A computational investigation into the catalytic activity of a diselenolene sulfite oxidase biomimetic complex

TL;DR: In this paper, the authors compared the molybdenum-diselenolene sulfite oxidase biomimetic complex with the analogous dithiolene-molybdopterin complex.

Abstract: Molybdenum is the only 4d metal found in almost all life. One such molybdenum-containing enzyme is sulfite oxidase, which also contains the dithiolene-molybdopterin ligand. Sulfite oxidase is essential in the degradation of sulfur-containing compounds such as cysteine and methionine. Past work has shown parallels in the chemistry of dithiolene–metal and diselenolene–metal complexes. Thus, in this present work, the oxygen atom transfer mechanism for a diselenolene sulfite oxidase biomimetic complex was investigated using computational tools, the results of which were compared to the analogous dithiolene biomimetic complex. From the results obtained, the molybdenum-diselenolene sulfite oxidase biomimetic complex is able to catalyse the oxygen atom transfer and does so with a marginally lower value of ΔrG‡ than that for the analogous dithiolene complex. In particular, it was found that on average, the diselenolene complex had an activation energy 1.2 kJ mol–1 lower in energy than the analogous dithiolene com...

Summary

Introduction

• Molybdenum (Mo) is the only 4d-metal found in almost all life.
• The alternative mechanism involves the formation of 7-coordinate intermediate whereby the substrate first binds to the Mo center followed by an oxo-transfer to form product.
• Due to the presence of one or more oxo-ligands highly oxidized metal centers are required.
• This enzyme is essential in the degradation of sulfur containing compounds such as cysteine and methionine.
• 18-19 Thus, in this present work the O-atom transfer mechanism is investigated to determine the aqueous Gibbs activation energy and the aqueous Gibbs reaction energy for oxo-transfer by the diselenolene sulfite oxidase biomimetic complex.

Computational Methods

• The Gaussian 09 software suite was used to obtain optimized geometries and aqueous Gibbs reaction energies.
• 26-27 Single point energies were obtained at the IEFPCM-B3LYP/BS2 level of theory.
• The addition of the D3 and D3BJ corrections were used to investigate the effect of dispersion interactions on the oxo-transfer reaction energies.
• The D3 corrections represent the D3 version of Grimme’s dispersion corrections.
• 41-45 The contribution of the transferring O-atom and Mo atom to the LUMO of the diselenolene complex and the contributions of the sulfur atoms to the HOMO of the sulfite was calculated at the BP86/TZ2P level of theory using the ADF program suite.

SO3

• 2– was modeled as protonated given the generally accepted pKa value of 7.21.
• Regarding dithiolene complexes it has been suggested that the dithiolene ligand trans to Oe promotes the transfer of this oxygen rather than Oa. 3, 47 Thus, given the contribution of Oe to the LUMO and the likely trans effect of the diselenolene ligand only the transfer of Oe-atom was examined.
• Like the case for the oxidized complex the water is found to act as a H-bonding donor, however, in the TS the water now forms a medium strength hydrogen bond to one of the oxygens of HSO3 – with a H-bond distance of 1.961 Å .
• The reason why the M06 functional predicts the oxo-transfer to be considerable less endergonic whereas all other methods predict a considerable endergonic reaction is not exactly known.

Conclusions

• From the results obtained in the present study the diselenolene SO biomimetic complex is able to catalyse the O-atom transfer with lower values of ∆rG ‡ in comparison to the analogous dithiolene complex.
• In particular, for the complex it was found that the diselenolene complex has an activation energy that is on average 1.2 kJ mol–1 lower.
• The thermodynamics suggest the oxidation of sulfite is less favourable for the diselenolene complex than that seen for the dithiolene complex where the aqueous Gibbs reaction energy for the dithiolene complex.
• Such results provide incentive for the synthesis of diselenolene complexes.
• Thus, it seems that for oxotransfer reactions catalysed by biomimetic mononuclear Mo-containing complexes the proper treatment of dispersion interaction is necessary.

Figures

Figure 1. The biomimetic diselenolene complex used to model the oxo-transfer reaction of SO in the oxidation of sulfite. The non-attacking Oa was modeled as both protonated and deprotonated, however, for purposes of clarity the proton was not included in the figure.

Figure 2. (a) The LUMO of the L'LMoO(OH2) complex (the water has been ignored for purposes of clarity) and (b) the HOMO of HSO3 –. Obtained at the IEFPPCMB3LYP/BS2//BP86/BS1 and generated using GaussView 5.

Figure 5. The structure of the reduced diselenolene complex product complex, L'LMoOH(OH2), with key bond lengths provided in angstroms. Bond lengths for the dithiolene complex are provided in the parentheses.

Figure 6. a) The structure of the oxidized diselenolene complex, L'LMoO2, in the absence of the water molecule. b) The structure of the TS for the oxo-transfer process in the absence of the water molecule. Key bond lengths provided in angstroms (Å). Bond lengths for the dithiolene complex are provided in the parentheses.

Table 1. Relative aqueous Gibbs energies (in kJ mol–1) for the diselenolene complex obtained at the IEFPCM-DFTi/BS2//BP86/BS1 level of theory. Relative energies obtained for dithiolene complex at the DFTi/BS2//BP86/BS1 level of theory are included in parentheses. Energies are relative to the aqueous Gibbs energies of the isolated reactants (i.e., L LMoO and HSO ).

Figure 4. The structure of the TS for the oxo-transfer process with key bond lengths provided in angstroms. Bond lengths for the dithiolene complex are provided in the parentheses.

Figure 3. The structure of the oxidized diselenolene complex, L'LMoO2, with key bond lengths provided in angstroms. Bond lengths for the dithiolene complex are provided in the parentheses.

Full text

Draft
A Computational Investigation Into The Catalytic Activity Of
A Diselenolene Sulfite Oxidase Biomimetic Complex
Journal:
Canadian Journal of Chemistry
Manuscript ID
cjc-2016-0244.R1
Manuscript Type:
Article
Date Submitted by the Author:
21-Jul-2016
Complete List of Authors:
Bushnell, Eric; Brandon University, Chemistry
Keyword:
diselenolene, density functional theory, computational, dithiolene, sulfite
oxidase biomimetic complex
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Canadian Journal of Chemistry

Draft
1
A Computational Investigation Into The Catalytic Activity Of A Diselenolene
Sulfite Oxidase Biomimetic Complex
Eric A. C. Bushnell*
Department of Chemistry, Brandon University, 270-18th Street, Brandon, Manitoba R7A 6A9,
Canada.
Author to whom correspondence should be addressed:
Email: bushnelle@brandonu.ca
Phone: 204 571 7899
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2
Abstract
Molybdenum is the only 4d-metal found in almost all life. One such molybdenum-containing
enzyme is sulfite oxidase which also contains the dithiolene-molybdopterin ligand. Sulfite
oxidase is essential in the degradation of sulfur containing compounds such as cysteine and
methionine. Past work has shown parallels in the chemistry of dithiolene- and diselenolene-metal
complexes. Thus, in this present work the O-atom transfer mechanism for a diselenolene sulfite
oxidase biomimetic complex was investigated using computational tools. The results of which
were compared to the analogous dithiolene biomimetic complex.
From the results obtained the molybdenum-diselenolene sulfite oxidase biomimetic complex is
able to catalyse the O-atom transfer and does so with a marginally lower value of ∆
r
G
‡
than that
for the analogous dithiolene complex. In particular, it was found that on average the diselenolene
complex had an activation energy 1.2 kJ mol
–1
lower in energy than the analogous dithiolene
complex. However, the calculated value of ∆
r
G suggests that the oxidation of sulfite is more
favourable for the dithiolene complex where the average difference in reaction aqueous Gibbs
reaction energy was -9.4 kJ mol
–1
relative to the diselenolene complex.
It is noted that the use of D3 and D3BJ corrections in combination with the B3LYP functional
the barrier for O-atom transfer is lowered by more than 30.0 kJ mol
–1
for both the diselenolene
and dithiolene complexes. Such results suggest that to study such oxo-transfer reactions the
proper treatment of dispersion interaction is necessary.
Keywords: Diselenolene, Density Functional Theory, Computational, Dithiolene, Sulfite
Oxidase Biomimetic Complex
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3
Introduction
Molybdenum (Mo) is the only 4d-metal found in almost all life. In biological systems Mo
most often exists in the active site of an enzyme ligated by the molybdopterin (MPT) ligand;
notably, such enzymes are critical in carbon, nitrogen and sulfur metabolism.
1-4
The mononuclear
Mo-containing enzymes are divided into three main families; Dimethyl sulfide reductase
(DMSOr), xanthine oxidase and sulfite oxidase (SO) which are defined on the sequence and
structure of the oxidized active sites of the enzyme.
4
In general the mononuclear Mo-containing enzymes catalyse oxo-transfer reactions to or from
substrates. It is noted that an oxo-transfer reaction is defined such that: (i) an O-atom is
transferred and not O
2–
, (ii) the change in oxidation state of the metal is due solely to transfer of
the O-atom and (iii) the transferred O-atom is oxidic and is directly bound in a terminal or
bridging mode to the metal.
5
Previous DFT investigations have studied the oxo-transfer
mechanism for DMSOr biomimetic complexes.
6-7
One such study looked at two possible
mechanisms for the oxo-transfer between various mononuclear Mo complexes and various oxo-
atom acceptors/donors. Of the two possible pathways the preferred mechanism involves the lone
pair of electrons of the substrate attacking an oxo-ligand on the Mo via a 6-coordinate transition
state (TS). The alternative mechanism involves the formation of 7-coordinate intermediate
whereby the substrate first binds to the Mo center followed by an oxo-transfer to form product.
Importantly, the direct oxo-transfer (i.e., 6-coordinate TS) mechanism has a considerably lower
rate-determining barrier and is therefore the kinetically preferred pathway.
6
In another study the
oxo-transfer mechanisms between a biomimetic catalyst of DMSOr and several O-atom accepting
substrates were investigated.
7
In all cases a direct O-atom transfer occurs (i.e., 6-coordicate TS).
7
It is noted that in both of the above-mentioned studies the rate-limiting step is the O-atom transfer
step.
7-8
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4
Due to the presence of one or more oxo-ligands highly oxidized metal centers are required. In
particular, the chosen metal cannot be in an oxidation state less than +4, with no more than 4 d-
electrons.
5
However, even with the highly oxidized metal center additional means are required to
stabilize this metal-oxo group. Such stabilization occurs through the folding of the MPT ligand.
9-
10
Importantly, the MPT ligand contains a dithiolene functional group which ligates the metal
center has been suggested to help tune different possible charges at the metal center.
11
In
particular, it is the ability of the dithiolene ligand(s) to fold that provides a mechanism for the
electronic buffering of the high positive charge on the metal center when it cycles between +4 to
+6 oxidation states.
4, 11-14
As mentioned above one enzyme that contains a MPT ligand is SO. This enzyme is essential
in the degradation of sulfur containing compounds such as cysteine and methionine.
13
Deficiencies in the enzyme activity often lead to premature death.
15-17
In particular it contains a
single MPT ligand that ligates the Mo center along with two oxide-oxygen (O
2–
) atoms and active
site cysteine residue.
17
It is noted that recent work has shown the parallels in the chemistry of
dithiolene- and diselenolene-metal complexes.
18-19
Thus, in this present work the O-atom transfer
mechanism is investigated to determine the aqueous Gibbs activation energy and the aqueous
Gibbs reaction energy for oxo-transfer by the diselenolene sulfite oxidase biomimetic complex.
In addition, the O-atom transfer mechanism is investigated for dithiolene sulfite oxidase
biomimetic complex to determine the effect of substituting the S with Se on the aqueous Gibbs
activation energies as well as the thermodynamics of the reaction.
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Frequently asked questions

Q1. What have the authors contributed in "A computational investigation into the catalytic activity of a diselenolene sulfite oxidase biomimetic complex" ?

In this paper, the authors investigated the aqueous Gibbs reaction energy for oxo-transfer reactions with biomimetic complexes.