O2-dependent aliphatic carbon-carbon bond cleavage reactivity in a Ni(II) enolate complex having a hydrogen bond donor microenvironment; comparison with a hydrophobic analogue

Article abstract of DOI:10.1021/ic901981y

A mononuclear Ni(II) complex having an acireductone type ligand, and supported by the bnpapa (N,N-bis((6-neopentylamino-2-pyhdyl)methyl)-N-((2- pyridyl)methyl)amine) ligand, [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO₄ (14), has been prepared and characterized by elemental analysis, ¹H NMR, FTIR, and UV-vis. To gain insight into the¹H NMR features of 14, the air stable analogue complexes [(bnpapa)Ni(CH₃C(O)CHC(O)CH ₃)]ClO₄ (16) and [(bnpapa)Ni(ONHC(O)CH₃)] ClO₄ (17) were prepared and characterized by X-ray crystallography, ¹H NMR, FTIR, UV - vis, mass spectrometry, and solution conductivity measurements. Compounds 16 and 17 are 1:1 electrolyte species in CH ₃CN. ¹H and ²H NMR studies of 14, 16, and 17 and deuterated analogues revealed that the complexes having six-membered chelate rings for the exogenous ligand (14 and 16) do not have a plane of symmetry within the solvated cation and thus exhibit more complicated 1H NMR spectra. Compound 17, as well as other simple Ni(II) complexes of the bnpapa ligand (e.g., [(bnpapa)Ni(ClO₄)(CH₃CN)]ClO₄ (18) and [(bnpapaNi)₂(μ-Cl)₂](ClO₄)₂ (19)), exhibit ¹H NMR spectra consistent with the presence of a plane of symmetry within the cation. Treatment of [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)] ClO₄ (14) with O₂ results in aliphatic carbon-carbon bond cleavage within the acireductone-type ligand and the formation of [(bnpapa)Ni(O₂CPh)]ClO₄ (9), benzoic acid, benzil, and CO. Use of ¹⁸O₂ in the reaction gives high levels of incorporation (>80%) of one labeled oxygen atom into 9 and benzoic acid. The product mixture and level of ¹⁸O incorporation in this reaction is different than that exhibited by the analogue supported the hydrophobic 6-Ph₂TPA ligand, [(6-Ph₂TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO ₄ (2). We propose that this difference is due to variations in the reactivity of bnpapa- and 6-Ph₂TPA-ligated Ni(II) complexes with triketone and/or peroxide species produced in the reaction pathway.

Full text of DOI:10.1021/ic901981y

Inorg. Chem. 2010, 49, 1071–1081 1071
DOI: 10.1021/ic901981y
O2-Dependent Aliphatic Carbon-Carbon Bond Cleavage Reactivity in a Ni(II)
Enolate Complex Having a Hydrogen Bond Donor Microenvironment; Comparison
with a Hydrophobic Analogue
Katarzyna Grubel,† Amy L. Fuller,† Bonnie M. Chambers,† Atta M. Arif,‡ and Lisa M. Berreau*,†
†Department of Chemistry & Biochemistry, Utah State University, Logan, Utah 84322-0300 and ‡Department of
Chemistry, University of Utah, Salt Lake City, Utah 84112-0850
Received October 7, 2009
A mononuclear Ni(II) complex having an acireductone type ligand, and supported by the bnpapa (N,N-bis((6-
neopentylamino-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine) ligand, [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4
1
(14), has been prepared and characterized by elemental analysis, H NMR, FTIR, and UV-vis. To gain insight
into the 1H NMR features of 14, the air stable analogue complexes [(bnpapa)Ni(CH3C(O)CHC(O)CH3)]ClO4 (16) and
[(bnpapa)Ni(ONHC(O)CH3)]ClO4 (17) were prepared and characterized by X-ray crystallography, 1H NMR, FTIR,
UV-vis, mass spectrometry, and solution conductivity measurements. Compounds 16 and 17 are 1:1 electrolyte
species in CH3CN. 1H and 2H NMR studies of 14, 16, and 17 and deuterated analogues revealed that the complexes
having six-membered chelate rings for the exogenous ligand (14 and 16) do not have a plane of symmetry within the
1
solvated cation and thus exhibit more complicated H NMR spectra. Compound 17, as well as other simple Ni(II)
complexes of the bnpapa ligand (e.g., [(bnpapa)Ni(ClO4)(CH3CN)]ClO4 (18) and [(bnpapaNi)2(μ-Cl)2](ClO4)2 (19)),
exhibit H NMR spectra consistent with the presence of a plane of symmetry within the cation. Treatment of
1
[(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14) with O2 results in aliphatic carbon-carbon bond cleavage within the
acireductone-type ligand and the formation of [(bnpapa)Ni(O2CPh)]ClO4 (9), benzoic acid, benzil, and CO. Use of
18O2 in the reaction gives high levels of incorporation (>80%) of one labeled oxygen atom into 9 and benzoic acid. The
product mixture and level of 18O incorporation in this reaction is different than that exhibited by the analogue supported
the hydrophobic 6-Ph2TPA ligand, [(6-Ph2TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (2). We propose that this difference
is due to variations in the reactivity of bnpapa- and 6-Ph2TPA-ligated Ni(II) complexes with triketone and/or peroxide
species produced in the reaction pathway.
Introduction
six-membered chelate ring in the enzyme substrate adduct
(Scheme 1(top)).2 Reaction of this adduct with O2 results in
oxidative cleavage of the C(1)-C(2) and C(2)-C(3) bonds
and the formation of CO and carboxylate products. For
Fe(II)-ARD, a more open active site is suggested to enable
the formation of a five-membered chelate enediolate struc-
ture, within which only C(1)-C(2) bond cleavage occurs
upon reaction with O2 (Scheme 1(bottom)). For both Ni(II)-
ARD and Fe(II)-ARD secondary hydrogen bonding inter-
actions involving an arginine residue are suggested to stabi-
lize enolate/enediolate coordination.1
Interest in reactions of relevance to Ni(II)-ARD also stems
from the fact that carbon monoxide is a molecule of current
interest in biological systems. In humans, CO is primarily
produced via the oxidative breakdown of heme catalyzed
by heme oxygenases.3 While carbon monoxide is typically
viewed as a toxic gas, recent studies have shown that
this small molecule can have beneficial health effects. The
Interest in how the secondary environment of a metal
center influences the reactivity of metal-bound ligands stems
from the possible roles of secondary interactions in metal-
catalyzed reactions in biological systems.1 In the acireduc-
tone dioxygenases Ni(II)-ARD and Fe(II)-ARD, which
contain the same protein component, it is proposed that
differences in the secondary environment surrounding the
divalent metal center influence the coordination mode of the
acireductone substrate and the regioselectivity of the oxida-
tive carbon-carbon bond cleavage reaction.1 Specifically,
in Ni(II)-ARD the positioning of a tryptophan side
chain (W162) is suggested to promote the formation of a
*To whom correspondence should be addressed. E-mail: lisa.berreau@
usu.edu. Phone: (435) 797-1625. Fax: (435) 797-3390.
(1) Pochapsky, T. C.; Ju, T.; Dang, R.; Beaulieu, R.; Pagani, G. M.;
OuYang, B. In Metal Ions in Life Sciences; Sigel, A., Sigel, H., Sigel, R. K. O.,
Eds.; Wiley-VCH: Weinheim, Germany, 2007; pp 473-498.
(2) Ju, T.; Goldsmith, R. B.; Chai, S. C.; Maroney, M. J.; Pochapsky, S.
S.; Pochapsky, T. C. J. Mol. Biol. 2006, 393, 823–834.
(3) Mann, B. E.; Motterlini, R. Chem. Commun. 2007, 4197–4208.
r
2009 American Chemical Society
Published on Web 12/29/2009
pubs.acs.org/IC

1072 Inorganic Chemistry, Vol. 49, No. 3, 2010
Grubel et al.
Scheme 1
signaling mechanism of CO is similar to that of NO in that it
activates soluble guanylyl cyclase to produce cyclic guanylyl
monophosphate (cGMP).3 This compound is involved in
pathways pertinent to smooth muscle relaxation, platelet
inhibition, and cell growth and differentiation. As these
factors are related to several diseases, recent studies have
focused on efforts toward the development of CO-releasing
compounds for use as therapeutic agents.4 The majority of
the chemical compounds tested so far have been transition
metal carbonyl species,5 although a main group CO-releasing
compound (Na2[H3BCO2]) has been recently reported.4 We
are interested in the CO release properties of acireductones
and flavonolates, both of which possess three consecutive
carbon centers having an oxygen substitutent. In fungal and
bacterial systems, quercetin dioxygenases catalyze CO release
from a metal-coordinated flavonolate in a 2,4-dioxygenolytic
ring cleavage reaction.6-14 In a broad sense, we are interested
in understanding in detail the chemical factors that modulate
the CO-release reactivity of metal-coordinated acireductone
and flavonolate species, with a long-term goal of producing
new types of CO-releasing compounds containing these novel
structural motifs.
Figure 1. Supporting chelate ligands used to isolate Ni(II) enediolate
(top) and enolate (bottom) complexes of relevance to Ni(II)-ARD.
carboxylate-bound forms of Ni(II)-ARD.15-18 We recently
reported that use of a chelate ligand having a mixed hydro-
phobic/hydrogen bond donor secondary environment pro-
duced the first example of a Ni(II) enediolate complex of an
acireductone-type ligand (1, Figure 1(top)).18 Somewhat
surprisingly, this complex was originally generated under
similar conditions to those used to produce the mononuclear
Ni(II) enolate complex [(6-Ph2TPA)Ni(PhC(O)C(OH)C(O)-
Ph)]ClO4 (2, Figure 1(bottom)). These combined results
indicate that the presence of a hydrogen bond donor in the
secondary environment influences the coordination chemis-
try of an acireductone-type ligand.
Our laboratory has reported the only examples to date of
synthetic complexes of relevance to substrate- and product
(4) Motterlini, R.; Sawle, P.; Hammad, J.; Bains, S.; Alberto, R.; Foresti,
R.; Green, C. J. FASEB J. 2005, 19, 284–286.
(5) Zhang, W.-Q.; Atkin, A. J.; Thatcher, R. J.; Whitwood, A. C.;
Fairlamb, I. J. S.; Lynam, J. M. Dalton Trans. 2009, 4351–4358 and references
cited therein.
(6) Oka, T.; Simpson, F. J. Biochem. Biophys. Res. Commun. 1971, 43, 1–5.
(7) Oka, T.; Simpson, F. J.; Krishnamurty, H. G. Can. J. Microbiol. 1972,
18, 493–508.
(8) Hund, H. K.; Breuer, J.; Lingens, F.; Huttermann, J.; Kappl, R.;
Fetzner, S. Eur. J. Biochem. 1999, 263, 871–878.
(9) Tranchimand, S.; Ertel, G.; Gaydou, V.; Gaudin, C.; Tron, T.;
Iacazio, G. Biochemie 2008, 90, 781–789.
(10) Kooter, I. M.; Steiner, R. A.; Dijkstra, B. W.; van Noort, P. I.;
Egmond, M. R.; Huber, M. Eur. J. Biochem. 2002, 269, 2971–2979.
(11) Fusetti, F.; Schroter, K. H.; Steiner, R. A.; van Noort, P. I.; Pijning,
T.; Rozeboom, H. J.; Kalk, K. H.; Egmond, M. R.; Dijkstra, B. W. Structure
2002, 10, 259–268.
In terms of carboxylate chemistry, we discovered that the
secondary environment of the chelate ligand affects the
coordination chemistry of Ni(II)-carboxylate species that
are generated in O2-dependent ARD-type reactions. As
shown in Scheme 2(top), a Ni(II)-carboxylate ligand in a
(15) Szajna, E.; Arif, A. M.; Berreau, L. M. J. Am. Chem. Soc. 2005, 127,
17186–17187.
(12) Gopal, B.; Madan, L. L.; Betz, S. F.; Kossiakoff, A. A. Biochemistry
2005, 44, 193–201.
(13) Schaab, M. R.; Barney, B. M.; Francisco, W. A. Biochemistry 2006,
45, 1035–1042.
(16) Szajna-Fuller, E.; Rudzka, K.; Arif, A. M.; Berreau, L. M. Inorg.
Chem. 2007, 46, 5499–5507.
(17) Szajna-Fuller, E.; Chambers, B. M.; Arif, A. M.; Berreau, L. M.
Inorg. Chem. 2007, 46, 5486–5498.
(14) Merkens, H.; Kappl, R.; Jakob, R. P.; Schmid, F. X.; Fetzner, S.
Biochemistry 2008, 47, 12185–12196.
(18) Rudzka, K.; Arif, A. M.; Berreau, L. M. Inorg. Chem. 2008, 47,
10832–10840.

Article
Inorganic Chemistry, Vol. 49, No. 3, 2010 1073
Scheme 2
responsible for the differences in O2 reactivity between
[(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14) and [(6-Ph2-
TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (2) noted above.
Experimental Section
General Methods. All reagents and solvents were obtained
from commercial sources and were used as received unless
otherwise noted. Solvents were dried according to published
procedures and were distilled under N2 prior to use.19 Air
sensitive reactions were performed in the MBraun Unilab glove-
box or a Vacuum Atmospheres MO-20 glovebox under a N2
atmosphere. The ligand bnpapa and the Ni(II) complex [(6-
Ph2TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (2) were prepared ac-
cording to literature procedures.15,17
Physical Methods. 1H NMR spectra of Ni(II) complexes were
obtained using a Bruker ARX-400 spectrometer as previously
described.20 Chemical shifts (in ppm) are referenced to the
residual solvent peak(s) in CHD2CN (1H, 1.94 (quintet) ppm).
UV-vis spectra were collected on a HP8453A spectrometer at
ambient temperature. FTIR spectra were recorded on a Shi-
madzu FTIR-8400 spectrometer as KBr pellets. Conductance
measurements were made at 22(1) °C using an YSI model 31A
conductivity bridge with a cell having a cell constant of 1.0 cm-1
and using Me4NClO4 as a 1:1 electrolyte standard. Preparation
of the acetonitrile and standard solutions for conductance
measurements and subsequent data analysis were performed
as previously described.21 Mass spectrometry data was obtained
at the Mass Spectrometry Facility, Department of Chemistry,
University of California, Riverside. Elemental analyses were
performed by Atlantic Microlabs, Inc., Norcross, Georgia, or
Canadian Microanalytical Service, Inc., British Columbia.
Caution! Perchlorate salts of metal complexes with organic
ligands are potentially explosive. Only small amounts of material
should be prepared, and these should be handled with great care.22
[(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14). Under a N2
atmosphere, equimolar amounts of bnpapa (0.273 mmol) and
hydrophobic microenvironment undergoes a shift from bi-
dentate to monodentate in the presence of water (conversion
of compounds 3-5 to 6-8).17 No evidence was found for this
type of carboxylate shift chemistry in bnpapa-ligated Ni(II)
carboxylate complexes (9-11, Scheme 2 (bottom)). In these
analogues, the hydrogen bond donor appendages interact
with one oxygen atom of the bidentate carboxylate. In a
Ni(II) benzoate complex supported by a chelate ligand con-
taining both hydrophobic phenyl appendages and a hydro-
gen bond donor, [(6-NA-6-Ph2TPA)Ni(O2CPh)(H2O)]ClO4
(12), a bidentate coordinated carboxylate ligand was also
identified.18
Ni(ClO4)2 6H2O (0.273 mmol) were mixed in acetonitrile and
stirred until the ligand had fully dissolved. Me4NOH 5H2O
3
3
From our initial studies, it is clear that the ligand environ-
ment of a Ni(II) center influences the chemistry of an
acireductone-type ligand. In the studies outlined herein, we
have further evaluated the influence of the chelate ligand
environment by preparing and characterizing the enolate
complex [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14) as
an analogue to the 6-Ph2TPA-supported 2 (Figure 1). Com-
(0.301 mmol) was then added to the mixture, which was stirred
for additional 15 min, resulting in a dark green solution. The
solution was added to solid 2-hydroxy-1,3-diphenylpropan-1,3-
dione23 (0.301 mmol), and the mixture was stirred for 4 h,
yielding a very dark orange/red solution. The solvent was then
removed under reduced pressure. The solid was dissolved in
CH2Cl2, and the solution was filtered through a Celite plug. The
filtrate was concentrated and brought to dryness under vacuum,
leaving a dark orange/red solid, which was washed with Et2O
and dried under vacuum. Yield: 83%. Anal. Calcd for
C43H51N6O7ClNi: C, 60.19; H, 5.99; N, 9.79. Found: C, 60.52;
H, 5.88; N, 9.57. UV-vis [CH3CN, nm (ε, M-1 cm-1)]
393(10,000); FTIR: (KBr, cm-1) 3420 (br s, νNH), 1094
(νClO4), 621 (νClO4).
1
plex 14 has been characterized by elemental analysis, H
NMR, FTIR, and UV-vis. Comparative O2 reactivity
studies for 2 and 14 have been performed under conditions
wherein the inorganic and organic byproducts were identi-
fied. Interestingly, these reactions differ in the specific mix-
ture of products that is generated and in the level of 18O
incorporation in the benzoate/benzoic acid products. We
propose that these differences are due to variations in the
reactivity of bnpapa- and 6-Ph2TPA ligated Ni(II) complexes
with triketone and peroxide/hydroperoxide species produced
in the reaction pathway.
In the course of this research, as a means of gaining
additional insight in the spectroscopic and solution proper-
ties of [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14), we
have also prepared and characterized mononuclear bnpa-
pa-supported Ni(II) acetoacetonato and hydroxamato com-
plexes, as well as perchlorate and chloro derivatives. Prepa-
ration of this family of complexes has enabled a structural
comparison with a similar family of 6-Ph2TPA-supported
mononuclear Ni(II) complexes. This comparison has
provided insight into the structural factors that may be
[(bnpapa)Ni(CH3C(O)CHC(O)CH3)]ClO4 (16). A solution
of Ni(ClO4)2 6H2O (0.15 mmol) in CH3CN (∼1 mL) was added
3
to solid bnpapa (0.15 mmol). The resulting mixture was stirred
for 20 min at room temperature. The solution was then trans-
ferred to a vial containing Me4NOH 5H2O (0.15 mmol). To this
3
mixture 2,4-pentanedione (0.15 mmol) was added, and the
resulting solution was stirred overnight. The solvent was then
removed under reduced pressure. The remaining solid was
(19) Armarego, W. L. F; Perrin, D. D. Purification of Laboratory
Chemicals, 4th ed.; Butterworth-Heinemann: Boston, MA, 1996.
(20) Szajna, E.; Dobrowolski, P. D.; Fuller, A. L.; Berreau, L. M. Inorg.
Chem. 2004, 43, 3988–3997.
(21) Allred, R. A.; McAlexander, L. H.; Arif, A. M.; Berreau, L. M. Inorg.
Chem. 2002, 41, 6790–6801.
(22) Wolsey, W. C. J. Chem. Educ. 1973, 50, A335–A337.
(23) Plietker, B. J. Org. Chem. 2004, 69, 8287–8296.

1074 Inorganic Chemistry, Vol. 49, No. 3, 2010
Grubel et al.
dissolved in CH2Cl2 (∼5 mL), and the solution was filtered
through a Celite/glass wool plug. Pentane diffusion into CH2Cl2
yielded purple crystals suitable for X-ray crystallography. The
crystals were crushed and dried under vacuum prior to elemental
analysis. Yield: 46%. Anal. Calcd for C33H47ClN6NiO6: C,
55.21; H, 6.60; N, 11.71. Found: C, 55.28; H, 6.55; N, 11.70.
FTIR (KBr, cm-1) ∼3300 (s, νNH), 1089 (νClO4), 622 (νClO4).
UV-vis [CH3CN, nm (ε, M-1 cm-1)] 244(31600), 305(17800),
543(sh), 966(19); FAB-MS [m/z (relative intensity)]: 617 ([M -
ClO4]þ, 100%).
from deep orange/red to pale yellow. CO production was
verified by the PdCl2 method.24 The solvent was removed under
reduced pressure, and the resulting solid was dissolved in
hexanes/ethyl acetate (4:1), and the solution was passed through
a silica plug. This produced a yellow filtrate containing the
organic products from the reaction. Ni(II) complexes that
adhered to the silica gel were then eluted using acetonitrile,
1
followed by methanol. As determined by TLC, H NMR, and
GC-MS, the organic fraction contained primarily benzoic acid
(11 mg overall yield - 91% based on production of 1 equiv of
free benzoic acid per enolate ligand; sample is 88-90% benzoic
acid based on 1H NMR), with a small amount of benzil
(PhC(O)C(O)Ph; 10-12%) and a trace amount of the ester
PhC(O)OCH2C(O)Ph present. The ester was identified via
independent synthesis.25 This compound is an isomer of
2-hydroxy-1,3-diphenylpropan-1,3-dione,23 and the reaction
leading to ester formation will be discussed in detail elsewhere.
In each reaction, two Ni(II) complexes were eluted from the
column, [(bnpapa)Ni(O2CPh)]ClO4 (9) and [(bnpapa)Ni(PhC-
(O)C(O)CHC(O)Ph)]ClO4 (15), the latter of which was present
in a very low amount (<5%) and was identified via mass
spectrometry (ESI-MS [m/z (relative intensity)]: 769.3376
(M - ClO4)þ, 100%)). The formation of 15 is related to the
trace ester formation in the reaction and will be discussed in
detail elsewhere. The yield of the metal complexes was ∼88% by
mass following the column (based on stoichiometric formation
of [(bnpapa)Ni(O2CPh)]ClO4 (9)). Thus, from this data, the
formation of [(bnpapa)Ni(O2CPh)]ClO4 (9) was judged as
quantitative. Use of 18O2 in the reaction of 14 with O2 produces
benzoic acid with 81% incorporation of one labeled oxygen
atom. No 18O incorporation was found in benzil or the ester
PhC(O)OCH2C(O)Ph, as determined by GC-MS. Mass spectral
analysis of the metal complexes indicated 87% 18O incorpora-
[(bnpapa)Ni(ONHC(O)CH3)]ClO4 (17). A solution of Ni-
(ClO4)2 6H2O (0.11 mmol) in CH3CN (∼1 mL) was added to
3
solid bnpapa (0.11 mmol). The resulting mixture was stirred for
5 min at the room temperature. The solution was then trans-
ferred to a vial containing Me4NOH 5H2O (0.12 mmol) and
3
acetohydroxamic acid (0.12 mmol), and the resulting solution
was stirred for 1 h. The solvent was then removed under reduced
pressure. The remaining solid was dissolved in CH2Cl2 (∼5 mL),
and the solution was filtered through a Celite/glass wool plug.
Diffusion of diethyl ether into a CH2Cl2/MeOH/iPrOH (1:0.5:1)
solution of the compound yielded purple crystals suitable for
single crystal X-ray crystallography. These crystals were
crushed and dried under vacuum prior to elemental analysis.
Yield: 60%. Anal. Calcd for C30H44N7NiO6Cl 0.25AHA
3
3
0.35CH2Cl2: C, 51.93; H, 6.34; N, 13.12. Found: C, 51.55; H,
6.41; N, 13.63. The presence of acetohydroxamic acid (AHA) in
the crystalline sample was confirmed by X-ray crystallography.
The presence of CH2Cl2 in the elemental analysis sample was
1
confirmed by H NMR. FTIR (KBr, cm-1) ∼3288 (s, νNH),
1103 (νClO4), 621 (νClO4); UV-vis [CH3CN, nm (ε, M-1 cm-1)]
247(25800), 325(10400), 548(sh), 977(32); ESI/APCI-MS [m/z
(relative intensity)]: 592.2914 ([M - ClO4]þ, 100%).
[(bnpapa)Ni(ClO4)(CH3CN)]ClO4 (18). A solution of Ni-
tion into one oxygen atom of the benzoate ligand of 9. No 18
incorporation was found in 15.
O
(ClO4)2 6H2O (0.07 mmol) in CH3CN (∼1 mL) was added to
3
solid bnpapa (0.07 mmol). The resulting mixture was stirred for
20 min at room temperature. The solvent was then removed
under reduced pressure, and the residue was dissolved in
CH2Cl2. Pentane diffusion yielded purple crystals suitable for
X-ray crystallography. The crystals were crushed and dried
under vacuum prior to elemental analysis. Yield: 54%. Anal.
Reanalysis of O2 Reactivity of [(6-Ph2TPA)Ni(PhC(O)C-
(OH)C(O)Ph)]ClO4 (2). Compound 2 was treated with an excess
of O2 in a reaction very similar to that outlined above using 14.
An identical workup procedure was also performed. The or-
ganic products generated were benzoic acid and benzil in a
reproducible ∼75:25 ratio. A trace amount of the ester PhC-
(O)OCH2C(O)Ph is also generated, as determined by GC-MS
Calcd for C30H43Cl2N7NiO8 1/2CH2Cl2: C, 45.69; H, 5.53; N,
3
12.23. Found: C, 45.32; H, 5.60; N, 12.09. UV-vis [CH3CN, nm
1
and H NMR. The total yield of organic products was ∼96%
(ε, M-1 cm-1)] 318(10300), 553(15), 931(17); FTIR (KBr, cm-1
)
based on the proposed formation of 1 equiv of free benzoic acid
per enolate ligand of 2. As previously reported, the Ni(II)
complex [(6-Ph2TPA)Ni(O2Ph)]ClO4 (3) is produced in this
∼3400 (s, νNH), 1103 (νClO4), 624 (νClO4); FAB-MS [m/z (relative
intensity)]: 617 ([M - ClO4 - CH3CN]þ, 100%).
[(bnpapaNi)2(μ-Cl)2](ClO4)2 (19). A solution of Ni(ClO4)2
reaction.16 A trace amount of the enolate complex [(6-Ph2-
3
6H2O (0.14 mmol) in MeOH (∼1 mL) was added to a solution of
bnpapa (0.14 mmol) in MeOH (∼1 mL). The resulting mixture
was stirred for 20 min at room temperature. The solution was
16
TPA)Ni(PhC(O)C(O)CHC(O)Ph)]ClO4
is also generated.
The reaction leading to the formation this complex will be
discussed in detail elsewhere. The total mass of complexes
isolated suggests a ∼70% yield based on the stoichiometric
formation of 3. However, a control experiment using [(6-Ph2-
TPA)Ni(O2Ph)]ClO4 (3) indicated that ∼30% of the material is
lost in the column purification process used to isolate the metal
complexes from the reaction mixture. Thus, the formation of 3 is
nearly quantitative in the O2 reaction of 2. Use of 18O2 in the
reaction produced free benzoic acid with 59% 18O incorporation
in one oxygen atom position, and the benzoate complex 3 having
64% incorporation in one oxygen atom. The level of isotope
incorporation into 3 is slightly higher than that previously
reported (∼50%) based on multiple 18O reactions.16
then transferred to a vial containing Me4NCl 5H2O (0.14
3
mmol) and the resulting mixture was stirred for 1 h. The solvent
was then removed under reduced pressure. The remaining solid
was dissolved in CH2Cl2 (∼5 mL), and the solution was filtered
through a Celite/glass wool plug. Diffusion of diethyl ether into
a CH2Cl2 solution of the compound yielded green crystals
suitable for X-ray crystallography. The crystals were crushed
and dried under vacuum prior to elemental analysis. Yield: 33%.
Anal. Calcd for C28H40Cl2N6NiO4: C, 51.40; H, 6.16; N, 12.84.
Found: C, 51.15; H, 6.29; N, 12.88. FTIR (KBr, cm-1) ∼3340 (s,
ν
NH), 1095 (νClO4), 621 (νClO4); UV-vis [CH3CN, nm (ε, M-1
cm-1)] 325(15900), 600(31), 1032(33); ESI/APCI-MS [m/z
18O2 Reactivity of [Me4N][PhC(O)C(OH)C(O)Ph]. We have
previously reported that treatment of the salt [Me4N][PhC-
(O)C(OH)C(O)Ph] with O2 results in the formation of tetra-
methylammonium benzoate, benzoic acid and CO.16 We have
repeated this reaction using 18O2 and have found by mass
(relative intensity)]: 553.2348 ([M - 2ClO4]2þ, 100%).
O2 Reactivity of 14: Product Isolation and 18O Labeling
Studies. Complex 14 (0.101 mmol) was dissolved in 10 mL of
acetonitrile and O2 was bubbled through the solution for ∼1
min. The reaction was then left stirring overnight at ambient
temperature. Over the course of this time, the color changed
(25) (a) Ming, L.; Guilong, Z.; Lirong, W.; Huazheng, Y. Synth. Commun.
2005, 35, 493–501. (b) Liu, Z.; Chen, Z.-C.; Zheng, Q.-G. Synthesis 2004, 33–36.
(24) Allen, T. H.; Root, W. S. J. Biol. Chem. 1955, 216, 309–317.

Article
Inorganic Chemistry, Vol. 49, No. 3, 2010 1075
spectrometry that the benzoate/benzoic acid contains ∼65%
Scheme 3
18O incorporation when generated from Me4NOH 5H2O and
PhC(O)C(OH)C(O)Ph in dry CH3CN. Pre-drying of the Me4-
3
NOH 5H2O under vacuum for 24 h prior to use in the reaction
produced a slightly higher level of 18O incorporation (72%) in
the benzoate/benzoic acid product.
3
X-ray Crystallography. A single crystal of each compound 16,
17 1/4AHA (AHA = acetohydroxamic acid), 18 CH2Cl2, and
19 2CH2Cl2 was mounted on a glass fiber with traces of viscous
3
3
3
oil and then transferred to a Nonius KappaCCD diffractometer
˚
equipped with Mo KR radiation (λ = 0.71073 A) for data
collection. For unit cell determination, 10 frames of data were
collected at 103(1) K or 150(1) K with an oscillation range of 1
deg/frame and an exposure time of 20 s/frame. Final cell
constants were determined from a set of strong reflections from
the actual data collection. All reflections were indexed, inte-
grated, and corrected for Lorentz polarization and absorption
effects using DENZO-SMN and SCALEPAC.26 The structures
were solved by a combination of direct and heavy-atom methods
using SIR 97. All of the non-hydrogen atoms were refined with
anisotropic displacement coefficients. Unless otherwise stated,
all hydrogen atoms were assigned isotropic displacement coeffi-
cients U(H) = 1.2U(C) or 1.5U(Cmethyl), and their coordinates
were allowed to ride on their respective carbons using
SHELXL97.27 Complex 16 crystallizes in the space group P1,
with two carbon atoms of one neopentyl group exhibiting
disorder over two positions. Complex 17 1/4AHA crystallizes
in the space group C2/c with three oxygen atoms of the
3
perchlorate anion and the carbon atoms of one nepentyl group
exhibiting disorder. Complex 18 CH2Cl2 crystallizes in the
3
space group P21/c. The CH2Cl2 solvate molecule exhibits dis-
order. Complex 19 2CH2Cl2 crystallizes in the space group
3
P21/n, with one CH2Cl2 exhibiting disorder in the position of
one chlorine atom.
Results
Preparation and Characterization of [(bnpapa)Ni-
(PhC(O)C(OH)C(O)Ph)]ClO4 (14). Treatment of the
bnpapa chelate ligand with equimolar amounts of Ni-
(ClO4)2 6H2O, Me4NOH 5H2O, and 2-hydroxy-1,3-di-
Air Stable Analogues. To aid in the interpretation of
the 1H NMR spectroscopic features of 14, air stable
analogue complexes containing a bidentate acetoaceto-
nato ([(bnpapa)Ni(CH3C(O)CHC(O)CH3)]ClO4 (16)) or
hydroxamato ([(bnpapa)Ni(ONHC(O)CH3)]ClO4 (17))
ligand were prepared and comprehensively characterized.
For solution conductivity and spectroscopic studies, the
perchlorate complex [(bnpapa)Ni(ClO4)(CH3CN)]ClO4
(18) and chloride complex [(bnpapaNi)2(μ-Cl)2](ClO4)2
(19) were also prepared and characterized. Drawings of
the cationic portions of these complexes are given in
Scheme 3.
3
3
phenylpropan-1,3-dione in CH3CN, followed by work up
using CH2Cl2, yielded a deep orange/red solid. Unfortu-
nately, repeated attempts to produce crystals of this
complex suitable for single crystal X-ray crystallography
were unsuccessful. Instead, the orange/red solid was
characterized by elemental analysis, UV-vis, FTIR,
1
and H NMR. The elemental analysis data is consistent
with the proposed formulation. The πfπ* transition of
the coordinated enolate ligand of 14 is found at 393 nm
(ε ∼ 10,000 M-1 cm-1). The wavelength and intensity of
this absorption feature is generally similar to that re-
ported for [(6-Ph2TPA)Ni((PhC(O)C(OH)C(O)Ph)]ClO4
(2; λmax = 399 nm (ε ∼ 6,800 M-1 cm-1)).16 A broad
absorption feature at ∼3420 cm-1 in the infrared spec-
trum of 14 is consistent with hydrogen bonding interac-
tions involving the neopentylamine groups of the bnpapa
chelate ligand. On the basis of structural studies of air
stable analogues (vide infra), we propose that this hydro-
gen bonding involves an oxygen atom of the chelating
enolate ligand that is positioned trans to the tertiary
amine nitrogen donor of the chelate ligand.
X-ray Crystallography. The cationic portions of 16 and
17 are shown in Figure 2, and those of 18 and 19 are
shown in Figure 3. Details of the data collection and
refinement are given in Table 1. Selected bond distances
and angles are given in Table 2. The mononuclear 16 and
17 each contain a pseudo-octahedral Ni(II) center with
the oxygen donor atoms of the chelate ligand positioned
trans to N(3) and N(6). The respective Ni-O/N bonds of
the primary coordination sphere are similar in these
complexes, with the most noticeable difference in bond
lengths being that the Ni-N interactions involving the
˚
neopentylamine-appended pyridyl donors are ∼0.02 A
longer in 16 than those found in the hydroxamato com-
plex (17). In terms of bond angles, a more acute O(1)-Ni-
(1)-O(2) angle in 17 (81.86(10)°) than that found in 16
(94.98(3)°) is due to the difference in chelate ring size of
the bidentate O,O-donor ligands. In both complexes, an
(26) Otwinowski, Z.; Minor, W. Methods Enzymol. 1997, 276, 307–
326.
(27) Sheldrick, G. M. SHELXL-97, Program for the Refinement of Crystal
€
€
Structures; University of Gottingen: Gottingen, Germany, 1997.

1076 Inorganic Chemistry, Vol. 49, No. 3, 2010
Grubel et al.
oxygen atom of the bidentate chelate ligand accepts two
hydrogen bonds from the neopentyl amine groups of the
supporting chelate ligand. These interactions are charac-
˚
terized by N(H) O distances of 2.8-2.9 A.
3 3 3
Solution Conductivity Properties. The acetoacetonato
complex 16 and the hydroxamato complex 17 both are 1:1
electrolytes in CH3CN, as determined by variable con-
centration conductance measurements.21 Onsager plots
for these complexes (Figure 4) exhibit slopes similar to the
1:1 standard Me4NClO4, and a notably different slope
than that exhibited by [(bnpapa)Ni(ClO4)(CH3CN)]-
(ClO4)2 (18 (Figure 3(top)) or [(bnpapaNi)2(μ-Cl)2]-
(ClO4)2 (19, Figure 3(bottom)), both of which are 1:2
electrolyte species in CH3CN.
1
1H NMR Spectra. The H NMR features of analyti-
cally pure [(bnpapa)Ni(CH3C(O)CHC(O)CH3)]ClO4
(16) and [(bnpapa)Ni(ONHC(O)CH3)]ClO4 (17) in
CD3CN at 22(1) °C in the region of 20-80 ppm are
shown in Figure 5(b) and (c). These are compared to the
1H NMR spectral features of the O2-sensitive enolate
complex [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14,
Figure 5(a)). The resonances in the 20-80 ppm region
include those of pyridyl β-H ring protons and a portion of
the benzylic proton resonances.20
The 1H NMR spectra of 14 and 16 (Figure 5(a) and (b))
are similar, both having a more complicated appearance
than that of the hydroxamato compound 17. On the basis
of the conductivity data presented above for the air stable
16 and 17, which are both 1:1 electrolyte species in
acetonitrile, the greater complexity of the 1H NMR
spectrum of 16, relative to the spectral features of 17, is
not due to the formation of multinuclear species in
Figure 2. Thermal ellipsoid drawings of the cationic portions of 16
and 17. All ellipsoids are drawn at the 50% probability level. Hydro-
gen atoms, other than the neopentyl amine N-H hydrogen atoms
and the hydroxamato N-H hydrogen in 17, have been omitted for
clarity.
2
solution. H NMR studies of analogues of 14, 16, and
17 supported by a version of the bnpapa chelate ligand
(Supporting Information, Figure S1) having deuterium
atoms at the benzylic positions, as well as partial deutera-
tion of the β-H positions of the neopentylamine-
appended pyridyl rings, indicated the presence of three
unique benzylic proton resonances for 14 and 16 in the
region of 165-175 ppm. This is consistent with no plane
of symmetry within the cation.20 However, 17 exhibits
only one benzylic proton resonance in the same region,
which is consistent with the presence of a plane of
symmetry containing the unsubstituted pyridyl donor
and the hydroxamato ligand. The factors that govern
the subtle differences in solution structure of the cationic
portions of 14, 16, and 17 are not entirely clear, but
appear to relate to the chelate ring size of the O,O-donor
ligand coordinated to the Ni(II) center. Specifically, the
compounds having a six-membered chelate O,O donor
lack a plane of symmetry in the solution form of the
cation. We note that the 1:2 electrolyte compounds
[(bnpapa)Ni(ClO4)(CH3CN)](ClO4)2 (18) or [(bnpapa-
1
Ni)2(μ-Cl)2](ClO4)2 (19) both exhibit H NMR spectra
similar to 17 wherein an effective plane of symmetry
renders the two neopentylamine-appended pyridyl do-
nors equivalent in solution (Supporting Information,
Figure S2). Ni(II) carboxylate complexes of the general
formula [(bnpapa)Ni(O2CR)]ClO4 (R = Ph, (CH2)2-
1
SCH3, and H) also exhibit H NMR spectra that are
Figure 3. Thermal ellipsoid drawings of the cationic portions of 18 and
19. All ellipsoids are drawn at the 50% probability level. Hydrogen atoms
other than the neopentyl amine N-H hydrogen atoms have been omitted
for clarity.
generally similar to the spectrum found for the hydro-
xamato complex 17.17 In terms of comparing chelate
ligand environments, the mononuclear Ni(II) complexes

Article
Inorganic Chemistry, Vol. 49, No. 3, 2010 1077
Table 1. Summary of X-ray Data Collection and Refinementa
16
17 1/4AHA
3
18 CH2Cl2
3
19 2CH2Cl2
3
empirical formula
Mr
C33H47ClN6NiO6
717.93
triclinic
P1
8.9810(2)
10.9647(2)
18.2657(4)
102.6548(12)
96.3498(11)
93.1764(13)
1738.34(6)
2
C30.50H45.25ClN7.25NiO6.5
711.25
monoclinic
C2/c
32.3396(8)
11.4649(3)
19.4692(3)
90
93.1236(14)
90
7207.9(3)
8
1.312
103(1)
purple
C31H45Cl4N7NiO8
844.25
monoclinic
P21/c
8.8221(2)
20.0037(4)
21.7170(4)
90
91.7754(11)
90
3830.66(14)
4
1.464
150(1)
purple
C58H84Cl8N12Ni2O8
1478.39
monoclinic
P21/n
10.9123(2)
18.9857(3)
16.9677(3)
90
96.6495(10)
90
3491.68(10)
2
1.406
crystal system
space group
˚
a/A
˚
b/A
˚
c/A
R/deg
β/deg
γ/deg
3
˚
V/A
Z
Dc/Mg m-3
T/K
color
1.372
150(1)
150(1)
green
purple
0.38 ꢀ 0.30 ꢀ 0.28
crystal size/ mm
μ/ (mm-1
0.20 ꢀ 0.20 ꢀ 0.15
0.38 ꢀ 0.38 ꢀ 0.33
0.38 ꢀ 0.30 ꢀ 0.25
)
0.687
55.00
0.644
55.04
0.842
54.96
0.904
54.96
2θmax (deg)
completeness to θ (%)
reflections collected
independent reflections
Rint
97.9
12170
7825
0.0219
577
0.0491/0.1289
1.043
0.758/-0.778
99.5
15128
8259
0.0401
486
0.0620/0.1452
1.040
0.790/-0.626
99.2
14723
8717
0.0255
469
0.0636/0.1571
1.042
0.783/-1.250
99.8
15105
7984
0.0200
422
0.0432/0.1038
1.081
0.499/-0.530
variable parameters
R1/wR2b
goodness-of-fit (F2)
-3
˚
ΔFmax/min/e A
P
P
P
P
a
Diffractometer: Nonius KappaCCD; radiation used: Mo KR (λ = 0.71073 A). b R1 = ||Fo| - |Fc||/ |Fo|; wR2 = [ w(Fo2 - Fc2)2/ w(Fo2)2]1/2
where w = 1/[σ2(Fo2) þ (aP)2 þ bP].
,
˚
˚
Table 2. Selected Bond Distances (A) and Angles (deg)
16
17 1/4AHA
3
18 CH2Cl2
3
19 2CH2Cl2
3
Ni(1)-O(1)
2.0162(18)
2.0183(17)
2.1509(19)
2.0762(19)
2.154(2)
2.018(2)
2.058(2)
2.137(3)
2.076(3)
2.134(3)
2.048(3)
2.177(2)
Ni(1)-O(2)
Ni(1)-N(2)
2.151(3)
2.055(3)
2.164(3)
2.042(3)
2.049(3)
2.1998(19)
2.0648(19)
2.2267(19)
2.038(2)
Ni(1)-N(3)
Ni(1)-N(4)
Ni(1)-N(6)
2.061(2)
Ni(1)-N(7)
Ni(1)-Cl(1)
2.4284(6)
2.4485(6)
Ni(1)-Cl(1)#1
O(1)-Ni(1)-O(2)
O(1)-Ni(1)-N(6)
O(2)-Ni(1)-N(6)
O(1)-Ni(1)-N(3)
O(2)-Ni(1)-N(3)
N(6)-Ni(1)-N(3)
O(1)-Ni(1)-N(2)
O(2)-Ni(1)-N(2)
N(6)-Ni(1)-N(2)
N(3)-Ni(1)-N(2)
O(1)-Ni(1)-N(4)
O(2)-Ni(1)-N(4)
N(6)-Ni(1)-N(4)
N(3)-Ni(1)-N(4)
N(2)-Ni(1)-N(4)
N(6)-Ni(1)-N(7)
N(7)-Ni(1)-N(3)
N(7)-Ni(1)-N(2)
N(7)-Ni(1)-N(4)
N(7)-Ni(1)-O(1)
N(6)-Ni(1)-Cl(1)
N(3)-Ni(1)-Cl(1)
N(2)-Ni(1)-Cl(1)
N(4)-Ni(1)-Cl(1)
N(6)-Ni(1)-Cl(1)#1
N(3)-Ni(1)-Cl(1)#1
N(2)-Ni(1)-Cl(1)#1
N(4)-Ni(1)-Cl(1)#1
Cl(1)-Ni(1)-Cl(1)#1
Ni(1)-Cl(1)-Ni(1)#1
90.94(8)
172.86(8)
95.76(8)
89.89(8)
178.63(7)
83.46(8)
91.27(7)
99.02(7)
90.13(7)
79.86(7)
88.86(8)
99.99(8)
87.55(8)
81.12(8)
160.98(8)
81.86(10)
94.53(10)
174.68(10)
178.78(10)
99.35(11)
84.26(11)
99.44(11)
89.69(10)
87.04(11)
80.67(11)
100.25(12)
91.27(10)
93.24(11)
79.68(11)
160.22(11)
90.23(12)
176.14(10)
85.97(13)
99.80(10)
85.13(8)
88.72(11)
80.84(11)
98.42(10)
88.00(7)
79.27(7)
89.12(11)
80.84(11)
161.66(11)
179.59(13)
94.09(12)
90.89(11)
91.29(11)
89.71(11)
90.16(7)
79.58(7)
97.34(6)
177.53(6)
100.65(5)
100.48(5)
177.63(6)
93.76(6)
89.74(5)
91.70(5)
83.77(2)
96.23(2)

1078 Inorganic Chemistry, Vol. 49, No. 3, 2010
Grubel et al.
Figure 6. (a) Proposed structure of [(bnpapa)Ni(PhC(O)C(OH)-
C(O)Ph)]ClO4 (14). (b) Structure of [(6-Ph2TPA)Ni(PhC(O)C(OH)C-
(O)Ph)]ClO4 (2) as determined by X-ray crystallography.15
elsewhere. The monobenzoate complex [(bnpapa)Ni-
(O2CPh)]ClO4 (9) is produced in nearly quantitative yield
in the reaction, with a trace amount of a second Ni(II)
complex, [(bnpapa)Ni(PhC(O)C(O)CHC(O)Ph]ClO4 (15),
being identified by mass spectrometry. The production of
15 is related to the presence of the ester PhC(O)OCH2-
C(O)Ph in the reaction and will be discussed elsewhere.
Use of 18O2 in the reaction with 14 produces benzoic acid
with 81% 18O incorporation in one oxygen atom position.
No 18O incorporation was found in benzil or the ester
PhC(O)OCHsC(O)Ph, as determined by GC-MS. Mass
spectral analysis of the Ni(II) products indicated that the
benzoate complex 9 had 87% 18O incorporation in one
oxygen atom of the benzoate ligand. No 18O incorpo-
ration was found in 15. We note that the level of 18O
incorporation for the reaction involving 14 is slightly
higher than that reported for the Ni(II)-ARD enzymatic
reaction (77.5%).28
Figure 4. Onsager plots of the solution conductivity properties of 9,
16-19, and the 1:1 standard Me4NClO4 in CH3CN at 22(1) °C.
Figure 5. 1H NMR spectral features of (a) 14, (b) 16, and (c) 17 in the
region of 20-80 ppm. Spectra obtained in CD3CN at 22(1) °C.
The workup procedure used to isolate the organic and
inorganic products of the reaction of 14 with O2 is slightly
different in terms of solvents used from the procedure that
we previously reported for identification of the products
of the reaction of [(6-Ph2TPA)Ni(PhC(O)C(OH)C-
(O)Ph)]ClO4 (2) with O2.16 The new conditions are more
amenable to the isolation of free benzoic acid in the
reaction mixture. Therefore, the reaction involving 2
was repeated under conditions identical with those em-
ployed for [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4
(14), with the results shown in Scheme 4. CO production
was again identified qualitatively using the PdCl2 met-
hod.24 In this reaction a ∼75:25 mixture of benzoic acid
and benzil is produced, along with a trace amount of the
ester PhC(O)OCH2C(O)Ph. The Ni(II)-containing pro-
ducts are [(6-Ph2TPA)Ni(O2CPh)]ClO4 (3) and a trace
amount of [(6-Ph2TPA)Ni(PhC(O)C(O)CHC(O)Ph)]-
ClO4 (20).16,17 Use of 18O2 in the reaction with 2 yielded
benzoic acid with 59% 18O incorporation in one oxygen
atom position, and the benzoate complex 3 having 64%
incorporation in one oxygen atom. We note that the level
of isotope incorporation in 3 is slightly higher that than
previously reported (∼50%), but is similar to that found
for the O2 reaction of the salt [Me4N][PhC(O)-
C(OH)C(O)Ph], which decomposes upon reaction with
18O2 to give [Me4N][O2CPh] and benzoic acid (∼65%
incorporation of one 18O into carboxylate group) and
CO. Thus, the reaction involving 2 gives a mixture of
[(6-Ph2TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (2) and
[(6-Ph2TPA)Ni(RC(O)CHC(O)R)]ClO4 (R = Ph, CH3)
exhibit spectra which indicate the presence of a plane of
symmetry within the cation.15,16 Thus, the bnpapa-
ligated Ni(II) six-membered ring enolate complexes 14
and 16 exhibit unique solution 1H NMR properties
relative to their hydrophobic analogues.
On the basis of the structural and solution features of
the air stable acetoacetonato complex 16, and the simi-
larity of the H NMR spectrum of this complex to the
1
spectrum of [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4
(14), we propose that the O2-reactive enolate complex
14 has a structure that is similar to the analogue sup-
ported by 6-Ph2TPA (Figure 6), but is distorted such that
no plane of symmetry relates the neopentylamine pyridyl
donors in the solution form of the cation.
Reaction of 14 with O2. Exposure of a CH3CN solution
of 14 to O2 results in an immediate color change from
deep orange/red to yellow. CO production in this reaction
was identified qualitatively using the PdCl2 method.24
The inorganic and organic products of the reaction were
separated by column chromatography and identified
(Scheme 4). One equivalent of benzoic acid is generated
along with a small amount of benzil (PhC(O)C(O)Ph;
ratio of benzoic acid to benzil is ∼90:10) and a trace
amount of the ester PhC(O)OCH2C(O)Ph, the latter of
which was identified via independent synthesis.25 The
reaction leading to ester formation will be described
(28) Wray, J. W.; Abeles, R. H. J. Biol. Chem. 1995, 270, 3147–3153.

Article
Inorganic Chemistry, Vol. 49, No. 3, 2010 1079
Scheme 4. Major Products Identified in Reaction of 14 and 2 with O2; Results of Reactions Performed Using 18O2
Table 3. Structural Properties of bnpapa-Ligated Mononuclear Ni(II) Complexes
a
N(2)-Ni-N(4) (deg)a
Ni-N(2), Ni-N(4) (A)
reference
˚
˚
N(H) N(H) (A)
complex
3 3 3
[(bnpapa)Ni(ClO4)(CH3CN)]ClO4
[(bnpapa)Ni(ONHC(O)CH3)]ClO4
[(bnpapa)Ni(CH3C(O)CHC(O)CH3)]ClO4
161.66(11)
160.22(11)
160.98(8)
161.78(12)
2.151(3), 2.164(3)
2.137(3), 2.134(3)
2.1509(19), 2.154(2)
2.125(3), 2.136(3)
5.7
5.5
5.6
5.6
this work
this work
this work
17
b
[(bnpapa)Ni(O2Ph)]ClO4
a N(2) and N(4) are the neopentylamine-appendedpyridyl donors of the bnpapaligand. b Data reported for one of two crystalline forms of the complex
that were previously reported.
Table 4. Structural Properties of 6-Ph2TPA-Ligated Mononuclear Ni(II) Complexes
a
b
C(Ph)..C(Ph) (A)
N(3)-Ni-N(4) (deg)a
Ni-N(3), Ni-N(4) (A)
reference
˚
˚
complex
[(6-Ph2TPA)Ni(CH3CN)(CH3OH)](ClO4)2
[(6-Ph2TPA)Ni(ONHC(O)CH3)]ClO4
[(6-Ph2TPA)Ni(CH3C(O)CHC(O)CH3)]ClO4
[(6-Ph2TPA)Ni(PhC(O)C(O)CHC(O)Ph)]ClO4
[(6-Ph2TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4
[(6-Ph2TPA)Ni-Cl(CH3CN)]ClO4
158.59(16)
147.19(7)
150.41(8)
158.40(11)
157.04(8)
157.67(10)
149.83(6)
158.28(10)
141.57(10)
159.33(12)
148.73(8)
150.97(7)
158.42(11)
2.218(5), 2.200(5)
2.229(2), 2.263(2)
2.217(2), 2.221(2)
2.209(3), 2.333(3)
2.271(2), 2.323(2)
2.081(3), 2.213(2)
2.1458(16), 2.234(16)
2.216(2), 2.241(2)
2.233(3), 2.193(3)
2.240(3), 2.186(3)
2.198(2), 2.165(2)
2.1884(17), 2.2050(17)
2.194(3), 2.218(3)
6.3
6.4
6.4
6.5
6.6
6.4
6.2
6.4
6.3
6.3
6.3
6.4
6.3
20
20
16
16
15
20
16
17
17
17
17
17
17
[(6-Ph2TPA)Ni(O2CPh)]ClO4
[(6-Ph2TPA)Ni(O2CPh)(H2O)]ClO4
[(6-Ph2TPA)Ni(O2C(CH2)2SCH3)]ClO4
[6-Ph2TPA)Ni(O2(CH2)2SCH3)(H2O)]ClO4
[(6-Ph2TPA)Ni(O2CCH2SCH3)]ClO4
[(6-Ph2TPA)Ni(O2CCH2SCH3)(H2O)]ClO4
[(6-Ph2TPA)Ni(O2CH)(H2O)]ClO4
a N(3) and N(4) are the phenyl-appended pyridyl donors of the 6-Ph2TPA ligand. b Ipso carbon atoms of phenyl appendages.
organic products (benzoic acid and benzil), but with a
similar level of 18O incorporation to that found for the O2
reaction of [Me4N][PhC(O)C(OH)C(O)Ph].
families of complexes. First, the neopentylamine amine-
appended pyridyl donors in the bnpapa ligand, which
have a substituent that is more electron donating and less
sterically demanding relative to the phenyl substitutents
of the 6-Ph2TPA ligand, have slightly shorter Ni-N
Overall, the studies outlined above revealed two inter-
esting differences in the O2 reactivity of [(bnpapa)Ni-
(PhC(O)C(OH)C(O)Ph)]ClO4 (14) and [(6-Ph2TPA)Ni-
(PhC(O)C(OH)C(O)Ph)]ClO4 (2). First, the O2 reaction
involving the bnpapa-ligated complex 14 produces less of
the side product benzil. Second, the reaction involving 14
has a higher level of 18O incorporation in the benzoic
acid/benzoate products. These combined results provide
evidence that the chelate ligand environment is influencing
the aliphatic carbon-carbon bond cleavage reaction
pathway.
Comparison of the Secondary Environments of bnpapa-
and 6-Ph2TPA-Ligated Ni(II) Complexes. To date, we
have structurally characterized 4 bnpapa- and 13 6-Ph2-
TPA-ligated mononuclear Ni(II) complexes. Shown in
Tables 3 and 4 are bond distances and angles involving
the neopentyl-appended pyridyl donors in the bnpapa
complexes and the phenyl-appended pyridyl donors in the
6-Ph2TPA derivatives. Several conclusions can be drawn
from comparison of the microenvironments in these two
˚
distances (overall average of bnpapa complexes 2.14 A;
˚
6-Ph2TPA complexes 2.22 A). There is also a more linear
N-Ni-N bond angle (overall average of bnpapa com-
plexes 161°; 6-Ph2TPA complexes 154°) between the
substituted pyridyl groups. Second, the phenyl-appended
pyridyl donors of 6-Ph2TPA exhibit more variation in
˚
terms of Ni-N distances (∼0.12 A) in response to the
presence of different exogenous ligands. This is not
surprising in that aryl-appended pyridyl donors of chelate
ligands have been shown to fully dissociate from a metal
center in response to exogenous ligand coordination.29
Third, the microenvironment of bnpapa-ligated com-
plexes is more compact, as determined by comparison
of the distance between the two neopentylamine nitrogen
˚
atoms (∼5.6 A) versus that of the ipso carbons of the
˚
phenyl appendages of 6-Ph2TPA (∼6.4 A).
(29) Berreau, L. M. Comm. Inorg. Chem. 2007, 28, 123–171.

1080 Inorganic Chemistry, Vol. 49, No. 3, 2010
Grubel et al.
Scheme 5. Possible Reaction Pathways for Oxidative Carbon-Carbon Bond Cleavage in the Ni(II) Enolate Complexes 2 and 14a
a The supporting chelate ligands have been omitted for clarity.
Discussion
side product benzil was also identified. The yield of this
byproduct is higher in the reaction involving [(6-Ph2TPA)Ni-
(PhC(O)C(OH)C(O)Ph)]ClO4 (2). Notably, this reaction
exhibits a level of 18O incorporation in the benzoate/benzoic
acid products that is ∼20% lower than the reaction involving
14. A possible rationale for the differences in product
distribution and 18O incorporation between the reactions
involving 2 and 14 could be that differing pathways for
carbon-carbon bond cleavage may be operative as outlined
in Scheme 5. Pathway A involves a cyclic peroxide resulting
from two-electron oxidation of the coordinated acireductone
analogue. Carbon-carbon bond cleavage in this type of
structure would produce 2 equiv of benzoate/benzoic acid,
with each product having one labeled oxygen atom if the
reaction were performed using 18O2. The production of
benzoic acid in high yield in the reaction involving
[(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14), and the ob-
served high level of 18O incorporation, suggests that this
pathway could possibly be operative for this reaction. How-
ever, the production of a small amount of benzil in the
reaction involving 14 suggests that another type of reactivity
is also occurring. For both complexes, we propose that benzil
is generated via a pathway B type reaction sequence
(Scheme 5). Specifically, two electron oxidation of the co-
ordinated acireductone type ligand could produce 1,3-diphe-
nyltriketone and a solvated Ni(II) complex of the chelate
ligand. It has been previously shown that 1,3-diphenyltrike-
tonewillundergophenyl or benzoyl migration inthepresence
of Lewis acid such as AlCl3 to give benzil and carbon
monoxide.30 If this type of reaction pathway is occurring
with the complexes described herein, the secondary environ-
ment of the[(bnpapa)Ni(sol)2]2þ and [(6-Ph2TPA)Ni(sol)2]2þ
cations (sol = solvent; e.g., CH3CN) could influence interac-
tions between the Ni(II) center and the1,3-diphenyltriketone.
As shown in Scheme 1, a key issue in the chemistry of
acireductone dioxygenases is how the coordination mode of
the acireductone substrate may influence the reaction with
O2. Pochapsky and co-workers have suggested, on the basis
of NMR experiments, that differences in the secondary
environment in Ni(II)- versus Fe(II)-containing ARD en-
zyme may be responsible for inducing different coordination
modes of the acireductone substrate.1 Specifically, in Ni(II)-
ARD the side chain of a tryptophan residue is positioned
such that the binding pocket for the acireductone is smaller
than that found in Fe(II)-ARD. This is proposed to induce
the formation of a six-membered chelate ring structure,
which leads to 1,3-dioxygenolytic bond cleavage and CO
production. We note that in both Ni(II)- and Fe(II)-contain-
ing acireductone dioxygenases an arginine residue is posi-
tioned within the active site, likely within hydrogen-bonding
distance of the coordinated acireductone.1
As an approach toward evaluating the influence of the
secondary environment on the chemistry of Ni(II) complexes
having an acireductone-type ligand, we have prepared and
characterized [(6-Ph2TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4
(2), which has a hydrophobic microenvironment, and
[(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14), which con-
tains a hydrogen-bond donorsecondary environment. On the
basis of the results of analytical and spectroscopic studies, we
propose that the coordination mode of the acireductone-type
ligand in these complexes is similar, with each having a six-
membered chelate ring. However, the solution structures of 2
and 14 differ in terms of the presence of a plane of symmetry
that relates the modified pyridyl donors, with the hydrogen
bond donor pocket lacking such symmetry. Treatment of
each complex with O2 results in CO production and aliphatic
carbon-carbon bond cleavage, with the major products in
each reaction being a mononuclear Ni(II) benzoate complex,
benzoic acid, and CO. In both reactions, the formation of the
(30) Roberts, J. D.; Smith, D. R.; Lee, C. C. J. Am. Chem. Soc. 1951, 73,
618–625.

Article
Inorganic Chemistry, Vol. 49, No. 3, 2010 1081
For example, the larger pocket for the 6-Ph2TPA-ligated
Ni(II) center could be a key factor in promoting Lewis acid
activation of a carbonyl moiety of the triketone, which is
necessary for the migration reaction leading to benzil pro-
duction.30 This is a possible rationale for the higher amount
of benzil produced in the reaction involving 2. In terms of the
lower level of 18O incorporation found in this reaction,
triketones are known to hydrate easily at the central carbo-
nyl, and this may be a pathway for the introduction of
unlabeled oxygen atoms into the benzoate/benzoic acid
products.31 The observation that the salt [Me4N][PhC(O)-
CH(OH)C(O)Ph] undergoes reaction with 18O2 to produce a
similar level of 18O incorporation (∼65%) in the benzoic acid
product as is found for the reaction involving 2 suggests that
both may proceed via a similar reaction pathway. 18O
incorporation into the carbon-carbon bond cleavage pro-
ducts could occur via reaction of the free triketone with
hydroperoxide to form a five-membered cyclic peroxide
species from which carbon-carbon bond cleavage could
occur. Pochapsky has previously shown that treatment of
2,3,4-pentanetrione with H2O2 results in the formation of CO
and 2 equiv of acetic acid.32 No isotope labeling studies were
reported for this reaction.
control reactions. For example, we are now performing
experiments to examine the reactivity of [(6-Ph2TPA)Ni-
35
(CH3CN)(CH3OH)](ClO4)2
and [(bnpapa)Ni(ClO4)-
(CH3CN)]ClO4 (18) with 1,3-diphenyltriketone and H2O2
to evaluate the efficacy of pathway B chemistry leading to the
observed products. Additionally, we are pursuing kinetic
studies of the reactions of complexes 2 and 14 with O2, as
well as examining the reactivity of [Me4N][PhC(O)C(OH)-
C(O)Ph] with O2 via computational methods to assess its
reactivity relative to that found in the native C(1)-H acir-
eductone substrate processed by the acireductone dioxy-
genases.36
Conclusions
Using the hydrogen-bond donor ligand bnpapa, a mono-
nuclear Ni(II) complex of the formula [(bnpapa)Ni(PhC(O)-
C(OH)C(O)Ph)]ClO4 (14) has been isolated and character-
ized. On the basis of comparison of the spectroscopic features
of this complex to those of air stable analogues, the structure
of 14 is proposed to be generally similar to that previously
reported for [(6-Ph2TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4
(2). Notably, complexes 2 and 14 exhibit differences in
their O2-dependent aliphatic carbon-carbon bond cleavage
reactivity in terms of the product mixture generated and the
level of 18O incorporation in the benzoate/benzoic acid
products. Two possible reaction pathways leading to 18O
incorporation into the benzoate/benzoic acid products are
proposed, with one pathway involving the formation of a
triketone and hydroperoxide anion. Comparison of the
chemical features of several bnpapa- and 6-Ph2TPA-ligated
complexes suggests that differences in the pocket size and
anion binding properties for these two ligand types may be
key factors in producing the observed differences in reaction
products.
The higher level of 18O incorporation in the benzoate/
benzoic acid products of the reaction involving 14 is inter-
esting. On the basis of the results of our current experiments,
it is unclear whether exclusively pathway B chemistry is
occurring in the O2 reactions of 14 and 2, or whether a por-
tion of the labeled product is generated via pathway A type
reactivity. If exclusively pathway B chemistry is operative, an
important distinction between the two supporting chelate
ligand systems is that the bnpapa-ligated Ni(II) center may
coordinate the hydroperoxide anion within the hydrogen
bond donor pocket. The bnpapa chelate ligand has been
previously used to stabilize mononuclear Zn(II) and Cu(II)
hydroperoxide complexes.33,34 To date, similar complexes
have not been reported using the 6-Ph2TPA ligand. Thus,
differences in the anion coordination properties between the
bnpapa and 6-Ph2TPA-supported complexes could contri-
bute to the observed differences in reactivity between 2
and 14.
Acknowledgment. The authors thank the National
Science Foundation (CHE-0848858) and the National
Institutes of Health (1R15GM072509) for financial sup-
port of this research.
Supporting Information Available: X-ray crystallographic
(CIF) files for 16, 17 1/4AHA, 18 CH2Cl2, and 19 2CH2Cl2;
The results of this investigation have enabled the formula-
tion of hypotheses regarding the reaction pathways of 2 and
14 with O2 (Scheme 5) that can now be tested in individual
3
3
3
a drawing showing the level of 2H incorporation in the bnpapa
ligand used for 2H NMR studies; drawings of the ∼20-80 ppm
1
region of the H NMR spectra of 18 and 19. This material is
available free of charge via the Internet at http://pubs.acs.org.
(31) Rubin, M. B.; Gleiter, R. Chem. Rev. 2000, 100, 1121–1164.
(32) Dai, Y.; Pochapsky, T. C.; Abeles, R. H. Biochemistry 2001, 40,
6379–6387.
(33) Wada, A.; Yamaguchi, S.; Jitsukawa, K.; Masuda, H. Angew. Chem.,
Int. Ed. 2005, 44, 5698–5701.
(35) Makowska-Grzyska, M. M.; Szajna, E.; Shipley, C.; Arif, A. M.;
Mitchell, M. H.; Halfen, J. A.; Berreau, L. M. Inorg. Chem. 2003, 42, 7472–
7488.
(34) Fujii, T.; Yamaguchi, S.; Hirota, S.; Masuda, H. Dalton Trans. 2008,
164–170.
(36) Borowski, T.; Bassan, A.; Siegbahn, P. E. M. J. Mol. Struct.
THEOCHEM 2006, 772, 89–92.