. Arif, L.M. Berreau,
Inorg. Chem. 41 (2002) 4872.
[
22] C.W. Glynn, M.M. Turnbull, Inorg. Chim. Acta 332 (2002) 92.