Activation of Water at the Active-Site Cavity of Zinc Phthalocyanine with Tris(pentafluorophenyl)borane

Article abstract of DOI:10.1002/ejic.201901273

Activation of water bound with Zn²⁺ has attracted much attention as an artificial model of natural enzymes. Despite many attempts, water activation accompanied with a change in the coordination geometry of Zn²⁺ in complexes remains a challenge. In this study, we discover a new structure that is composed of partially protonated zinc phthalocyanine (ZnPc), hydroxide ion, and tris(pentafluorophenyl)borane (TPFB). The coordination of TPFB with water bounded with ZnPc results in the dissociation of water, and the dissociated proton from water moves to one nitrogen atom of the phthalocyanine ring through the intramolecular proton transfer. On the basis of this reaction, the coordination geometry transforms from a five-coordinated to a distorted tetrahedral species. The Zn²⁺-bound hydroxide nucleophile in the ZnPc-TPFB complex attacks amide of ε-caprolactam to produce hydrolyzed 6-aminohexanoic acid in toluene.

Full text of DOI:10.1002/ejic.201901273

A Journal of
Accepted Article
Title: Activation of Water at Active-site Cavity of Zinc Phthalocyanine
with Tris(pentafluorophenyl)borane
Authors: Takuro Ikeuchi, Ryota Kudo, Tatsuya Yoshii, Nagao
Kobayashi, Yu Kitazawa, and Mutsumi Kimura
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To be cited as: Eur. J. Inorg. Chem. 10.1002/ejic.201901273
Link to VoR: http://dx.doi.org/10.1002/ejic.201901273

10.1002/ejic.201901273
European Journal of Inorganic Chemistry
Activation of Water at Active-site Cavity of Zinc Phthalocyanine with
Tris(pentafluorophenyl)borane
Takuro Ikeuchi, Ryota Kudo, Tatsuya Yoshii, Nagao Kobayashi, Yu Kitazawa, and
Mutsumi Kimura*
[*] Prof. M. Kimura & Prof. Y. Kitazawa
Research Initiative for Supra-Materials (RISM), Interdisciplinary Cluster for Cutting
Edge Research (ICCER), Shinshu University
Prof. M. Kimura, Prof. N. Kobayashi, T. Ikeuchi, R. Kudo, T. Yoshii
Department of Chemistry and Materials, Faculty of Textile Science and Technology,
Shinshu University, Ueda 386-8567, Japan
FAX: (+81)268-21-5499
E-mail: mkimura@shinshu-u.ac.jp
Homepage URL: http://funmater.com
[**] This work has been partially supported by Grants-in-Aid for Scientific Research (A)
(No. 15H02172) from the Japan Society for the Promotion of Science (JSPS) of Japan.
We thank Dr. T. Matsumoto (Rigaku Corporation) for the single crystal X-ray structural
analyses.
Keywords: Phthalocyanines, Zn ion, Lewis Acid, Acid-base reaction, Single crystal X-
ray structural analysis
1
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10.1002/ejic.201901273
European Journal of Inorganic Chemistry
Graphical Abstract
Key Topics: Water activation
TOC Text: Coordination of tris(pentafluorophenyl)borane with water bounded with zinc
phthalocyanine results in the dissociation of water, and the dissociated proton from water
moves to one nitrogen atom of the phthalocyanine ring through the intramolecular proton
transfer.
Abstract: Activation of water bound with Zn2+ has attracted much attention as an
artificial model of natural enzymes. Despite many attempts, water activation
accompanied with a change in the coordination geometry of Zn2+ in complexes remains
a challenge. In this study, we discover a new structure that is composed of partially
protonated
zinc
phthalocyanine
(ZnPc),
hydroxide
ion,
and
tris(pentafluorophenyl)borane (TPFB). The coordination of TPFB with water bounded
with ZnPc results in the dissociation of water, and the dissociated proton from water
moves to one nitrogen atom of the phthalocyanine ring through the intramolecular proton
transfer. On the basis of this reaction, the coordination geometry transforms from a five-
coordinated to a distorted tetrahedral species. The Zn2+-bound hydroxide nucleophile in
the ZnPc-TPFB complex attacks amide of e-caprolactam to produce hydrolyzed 6-
aminohexanoic acid in toluene.
Zinc ion (Zn2+) is an essential element for enzymatic activities such as carbonic
anhydrase, carboxypeptidase, alkaline phosphatase, b-lactamase, and alcohol
2
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10.1002/ejic.201901273
European Journal of Inorganic Chemistry
dehydrogenase.[1,2] Since Zn2+ contains a filled d orbital, the Zn2+ ion in biological
systems does not participate in redox reactions and works as a Lewis acid to accept an
electron pair of donor groups of amino acids in proteins and exogenous water.
Furthermore, the ligand-field stabilization energy for the Zn2+ ion is zero in all metal
coordination geometries. The equally accessible coordination geometries of Zn2+ can alter
reactivity to catalyze chemical transformations accompanied by changes in the
geometries. The lack of redox activity, high electron affinity, and flexibility of
coordination geometry give Zn2+ an important role in catalyzing specific acid-base
reactions in biological media. In the active site of carbonic anhydrase, the Zn2+ ion is
coordinated by three imidazole units in peptide and one exchangeable water molecule in
a tetrahedral arrangement.[1] The coordination of Zn2+ with neutral imidazole units
decreases the pKa value of the bounded water by about three units as compared with free
water, thus creating an optically positioned OH- nucleophile that makes attacking the
carbonyl carbon atom of substrates possible. Artificial models of natural zinc
metalloenzymes have been designed to reproduce the molecular recognition and acid-
base properties of natural enzymes.[3] Although the model compounds have exhibited
significantly lower catalytic activities than natural enzymes, these models could elucidate
the intrinsic chemical roles of Zn2+. In this study, we found a change in the coordination
geometries of zinc phthalocyanine (ZnPc) complexes caused by the activation of water
molecules bounded to the central Zn2+ of ZnPc.
ZnPcs have been widely studied as photosensitizers for the photochemical production
of 1Δg O2 from O2[4-6] as well as for the dye-sensitized solar cells[7,8]; however, there have
been no reports on the reactivity of water molecules bounded to the central Zn2+ in ZnPcs
so far. The axial coordination of donor solvents such as acetone and water was confirmed
by the single-crystal X-ray structural characterization of two ZnPcs having bulky
peripheral substituents.[9,10] Bench et al. reported the stable ligation of two acetone
3
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10.1002/ejic.201901273
European Journal of Inorganic Chemistry
molecules with Zn2+ in ZnPc bearing bulky perfluoro(isopropyl) units at the peripheral
positions of the phthalocyanine ring.[9] McKeown et al. succeeded in preparing crystalline
nanoporous materials composed of steric-crowded zinc 2,3,9,10,16,17,23,24-octa(2,6-
diisopropylphenoxy)phthalocyanine 1 with the axial water molecules.[10] The
introduction of bulky substituents around these ZnPcs could prevent the formation of
densely packed cofacial aggregates among ZnPcs and create nanoscopic cavities above
and below the phthalocyanine plane. The O atom of solvent molecules was coordinated
with Zn2+ within the cavities of ZnPcs.
Figure 1. a) Absorption and fluorescence (inset) spectral changes of
1 ([1] = 5.0 µM) by titration with TPFB ([TPFB] = 0-9.0 µM) in
toluene at room temperature. b) MCD spectra of the mixed toluene
solution of 1 ([1] = 5.0 µM) with TPFB ([TPFB] = 7.5 µM).
First, we checked the reactivity of water bounded to 1 with the addition of
tris(pentafluorophenyl)borane (TPFB). TPFB has been used as a strong Lewis acidic
cocatalyst in various reactions.[11-13] Here, TPFB was chosen as the additional receptor
for electron pairing with O atom in the coordinated water. Figure 1a shows the UV-Vis
absorption and fluorescence spectral changes of 1 in toluene due to the addition of TPFB.
The gradual addition of TPFB to the 1 solution generated an isosbestic spectral change
(Figure 1a), and caused a decrease in the Q band at 680 nm together with a rise of a new
4
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10.1002/ejic.201901273
European Journal of Inorganic Chemistry
absorption band at 735 nm. The fluorescence at 688 nm was quenched by the addition of
TPFB as shown in the inset of Figure 1a. In contrast, a metal free Pc and cobalt (II)
complex having the same peripheral units showed no spectral changes in the same
concentration range of TPFB (Figure S1). TPFB can also interact with nitrogen (N) atoms
through the formation of a strong B-N bond[14,15], however, the eight N atoms in the Pc
ring do not form a bond with TPFB. These spectral changes suggest the interaction of
water bounded to the ZnPc core in 1 with TPFB. While single Faraday A-term signals of
magnetic circular dichroism (MCD) for 1 were observed at 675 and 685 nm in
correspondence with the Q band position (Figure S2)[16], these signals disappeared and a
new trough was observed at 732 nm by the addition of TPFB (Figure 1b). Since the peak
position at the trough in the MCD spectrum almost agrees with that of the new absorption
peak, the observed MCD signal of 1 with TPFB is assigned to be a Faraday B term. This
indicates a break in the degeneracy of the LUMO and LUMO+1 energy levels.
5
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10.1002/ejic.201901273
European Journal of Inorganic Chemistry
Figure 2. a) Needle crystal of 1-TPFB complex formed by slow
diffusion of n-hexane into a CHCl3 solution. b) Molecular structures
of 1-TPFB complex with thermal ellipsoid set at 50% probability level.
c) Bond lengths (Å) for 1 and 1-TPFB complex. d) Derivations from
planarity made of 4N or 3N-plain for C and N atoms of 1 and 1-TPFB
complex. ●, ■, and ▴ indicate C, N, and NH, respectively.
To obtain the direct structural information on the complex of 1 with TPFB, we
conducted a single-crystal X-ray structural analysis. McKeown et al. succeeded in
obtaining large cubic crystals of 1 through a slow crystallization with the diffusion of
acetone into a CHCl3 solution of 1.[10] However, the UV-Vis absorption spectrum of 1
with TPFB returned to that of only 1 during the diffusion of acetone, suggesting the
dissociation of complex by acetone. We changed poor solvent from acetone to n-hexane
for the crystal growth of 1 with TPFB. Large crystals with a cubic morphology were
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10.1002/ejic.201901273
European Journal of Inorganic Chemistry
obtained by the crystallization from a CHCl3 solution of 1 by diffusing n-hexane, and the
molecular packing arrangement of 1 in the single crystal [Pn3n space group with 12
molecules of 1 in the unit cell (a = 3.76 nm)] agreed with the reported structure.[10] The
presence of an axial O atom coordinated with the central Zn in the cone-shaped
phthalocyanine core of 1 was also confirmed (Figure S3). The crystal morphology was
changed from a cube to a needle by the addition of TPFB, implying the formation of a
different molecular packing arrangement (Figure 2a). The crystal structure is monoclinic
and belongs to the P21/n space group with four molecules in the unit cell (a = 2.44 nm, b
= 1.64 nm, c = 3.84 nm, b = 96.5°) (Figure S4).
The X-ray structure of the 1-TPFB complex reveals the attachment of the B atom in
TPFB to the O atom coordinated with the Zn of 1, indicating the formation of a Zn-O-B
bond (Figure 2b)[17]. Interestingly, the dissociated proton from water moves to one N atom
of the inside four N atoms of the phthalocyanine ring and the OH- nucleophile is produced
on the basis of this intramolecular proton transfer. Figure 2c shows the distances of Zn-N
bonds in the 1-TPFB complex. Whereas the distances of the Zn-N bonds in 1 are
completely the same (2.030 Å), the four Zn-N distances in the 1-TPFB complex are
different and the position of Zn2+ atom in the Pc ring approaches to the N atom at the
upper left. Moreover, the change in Zn-N bond lengths due to TPFB leads to the skeletal
deformation of the Pc ring as shown in Figure 2d.[18] 1H NMR spectral analysis of the 1-
TPFB complex in toluene-d8 was carried out at room temperature to obtain the structural
information (Figure S5). All proton resonances in the aromatic region and -CH in
isopropyl units shifted upfield compared with 1, revealing the shielding effect of TPFB
on the Pc ring. The appearance of a broad signal around -1.2 ppm supported the
protonation of an internal N atom in the Pc ring as observed in the single-crystal X-ray
structural analysis. The proton signal corresponding to -CH3 in the peripheral isopropyl
units was split into two peaks at 1.2 and 1.4 ppm for the 1-TPFB complex. One
pentafluorobenzene unit in the TPFB for the crystal structure of the 1-TPFB complex was
located near several peripheral isopropyl units lying out of plain of the Pc ring. The
hydrogen bonding between the fluoride of TPFB and protons of the isopropyl units may
result in the creation of two different proton resonances. Thus, the metal coordination
geometry of 1 transforms from a five-coordinated specie to a distorted tetrahedral specie
with the Zn2+ ion coordinating with three N atoms in the Pc ring and one O atom by
bonding of TPFB with an axial water molecule. The observed geometry of the 1-TPFB
7
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10.1002/ejic.201901273
European Journal of Inorganic Chemistry
complex resembles the binding geometry in the active center of natural zinc
metalloenzymes. As far as we know, this is the first report on the dynamic transformation
of metal coordination geometries in ZnPcs.
Figure 3. a) Calculated UV-Vis absorption spectra of 1 (dashed line)
and 1-TPFB complex (solid line). b) Calculated energy diagrams and
selected molecular orbitals of 1 (left) and 1-TPFB complex (right).
Table 1 Calculated transition energies, oscillator strengths f,
and configurations of 1-TPFB complex.
Configurations (Main percentage
Energy / eV (nm)
f
contribution)
1.84 (672)
1.89 (654)
3.35 (370)
3.39 (366)
3.42 (363)
0.38 H→L (94%)
0.36 H→L+1(91%)
0.40 H-3→L (39%), H-4→L (35%)
0.35 H-4→L+1 (38%), H-1→L (22%)
0.38 H-9→L (22%), H-4→L+1 (16%)
Density functional theory (DFT) calculations at the CAM-B3LYP/6-31G* level
(Gaussian 16[19]) were carried out for the 1 and 1-TPFB complex using the results of the
single-crystal X-ray diffraction analysis to enhance our understanding of the
spectroscopic data. The trends in the absorption spectral differences between the 1 and 1-
TPFB complex calculated by time-dependence DFT were in fair agreement with the
trends in the absorption spectral change of the experiment (Figure 3a). The calculated Q
bands of 1 were red-shifted and splitted into two peaks due to bonding with the TPFB. In
Table 1, the configurations for each calculated peak are summarized so as to clarify the
origin of the spectral features. The split Q bands in the 1-TPFB complex can be assigned
8
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10.1002/ejic.201901273
European Journal of Inorganic Chemistry
to the HOMO→LUMO and HOMO→LUMO+1 transitions of the macrocycles. The
Faraday B term observed in the MCD spectrum of the 1-TPFB complex also supports the
splitting of the degenerated LUMO and LUMO+1 energy levels of 1 by bonding with
TPFB.[16] The absorption band at 370 nm (HOMO-3→LUMO HOMO-4→LUMO) is
assignable to the Soret band. Figure 3b shows a calculated energy diagram of the 1 and
1-TPFB complex and the frontier orbitals of HOMO-1 (HOMO-3 and HOMO-4 for 1-
TPFB complex), HOMO, LUMO, and LUMO+1. Both of the calculated energy levels of
HOMO and LUMO for the 1-TPFB complex were lower than those for 1, and the
calculated HOMO-LUMO band gap of the 1-TPFB complex was narrower than that of 1.
Therefore, it is inferred that the coordination of TPFB with the O atom on ZnPc caused
both the HOMO and LUMO energy levels to stabilize, which lead to a narrowing of the
HOMO-LUMO band gap as well as the degeneracy breaking of the LUMO and LUMO+1
energy levels. Whereas the HOMO frontier orbitals of 1 are located homogeneously over
the Pc ring, the HOMO and LUMO+1 orbitals in the 1-TPFB complex delocalize at the
side of the three coordinated N atoms in the distorted tetrahedral geometry.
9
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10.1002/ejic.201901273
European Journal of Inorganic Chemistry
Figure 4. a) UV-Vis absorption spectral change of 1-TPFB complex
by the addition of e-caprolactam. [1] = = 5.0 µM; [TPFB] = = 5.0 µM,
[e-caprolactam] = 0, 5.0, and 20.0 µM. b) Reaction scheme for
hydrolysis of e-caprolactam by 1-TPFB complex.
We investigated the reactivity of Zn2+-bound OH- nucleophile generated by the
activation of water molecule. Figure 4a shows the absorption spectral change of the 1-
TPFB complex in toluene with increasing the concentrations of e-caprolactam at room
temperature. When an e-caprolactam solution was admixed with the toluene solution of
the 1-TPFB complex[20], a sharp Q band peak appeared at 680 nm (Figure 4a), and
hydrolyzed 6-aminohexanoic acid was formed as confirmed by electrospray ionization
time-of-flight mass (ESI-TOF-Ms) spectroscopic analysis. In contrast, the absorption
spectral change and the formation of 6-aminohexanoic acid were observed for the mixed
solution of 1 and e-caprolactam without TPFB. This result suggests that the coordinated
OH- in the 1-TPFB complex can attack to the carbonyl carbon atom of e-caprolactam
while changing the metal coordination geometry of ZnPc (Figure 4b).
In summary, our results provide a new approach to causing the tetrahedral geometry
of ZnPc to be distorted as observed at the active-sites in natural enzymes. According to a
single-crystal X-ray structural analysis of the 1-TPFB complex, the central Zn2+
coordinated with three N atoms in the Pc ring and one OH- within the cavity of 1, and a
proton dissociated from water was transferred to the remaining N atom in the inside of
the Pc ring simultaneously. We found that the hydrolysis of amide in cyclic e-caprolactam
was caused by the amide being attacked by a Zn2+-bound OH- nucleophile in the 1-TPFB
complex in toluene. The flexibility of the coordination geometry in ZnPc can open new
reactions on the basis of the activation of water molecules within the hydrophobic cavity
around ZnPc. Studies are in progress on the design of the hydrophobic cavity in water-
soluble ZnPc to create high local concentrations of OH- as nucleophiles under neutral
aqueous conditions.
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European Journal of Inorganic Chemistry
R. Cammi, J. W. Ochterski, R. L. Martin, K. Morokuma, O. Farkas, J. B. Foresman,
and D. J. Fox, Gaussian, Inc., Wallingford CT, 2016.
[20]e-Caprolactam (61 µg, 0.54 µmol) was added to the mixed toluene solution (1.5 ml)
of 1 (1.0 mg, 0.54µmol) and TPFB (410 µg, 0.80 µmol) at room temperature. After
5 min, the ESI-TOF mass spectrum of the mixed solution diluted with acetonitrile
was obtained to monitor the hydrolysis of e-caprolactam (the peak at m/z = 132.1019
corresponding to 6-aminohexanoic acid).
12
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