# Significant effect of 2nd sphere interactions on the reductive activation of O2 by non-heme iron(II) complexes. Application to the electroassisted oxidation of thioanisole

Amanda Lyn Robinson, Eva Bannerman, Régis Guillot, Christian Herrero, Katell Sénéchal-David, Eric Rivière, Frédéric Banse, Jean-Noël Rebilly

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Amanda Lyn Robinson, Eva Bannerman, Régis Guillot, Christian Herrero, Katell Sénéchal-David, et al.. Significant effect of 2nd sphere interactions on the reductive activation of O2 by non-heme iron(II) complexes. Application to the electroassisted oxidation of thioanisole. European Journal of Inorganic Chemistry, 2024, 27 (11), 10.1002/ejic.202300694. hal-04452607

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# Significant effect of 2nd sphere interactions on the reductive activation of O₂ by non-heme iron(II) complexes. Application to the electroassisted oxidation of thioanisole

Amanda Lyn Robinson, [a] Eva Bannerman, [a] Régis Guillot, [a] Christian Herrero, [a] Eric Rivière, [a] Frédéric Banse,*[a] Jean-Noël Rebilly.* [a]

[a] Dr A. L. Robinson, E. Bannerman, Dr R Guillot, Dr C Herrero, Dr E Rivière, Pr F Banse,* Dr J-N Rebilly.*

Institut de Chimie Moléculaire et des Matériaux d'Orsay

19 avenue des sciences

Université Paris-Saclay, CNRS

91400 Orsay, France

E-mail: jean-noël.rebilly@universite-paris-saclay.fr; frederic.banse@universite-paris-saclay.fr

**Abstract:** New mononuclear non-heme Fe<sup>II</sup> complexes derived from a well-known pentadentate amine/pyridine ligand were synthesized. The new ligand bears an additional OH group on one pyridyl aimed at developing second sphere hydrogen bonds. Two binding modes of the ligand were observed that can be selectively obtained through the choice of the counterion: the OH group develops an intramolecular H-bond with the 6<sup>th</sup> exogenous ligand in the classical mode, or an intermolecular one with the unbound triflate counterion in the alternative mode. The complexes were studied by cyclic voltammetry in the reductive activation of O<sub>2</sub>. The addition of an H-bond improves the O<sub>2</sub> activation potential with a gain of 90 mV in the classical case and 220 mV in the alternative one. The difference is ascribed to the development of stabilizing H-bonds within the Fe<sup>III</sup>-peroxo intermediate with the proximal O atom of peroxo (classical mode) or the distal one (alternative mode). Ultimately, the complex in the alternative mode activates O<sub>2</sub> at -0.5 V vs SCE (500 mV gain compared to free O<sub>2</sub>). We took advantage of this significantly reduced energetic cost to carry out and achieve the electroassisted oxidation of thioanisole by O<sub>2</sub> at -0.5 V vs SCE.

## Introduction

Redox iron metalloenzymes activate O₂ to achieve the selective oxidation of a variety of molecules in very mild conditions. [1-6] For this purpose, several crucial patterns are ubiquitous in both heme and non-heme systems. The first is the so-called reductive O₂ activation process.[4] Due to its triplet spin state, dioxygen cannot react spontaneously with singlet organic substrates. To trigger its reactivity, enzymes formally reduce it with two electrons to generate a species capable of carrying out the 2-electron oxidation of the substrate. The electron input is achieved by redox cofactors, either bound to the metal (for instance α-ketoglutarate in non-heme α-KG-dependent enzymes)[5, 7-8] or distant from it, like NADPH, a source of two electrons which are sequentially transferred to the metal active site thanks to a reductase.[2-3, 5, 9] The control of the sequential electron input is crucial in cytochromes P450 in order to achieve the formation of the reactive species and avoid its overreduction. In the catalytic cycle,[2] (P)Fe<sup>III</sup> is reduced to (P)Fe<sup>II</sup> by the first electron, which can then bind O₂ to form the superoxo species (P)Fe<sup>III</sup>-OO•. The

second electron reduces it to Fe<sup>III</sup>-peroxo (P)Fe<sup>III</sup>-OO•, which is then protonated to form Fe<sup>III</sup>-hydroperoxo (P)Fe<sup>III</sup>-OOH. Another protonation of the distal O atom of hydroperoxo induces the heterolytic O-O bond cleavage to form the active species, compound I, (P*)Fe<sup>V</sup>=O. The key aspect of O₂ activation is thus the injection of an electron in an Fe<sup>II</sup>/O₂ adduct. This strategy was used with model systems by injecting electrons via an electrode.[10-24] Recently, we studied the activation mechanism of O₂ by the complex [(TPEN)Fe<sup>II</sup>](PF₆)₂.[25-26] It was characterized in cyclic voltammetry by the presence of a "prewave", assigned to the reduction of the Fe<sup>II</sup>/O₂ adduct, occurring before the reduction of free O₂ (e.g. at a more positive potential), making the O₂ reduction process less energetic. However, this potential gain remained limited. Exploiting the push strategy of cytochrome P450 (i.e. increasing the donating character of the 1<sup>st</sup> coordination sphere to favor the Fe<sup>II</sup> to O₂ electron transfer and formation of the superoxo species), we achieved the reductive activation of O₂ by the complex [(L<sub>2</sub>)Fe<sup>III</sup>(OTf)], L₂ being a dianionic ligand, at a potential 500 mV higher than with [(TPEN)Fe<sup>II</sup>](PF₆)₂.[27]

Cytochromes P450 also use pull effects in order to favor O₂ activation: 2<sup>nd</sup> sphere cationic, acidic, and hydrogen bonding residues form an hydrogen bonding network between the distal O atom in the (P)Fe<sup>III</sup>-OO• and the bulk.[2] They stabilize the negative charge forming at the distal O atom of the nascent (P)Fe<sup>III</sup>-OO•, and thus favor the reduction of its precursor (P)Fe<sup>III</sup>-OO•.

With this strategy in mind, we herein report a new ligand L<sub>5</sub><sup>2(OH)</sup> derived from the classic pentadentate aminopyridine ligand L<sub>5</sub><sup>2</sup> by appending an OH hydrogen-bond donor on the ortho position of one of the pyridines. Unexpectedly, L<sub>5</sub><sup>2(OH)</sup> shows two types of binding modes with different 2<sup>nd</sup> sphere hydrogen bonding patterns, which can be selectively obtained by a judicious choice of the metal salt. Addition of the 2<sup>nd</sup> sphere group generates a 90- mV gain in the O₂ activation potential when it is structurally oriented to be able to develop a H-bond with the proximal O in the Fe/O₂ adduct and an even larger gain of 250 mV when the H-bond donor is oriented in such a way that it cannot. We propose a putative interaction with the distal O atom (intra- or intermolecularly, to rationalize this observation. This suggests that a controlled pull effect can significantly reduce the energetic cost of the O₂ activation process.
# Results and Discussion

## Ligand synthesis

$L_5^{2(OMe)}$ was synthesized from 6-methoxy-2-pyridinecarboxaldehyde and $N,N'$-bis(2-pyridylmethyl)ethylenediamine following a procedure reported for ligand $L_5^{2}$. [28-30] Demethylation of $L_5^{2(OMe)}$ was achieved using a nucleophile (Cl⁻) in acidic medium (Scheme 1) to yield $L_5^{2(OH)}$ bearing a 2-pyridone group (Supporting Information, Synthetic procedures and Figures S1-S8). [31]

<figure><img src="image_2.png" /><figcaption>Scheme 1. Synthetic scheme of $L_5^{2(OMe)}$ and $L_5^{2(OH)}$.</figcaption></figure>

## Synthesis and characterization of complexes

### $[L_5^{2(OH)}FeCl](PF_6)$ (1) and $[L_5^{2(OH)}Fe(OTf)](OTf)$ (2)

$[L_5^{2(OH)}FeCl](PF_6)$ (1) was synthesized by reaction of $Fe^{II}Cl_2$ with $L_5^{2(OH)}$ in methanol followed by precipitation upon addition of NaPF₆. $[L_5^{2(OH)}Fe(OTf)](OTf)$ (2) was synthesized by reaction of $Fe^{II}(OTf)_2$ with ligand $L_5^{2(OH)}$ (see Supporting Information).

### Solid state characterization

Single crystals of $[L_5^{2(OH)}FeCl](PF_6)$ (1) and $[L_5^{2(OH)}Fe(OTf)](OTf)$ (2) were obtained from the methanol/$Et_2O$ filtrate during synthesis. The XRD structures of $[L_5^{2(OH)}FeCl](PF_6)$ (1) and $[L_5^{2(OH)}Fe(OTf)](OTf)$ (2) are displayed in Figure 1. In both complexes, ligand $L_5^{2(OH)}$ act as a pentadentate ligand wrapping around the pseudo-octahedral iron center and leaving a 6th position available for an exogenous ligand (chloride or triflate). Another common feature is the binding mode of the 2-pyridone group of $L_5^{2(OH)}$. The iron center is bound through the nitrogen, which loses its hydrogen and transfers it to the neighboring oxygen atom. Thus, the 2-pyridone is bound to the metal in its tautomer form, 2-hydroxypyridine. This coordination-induced equilibrium displacement between 2-pyridone and 2-hydroxypyridine was already reported by Szymczak with TPA-types ligands. [32-33]

However, depending on the complex, two binding modes of these pentadentate ligands can be distinguished.

In $[L_5^{2(OH)}FeCl](PF_6)$ the two pyridyl groups sitting in *trans* positions are linked to two different amines of the ethylene diamine bridge (Figure 1 a/) and lie in nearly perpendicular planes. As a result of this arrangement, one of the pyridyl groups sits in the equatorial plane of the complex (with respect to the Fe-Cl axis), while the other two sit in planes that nearly contain the Fe-Cl axis (scheme 2a). This binding mode will be referred to as the “classical mode” as it is, to the best of our knowledge, the only one reported in the CDCC for Fe(II) complexes of pentadentate ligand $L_5^2$ and its derivatives bearing the same coordinating pentadentate amino-pyridine backbone with pyridines unfunctionalized on the *ortho* position. [30, 34-50]

<figure><img src="image_3.png" /><figcaption>Figure 1. Views of the metal cations in the XRD structures of complexes of $[L_5^{2(OH)}Fe^{II}(Cl)](PF_6)$ (1) (a/), $[L_5^{2(OH)}Fe^{II}(OTf)](OTf)$ (2) (b/). Fe is in orange, C in grey, N in blue, O in red, Cl in green, F in lime, S in yellow. Hydrogen atoms are omitted for clarity, except for those involved in hydrogen bonds.</figcaption></figure>

Conversely, in $[L_5^{2(OH)}Fe(OTf)](OTf)$ (2) (Figure 1 b/), the two pyridyls in *trans* positions are connected to the same amine group of the ethylene diamine bridge. These two groups lie in the equatorial plane (with respect to the Fe-X axis, X = OTf) while the third pyridine lies in the plane that nearly contains the Fe-OTf axis (Scheme 2b). This binding mode will be referred to as the “alternative mode”, as, to the best of our knowledge, it is the first time such a wrapping is reported in an $Fe^{II}$ complex of $L_5^2$ ligand derivatives.

The Fe-N bond lengths sit in the range 2.20-2.25 Å for the complex $[L_5^{2(OH)}FeCl](PF_6)$ (1) displaying the classical binding mode, and in the range 2.15-2.25 Å for the complexe $[L_5^{2(OH)}Fe(OTf)](OTf)$ (2) displaying the alternative binding mode. This suggests a high spin state ($S = 2$) in all cases, as bond distances are expected to be close to 2 Å for a low spin state (S
= 0).[34, 51] This result is in line with a (N₅)FeII(X), where X is an anionic, π-donating, exogenous ligand.

Finally, L₅<sup>2(OH)</sup> complexes display specific hydrogen bonds in the crystal, thanks to the OH group of 2-hydroxypyridine, which acts as a H-bond donor. In the structure of [L₅<sup>2(OH)</sup>FeCl](PF₆) (1), 2-hydroxypyridine sits in the axial plane π<sub>ax2</sub> (Figure 1a, Scheme 2a, classical mode) and is preorganized to hydrogen-bond to the chloro ligand occupying the axial site (d<sub>C1...H</sub> = 2.208 Å). This pattern can only occur in complexes displaying the classical mode (Scheme 2a). Such a pattern was already observed with other ligands bearing 2-hydroxypyridine,<sup>[32-33]</sup> 2-(alkylamino)pyridine<sup>[52-54]</sup> or 2-(acylamino)pyridine<sup>[42]</sup> groups.

<figure><img src="image_4.png" /><figcaption>**Scheme 2.** Description of the two binding modes with L₅<sup>2</sup>-type ligands. Classical mode (a/), and alternative mode (b/).</figcaption></figure>

In [L<sub>5</sub><sup>2(OH)</sup>Fe(OTf)](OTf) (2), displaying the alternative mode, 2-hydroxypyridine sits in the equatorial plane π<sub>eq</sub> (Scheme 2b, alternative mode) and cannot generate hydrogen bonding with the bound O atom of triflate. Instead, the OH group projects outward and is hydrogen-bonded to the unbound triflate in the unit cell (d<sub>TFO...H</sub> = 1.642 Å).

Comparison of the structure of [L<sub>5</sub><sup>2(OH)</sup>FeCl](PF<sub>6</sub>) (1) and parent complex deprived of hydroxy group [L<sub>5</sub><sup>2</sup>FeCl](BPh<sub>4</sub>)<sup>[34]</sup> shows a similar coordination sphere. However, the Fe-N bond length between the iron and the bound 2-hydroxypyridine in (1) is increased with respect to [L<sub>5</sub><sup>2</sup>FeCl](BPh<sub>4</sub>) (2.235 Å instead of 2.171 Å) due to the increased bulk, while the Cl-Fe-N angle involving 2-hydroxypyridine in (1) is decreased from 106.79° to 101.40° with respect to [L<sub>5</sub><sup>2</sup>FeCl](BPh<sub>4</sub>), in line with the optimization of hydrogen bonding.

## Solution characterization

In the following electrochemistry discussion, the coordination sphere of the species will be described using (N<sub>5</sub><sup>c</sup>) for the classical pentadentate binding mode and (N<sub>5</sub><sup>a</sup>) for the alternative one, and (N<sub>4</sub>) for the tetradentate binding mode (decoordination of one pyridine).

The cyclovoltammogram (CV) of [L<sub>5</sub><sup>2(OH)</sup>FeCl](PF<sub>6</sub>) (1) in MeCN shows a predominant quasi reversible wave at E<sub>1/2</sub> = 0.7 V (ΔE = 120 mV, Figure S11), assigned to a complex in which L<sub>5</sub><sup>2(OH)</sup> binds in a pentadentate fashion, and completes its coordination sphere with an anionic exogenous ligand, by analogy with parent complexes.[30] On the reverse scan (reduction), three waves are detected suggesting equilibria with the solvent at the Fe<sup>III</sup> state: E<sub>p</sub><sup>c</sup> = 0.92 V ([(N<sub>5</sub><sup>c</sup>)Fe<sup>III</sup>(MeCN)]<sup>3+</sup> species), E<sub>p</sub><sup>c</sup> = 0.64 V ([(N<sub>5</sub><sup>c</sup>)Fe<sup>III</sup>Cl]<sup>2+</sup> species) and E<sub>p</sub><sup>c</sup> = 0.34 V ([(N<sub>4</sub>)Fe<sup>III</sup>Cl]<sup>+</sup> species.[30] At more negative potentials, a reduction wave at E<sub>p</sub><sup>c</sup> = -1.81 V is tentatively ascribed to the reduction of a pyridine bound to Fe<sup>II</sup>, by analogy with the Zn<sup>II</sup> titration of the ligand where a similar wave is observed at E<sub>p</sub><sup>c</sup> = -1.73 V (Figure S9). In the [L<sub>5</sub><sup>2</sup>Fe(MeCN)](PF<sub>6</sub>)<sub>2</sub> complex,[50] a similar reduction wave is observed at -1.70 V (Figure S9c).

The UV-vis absorption spectrum of [L<sub>5</sub><sup>2(OH)</sup>FeCl](PF<sub>6</sub>) (1) in MeCN displays MLCT absorption bands at λ = 372 nm (ε = 1920 M<sup>-1</sup>·cm<sup>-1</sup>) (Figure S12). The low values of the extinction coefficients are in line with a high spin state, confirmed by Evans NMR (84% HS at 300 K in CD<sub>3</sub>CN, Figure S13). A high spin state is consistent with a (N<sub>5</sub>)Fe<sup>II</sup>Cl formulation. Thus, the structure of [L<sub>5</sub><sup>2(OH)</sup>FeCl](PF<sub>6</sub>) (1) is retained in solution.

The CV of crystals of [L<sub>5</sub><sup>2(OH)</sup>Fe(OTf)](OTf) (2) (Figure S15) shows an oxidation wave at E<sub>p</sub><sup>a</sup> = 1.03 V of a poorly reversible couple, ascribed to [(N<sub>5</sub><sup>a</sup>)Fe<sup>II</sup>(MeCN)]<sup>2+</sup>. On the reverse scan, the reduction of the corresponding species is found at E<sub>p</sub><sup>c</sup> = 0.89 V (E<sub>1/2</sub> = 0.96 V, ΔE = 140 mV), along with another wave at E<sub>p</sub><sup>c</sup> = 0.49 V. By analogy with parent complexes, these reduction potentials are ascribed to species [(N<sub>5</sub><sup>a</sup>)Fe<sup>III</sup>(MeCN)]<sup>3+</sup>, and [(N<sub>5</sub><sup>a</sup>)Fe<sup>III</sup>(OH)]<sup>2+</sup> respectively (Table S1). As expected, the labile triflate ligand is substituted by MeCN.

The UV-vis spectrum in MeCN of the crystals of [L<sub>5</sub><sup>2(OH)</sup>Fe(OTf)](OTf) (2) (Figure S17) displays MLCT absorption bands at λ = 362 nm (ε = 1510 M<sup>-1</sup>·cm<sup>-1</sup>). NMR characterization by the Evans method indicates the complex is predominantly HS (76%) in CD<sub>3</sub>CN at 300 K (Figure S18).

At this point, the reason for the appearance of this unusual alternative coordination mode of a L<sub>5</sub><sup>2</sup>-type ligand in [L<sub>5</sub><sup>2(OH)</sup>Fe(OTf)](OTf) (2) was puzzling. A first hypothesis was that the bulkiness of the bound anion might direct the binding mode of the ligand: with the larger triflate (vs chloro), the classical binding mode could be sterically disfavored. However, Que et al. reported the structure of [(BnTPEN)Fe<sup>II</sup>(OTf)](OTf), with a L<sub>5</sub><sup>2</sup>-type ligand bearing a benzyl pendant group instead of methyl and the complex displayed the classical binding mode.[35] It thus appears that this alternative wrapping likely results from the simultaneous presence of the OH group in the ortho position of pyridine and a bound triflate (vide infra). To confirm this hypothesis, we synthesized the complex [L<sub>5</sub><sup>2(OMe)</sup>Fe(OTf)](OTf) (3).

[L<sub>5</sub><sup>2(OMe)</sup>Fe(OTf)](OTf) (3)
[L₅²(OMe)Fe(OTf)](OTf) (3) was synthesized by reaction of Fe''(OTf)₂ with the ligand L₅²(OMe) in MeOH, followed by precipitation by addition of diethyl ether.

## Solid state characterization

Single crystals of [L₅²(OMe)Fe(OTf)](OTf) (3) were obtained by diffusion of diethyl ether in a methanolic solution of the complex. The X-ray structure of [L₅²(OMe)Fe(OTf)](OTf) (3) is displayed in Figure 2. The L₅²(OMe) ligand is bound in the alternative binding mode (Scheme 2), as observed in the structure of [L₅²(OH)Fe''(OTf)](OTf) (2) (Figure 1). The OMe group of the methoxypyridine lies in the equatorial plane. A bound triflate in [L₅²(OMe)Fe(OTf)](OTf) (3) completes the coordination sphere. The Fe-N bond lengths sit in the range 2.15-2.23 Å in line with a high spin complex.[³⁴, ⁵¹]

<figure><img src="image_5.png" /><figcaption>**Figure 2.** View of the metal cation in the XRD structures of complexes of [L₅²(OMe)Fe(OTf)](OTf) (3). Fe is in orange, C in grey, N in blue, O in red, Cl in green, F in lime, S in yellow. Hydrogen atoms are omitted for clarity, except for those involved in hydrogen bonds.</figcaption></figure>

## Solution characterization

The CV of crystals of [L₅²(OMe)Fe(OTf)](OTf) (Figure S20) shows a quasi-reversible oxidation wave at E₁/₂ = 0.98 V (ΔE = 130 mV), ascribed to the [(N₅³)FeIII/II(MeCN)]³⁺/²⁺ couple. On the reverse scan, a minor reduction wave is observed at Eₚ = 0.52 V. By analogy with parent complexes, this reduction potential is ascribed to the reduction of a [(N₅³)FeIII(X)]²⁺ species, X being an anion (triflate or hydroxide). The structure of [L₅²(OMe)Fe(OTf)]⁺ is not maintained in solution and the triflate ligand is, as expected, exchanged for MeCN. The UV-vis spectrum in MeCN of the crystals of [L₅²(OMe)Fe(OTf)](OTf) (3) (Figure S21) is very similar to the one of [L₅²(OH)Fe(OTf)](OTf) (2) (see above Figure S17) : the complex displays a MLCT absorption band at λ = 364 nm (ε = 1600 M⁻¹·cm⁻¹) in MeCN. NMR characterization by the Evans method indicates the complex is predominantly HS (91%) in CD₃CN at 300 K (Figure S22). [L₅²(OH)Fe(OTf)](OTf) and [L₅²(OMe)Fe(OTf)](OTf) also display very similar NMR spectra (Figure S23) supporting the fact they display the same binding mode.

<figure><img src="image_6.png" /><figcaption>**Scheme 3.** Views of the repulsive electrostatic interactions that would develop in the discarded classical binding mode of L₅²(OMe) and L₅²(OH) in comparison with the absence of such interactions in the favored alternative binding mode.</figcaption></figure>

The structure of [L₅²(OMe)Fe(OTf)](OTf) (3) confirms that the alternative mode observed in [L₅²(OH)Fe''(OTf)](OTf) (2) arises from the simultaneous presence of a bound triflate and a OH/OMe group in ortho position of one pyridine. During synthesis in MeOH, a poorly competitive ligand, it is likely that triflate remains bound to Fe'' prior to the coordination of L₅²(OH) or L₅²(OMe). If L₅²(OH) or L₅²(OMe) were to bind Fe'' in the classical binding mode, the 2-hydroxypyridine or 2-methoxypyridine would be forced to lie in one of the axial planes π<sub>ax1</sub> or π<sub>ax2</sub> (Scheme 2). In the case of L₅²(OMe), the methyl group of the methoxy would project outwards for steric reasons, thus forcing the lone pairs of oxygen to be oriented towards the binding site of triflate. A repulsive electrostatic interaction would then develop between them and the lone pairs of the binding O atom of triflate (Scheme 3). In the case of L₅²(OH), a hydrogen bond between the OH group of 2-hydroxypyridine (H-bond donor) and the bound O atom of triflate would be expected to form by analogy with the structure of [L₅²(OH)FeCl](PF₆) (1). The lone pairs of the O atom of 2-hydroxypyridine would thus be oriented outwards but repulsive electrostatic interactions would develop between them and the lone pairs of the F atoms of triflate, given the orientation imposed to the bound counterion by the hydrogen bond (Scheme 3). Conversely, in the alternative mode, where the functionalized pyridine lies in the equatorial plane (Schemes 2 and 3), the repulsive interactions vanish. With the less bulky chloride in [L₅²(OH)FeCl](PF₆) (1), no repulsive interaction is present and the classical binding mode remains the favored one. It is even further stabilized by hydrogen bonding. Drastic effects of such unfavorable interactions are not unprecedented in coordination chemistry. Izzet *et al* reported the comparative binding properties of Cu'' complexes of tripodal ligands grafted onto a calix[6]arene cavity *via* ether bridges. Depending on the cap, the orientation of the lone pairs of the O atoms of the ether bridges could be controlled and oriented either outwards or towards the binding site
within the cavity. In the former case, the complex was able to bind
a variety of anions whereas in the latter case, anion binding was
completely discarded.[55]

By the choice of the starting iron salt (chloride or triflate), it is thus
possible to selectively obtain complexes in the classical or
alternative binding mode of L₅²(OH). Each mode displays a different
H-bonding pattern with the ligand on the 6th coordination site. Our
aim being to study the impact of such hydrogen bonds on the
performance of O₂ reductive activation, we needed an easily
exchangeable ligand at the 6th site of iron. Triflate fulfills this
requirement and [L₅²(OH)FeI'(OTf)](OTf) (2) is a good candidate to
study the alternative binding mode. However, for the classical
binding mode, [L₅²(OH)FeCl](PF₆) (1) is not, as chloride is a strong
competitor of O₂ for coordination. Attempts to remove chloride
using silver nitrate and isolate the resulting complex were
unsuccessful. We thus tried to isolate a complex starting from the
Fe(H₂O)₆·(BF₄)₂ salt, as the counterions are not coordinating and
the remaining ligand, H₂O, is perfectly suited to fit in the classical
binding mode and to develop a hydrogen bond with the *ortho* OH
group without repulsive interactions.

[(L₅²(OH))Fe(OH)]BPh₄ (4)

[([L₅²(OH)]Fe(OH)]BPh₄ (4) was obtained by the addition of NaBPh₄ to a methanol solution containing equimolar amounts of L₅²(OH) and [Fe(H₂O)₆](BF₄)₂. Single crystal suitable for X-ray diffraction were obtained in the methanol filtrate.

Solid state characterization

<figure><img src="image_7.png" /><figcaption>**Figure 3.** View of the metal cation in the XRD structure of [(L<sub>5</sub><sup>2(OH)</sup>)Fe(OH)]BPh<sub>4</sub> (4). Fe is in orange, C in grey, N in blue, O in red. Hydrogen atoms are omitted for clarity, except for those involved in hydrogen bonds.</figcaption></figure>

Ligand L₅²(OH) acts as pentadentate ligands wrapping around the pseudo-octahedral iron center and leaving a 6th position available for an hydroxo ligand (Figure 3). L₅²(OH) is bound in the classical binding mode, and the first coordination sphere is similar to that of iron in [L₅²(OH)FeCl](PF₆) by replacing Cl⁻ by OH⁻. However, while 2-hydroxypyridine sits in the πₐx₂ plane in [L₅²(OH)FeCl](PF₆), it lies in the πₐx₁ plane in the case of [(L₅²(OH))Fe(OH)]BPh₄ (4). The Fe-N bond lengths are in the range of 2.20-2.25 Å suggesting a high spin state.[34, 51] Fe-OH bond length is 1.955 Å, and the

length of the intramolecular H-bond between the 2-
hydroxypyridine and the O atom of the bound hydroxo ligand is
1.668 Å. Due to the reduced bulkiness of OH⁻ vs Cl⁻, the N<sub>(py-OH)</sub>-
Fe-X angle (X = Cl or OH) is reduced from 101.4° (Cl⁻) to 87.6°
(OH⁻). Interestingly, an intermolecular H-bond also develops in the
unit cell with an external methanol molecule and the bound
hydroxo ligand (d(H<sub>MeOH</sub>-O<sub>OH</sub>) = 1.902 Å).

**Solution characterization**

The CV of [(L₅²(OH))Fe(OH)]BPh₄ (Figure S25) displays a major reversible couple at E₁/₂ = 0.58 V (ΔE = 80 mV) and a much weaker one at E₁/₂ = 0.95 V (ΔE = 80 mV) ascribed to [(N₅ᵃ)FeII(OH)]⁺ and [((N₅ᵃ)FeII(MeCN))²⁺ species respectively. An additional irreversible wave is observed in oxidation at Eₚᵃ = 0.82 V, ascribed to the oxidation of BPh₄⁻. The CV is in line with the structure, with a predominant [(N₅ᵃ)FeII(OH)]⁺ form. The UV-vis spectrum in MeCN (Figure S26) displays an MLCT absorption band at λ = 389 nm (ε = 1600 M⁻¹·cm⁻¹). The spectrum is close to the one of the chloro analogue [(L₅²(OH))FeCl]PF₆ (λ = 372 nm, ε = 1920 M⁻¹·cm⁻¹) in MeCN).

As the BPh₄⁻ counterion is electroactive and might interfere in the O₂ activation process,[56-57] we carried out the synthesis of its BArF analogue.

[(L₅²(O⁻))Fe]₂(BArF)₂ (5)

[([L₅²(O⁻))Fe]₂(BArF)₂ (5) was obtained by reacting equimolar amounts of L₅²(OH) and [Fe(H₂O)₆](BF₄)₂ in the presence of a base (NaOMe, 1 equiv.) in MeOH. Addition of KBArF did not induce precipitation of the compound. The product was isolated by addition of water to the methanol solution, which induced its precipitation. Single crystals suitable for X-ray diffraction were obtained by diffusion of pentane into a CH₂Cl₂ solution of the complex.

**Solid state characterization**

The BArF analogue of [(L₅²(OH))Fe(OH)](BArF) does not crystallize as a mononuclear species, but as a dinuclear one formulated as [(L₅²(O⁻))Fe]₂(BArF)₂ (5) (Figure 4). The ligand is present in the dimer in its deprotonated form L₅²(O⁻). It binds each of the FeII centers in a pentadentate fashion analogous to L₅²(OH) in the classical binding mode. More specifically, the binding mode is the same as L₅²(OH) in [L₅²(OH)FeCl](PF₆), with the functionalized pyridine sitting in the axial plane πₐx₂ (Scheme 2a). The 6th binding site is occupied by the O atom of the L₅²(O⁻) ligand of the other Fe center. The two complexes are thus arranged in a head-to-tail fashion and the O-pyridyl groups are thus bridging the two iron centers.

The Fe-N bond lengths (N<sub>amine</sub> and N<sub>py</sub>) sit in the range 2.19-2.31 Å. The Fe-N<sub>(py-O-)</sub> bonds are slightly shorter (2.13-2.15 Å), in line with a more donating character of the (py-O⁻) group, and the Fe-O bond lengths are in the range 1.97-1.98 Å. This suggests a high spin state locally for each Fe center.[34, 51]
<figure><img src="image_8.png" /><figcaption>**Figure 4.** View of the metal cations in the XRD structures of complexes of [(L<sub>5</sub><sup>2(O-)</sup>)Fe]<sub>2</sub>(BArF)<sub>2</sub> (5). Fe is in orange, C in grey, N in blue, O in red. Hydrogen atoms are omitted for clarity.</figcaption></figure>

Magnetic studies of [(L<sub>5</sub><sup>2(O-)</sup>)Fe]<sub>2</sub>(BArF)<sub>2</sub> (5) (Figure S28) show that the dimer consists of two high spin Fe<sup>II</sup> complexes that are antiferromagnetically coupled with a very weak constant (J = -1 cm<sup>-1</sup>).

## Solution characterization

The CV of [(L<sub>5</sub><sup>2(O-)</sup>)Fe]<sub>2</sub>(BArF)<sub>2</sub> (Figure S29) displays three quasi-reversible oxidation waves in the Fe<sup>III</sup>/<sup>II</sup> region at E<sub>1/2</sub> = 0.35 V (ΔE = 90 mV), E<sub>1/2</sub> = 0.65 V (ΔE = 140 mV), E<sub>1/2</sub> = 0.97 V (ΔE = 170 mV), assigned to a [(N<sub>4</sub>)Fe<sup>III</sup>/<sup>II</sup>(X)<sub>2</sub>]<sup>1+/0</sup>, a [(N<sub>5</sub>)Fe<sup>III</sup>/<sup>II</sup>(X)]<sup>2+/+</sup> and a [(N<sub>5</sub>)Fe<sup>III</sup>/<sup>II</sup>(MeCN)]<sup>3+/2+</sup> species (X = monoanion, likely OH<sup>-</sup>). The potential of the 0.65 V wave could also correspond to the Fe<sup>III</sup>Fe<sup>III</sup>/Fe<sup>III</sup>Fe<sup>II</sup> wave of the dimer itself.

Upon addition of HClO<sub>4</sub> (up to 1 equiv. vs Fe), the first two Fe<sup>III</sup>/<sup>II</sup> waves vanish in favor of the 3<sup>rd</sup> one, in line with acid-base related species (Figure S30, S31). It can be concluded that the dimer is present in various forms in equilibrium in solution (Scheme 4). This equilibrium can be displaced towards a quasi-single species [(L<sub>5</sub><sup>2(OH)</sup>)Fe(MeCN)]<sup>2+</sup> upon addition of 1 equiv. HClO<sub>4</sub> (vs Fe). Comparison with the CV of [(L<sub>5</sub><sup>2(OH)</sup>)Fe(OTf)](OTf) (Figure S31, Table S1) shows that the Fe<sup>III</sup>/<sup>II</sup> couples are similar but not exactly the same, especially on the reverse scan upon [(N<sub>5</sub>)Fe<sup>III</sup>(X)]<sup>2+</sup> reduction. The difference is ascribed to different binding modes of L<sub>5</sub><sup>2(OH)</sup>.

The addition of HClO<sub>4</sub> can also be followed by <sup>1</sup>H NMR (Figure S32). The complexes before and after addition remains mostly paramagnetic (Figure S33). The spectrum of the final complex displays peaks that are similar to those found in [(L<sub>5</sub><sup>2(OH)</sup>)Fe(OTf)](OTf) and [(L<sub>5</sub><sup>2(OMe)</sup>)Fe(OTf)](OTf) (Figure S34) in line with a [(N<sub>5</sub>)Fe(MeCN)]<sup>2+</sup> coordination sphere in all cases. However, above 60 ppm, [(L<sub>5</sub><sup>2(OH)</sup>)Fe(OTf)](OTf) and [(L<sub>5</sub><sup>2(OMe)</sup>)Fe(OTf)](OTf) retain the same resonances, while those of [(L<sub>5</sub><sup>2(O-)</sup>)Fe]<sub>2</sub>(BArF)<sub>2</sub> in the presence of HClO<sub>4</sub> are different, in line with the retention of the classical binding mode upon protonation of the dimer [(L<sub>5</sub><sup>2(O-)</sup>)Fe]<sub>2</sub>(BArF)<sub>2</sub>.

<figure><img src="image_9.png" /><figcaption>**Scheme 4.** Equilibria in solution upon dissolution of dimer [(L<sub>5</sub><sup>2(O-)</sup>)Fe]<sub>2</sub>(BArF)<sub>2</sub> (5) in MeCN, and in situ generation of [(L<sub>5</sub><sup>2(OH)</sup>)Fe]<sup>2+</sup> as a single species upon addition of 1 equiv. aqueous HClO<sub>4</sub> (vs Fe).</figcaption></figure>

## Electrochemical studies of the reductive activation of dioxygen

2<sup>nd</sup> sphere interactions are crucial to control the activation of dioxygen in natural systems. In cytochrome P450, cationic residues and H-bond donors form an uninterrupted hydrogen bond network between the bulk (water medium) and the distal O atom in the Fe/O<sub>2</sub> adduct. This makes the reduction of Fe<sup>III</sup>-OO• to Fe<sup>III</sup>-OO<sup>-</sup> easier, as it stabilizes the nascent negative charge, subsequently protonating the distal O to form Fe<sup>III</sup>-OOH.[2]

As evidenced by the structures reported above, the L<sub>5</sub><sup>2(OH)</sup> ligand in the classical binding mode would be constrained to generate a hydrogen bond with the proximal O atom of a Fe/O<sub>2</sub> adduct, while in the alternative binding mode, it could not. In order to evaluate more quantitatively the impact of this 2<sup>nd</sup> sphere hydrogen bond donor (OH) on the O<sub>2</sub> activation process in both binding modes of L<sub>5</sub><sup>2(OH)</sup>, we studied the reductive activation of O<sub>2</sub> by two of the above mentioned complexes: [L<sub>5</sub><sup>2(OH)</sup>Fe<sup>II</sup>(OTf)](OTf) (2), which yields the [(N<sub>5</sub><sup>2</sup>)Fe<sup>II</sup>(MeCN)]<sup>2+</sup> species in MeCN solution (alternative mode), and the dimeric [(L<sub>5</sub><sup>2(O-)</sup>)Fe]<sub>2</sub>(BArF)<sub>2</sub>, as the addition of 1 equiv. HClO<sub>4</sub> (per Fe) generates *in situ* the [(N<sub>5</sub><sup>c</sup>)Fe<sup>II</sup>(MeCN)]<sup>2+</sup> species (classical mode). CVs of the complexes were recorded under air at [Fe] = 1.62 mM, which is the solubility of O<sub>2</sub> in MeCN in these conditions, and allows us to maintain a Fe:air (1:1) ratio through all the CVs.
<figure><img src="image_10.png" /><figcaption>**Figure 5.** CVs at GC electrode of [(L₅²Fe⁸)(MeCN)](PF₆)₂ (blue trace) and [(L₅²(OMe)Fe(OTf))](OTf) (red trace), ([Fe] = 1.62 mM in MeCN, NBu₄PF₆ 0.1 M, CE = Pt; Ref = SCE, 0.1 V·s⁻¹) under air. Full scale (a/) and zoom on the reduction part (b/).</figcaption></figure>

### Impact of the binding mode of the ligand.

As control experiments, we first recorded the CVs under air of complexes deprived of hydrogen bond donor, [(L₅²)Fe⁸(MeCN)](PF₆)₂, with ligand L₅² bound in the classical binding mode, and [(L₅²(OMe))Fe(OTf)](OTf), with ligand L₅²(OMe) bound in the alternative binding mode. Both display very similar CVs under air (Figure 5) that are very close to that reported for complex [(TPEN)Fe](PF₆)₂. In the [(TPEN)Fe](PF₆)₂ case, the O₂ activation mechanism was studied in detail by a combination of spectroscopy of reaction intermediates and simulation of CVs.[25] The wave observed at -1 V vs SCE corresponds to the reduction of free O₂ to superoxide (Figure 5b). In the presence of an Fe⁰ complex, another wave appears at a slightly higher potential (-0.76 V for [(L₅²)Fe⁸(MeCN)](PF₆)₂, -0.72 V for [(L₅²(OMe)Fe(OTf)](OTf)). It corresponds to the reduction of the Fe⁰/O₂ adduct (to Fe³⁻-OO⁻ in a 1st step) and thus to the potential

of the reductive activation of O₂ at the iron center. The mechanism at work at the prewave has been previously described as the square scheme represented in scheme 5.[25]

<figure><img src="image_11.png" /><figcaption>**Scheme 5.** Square scheme representing the reductive O₂ activation process, involving two pathways, an EC one (electrochemical-chemical) and a CE one (chemical-electrochemical).</figcaption></figure>

Thus, the value of the prewave potential quantifies the efficiency of the complex in this process. This preliminary result shows that (i) both complexes are not very efficient O₂ activators as they display a prewave that remains very close to that of the reduction of free O₂, (ii) the binding mode of L₅²-type ligands does not make a significant difference in the activation potential, and (iii) improvement of this activation potential can be expected from ligand tuning.

### Impact of the hydrogen bond donor in the classical binding mode

To evaluate the impact of the hydrogen bond donor in the classical binding mode, the [(N₅²)Fe⁰(MeCN)]²⁺ species has to be generated in solution by reaction of the dimeric [(L₅²(⁰-))Fe]₂(BArF)₂ with 1 equiv. HClO₄ (per Fe).

Under Ar, [(L₅²(⁰-))Fe]₂(BArF)₂ in MeCN is partially dissociated to residual [(L₅²(OH))Fe(OH)]₂ and [(L₅²(OH))Fe(MeCN)]²⁺ (vide supra, Figure S29, Scheme 4). Under air, the starting [(L₅²(⁰-))Fe]₂(BArF)₂ solution (without acid) only shows one prewave at -0.74 V, with a low intensity, together with an even weaker and broader reduction intensity around -0.54 V (Figure S35). Given the poor intensities of the prewaves observed under air without acid, we can conclude that the dimer and the mononuclear species in equilibrium with it are not good activators. Under Ar, and with 1 equiv. of HClO₄ added (per Fe), the main species is [(L₅²(OH))Fe(MeCN)]²⁺ (Figures S30-S31), but as depicted in Scheme 4, a [(L₅²(OH))Fe(OH)]⁺ species is also present, due to the following equilibrium:

$$ [(L_5^{2(OH)})Fe(MeCN)]^{2+} + H_2O \rightleftharpoons [(L_5^{2(OH)})Fe(OH)]^{+} + H^{+} + MeCN \quad (i) $$
<figure><img src="image_12.png" /><figcaption>**Figure 6.** Compared CVs at GC electrode ([Fe] = 1.62 mM in MeCN, NBu₄PF₆ 0.1 M, CE = Pt; Ref = SCE, 0.1 V·s⁻¹) under air of [L₅²(OH)Fe(MeCN)](PF₆)₂ and of a solution of [(L₅²(O-))Fe]₂(BArF)₂ and HClO₄ (1 equiv. per Fe).</figcaption></figure>

Under air, the addition of acid slightly shifts the first prewave from -0.74 V to -0.81 V and induces the appearance of a 2nd one at -0.65 V. Both prewaves grow in intensity during the HClO₄ titration (Figure 6 and S35). The two species present in solution, [(L₅²(OH))Fe(MeCN)]²⁺ and [(L₅²(OH))Fe(OH)]⁺, can thus be considered as responsible for the two observed prewaves.

When an anion is bound to Fe, as in [L₅²(OH)FeCl](PF₆), a prewave is observed at -0.74 V (Figure S36). By analogy, the -0.81 V wave can thus be ascribed to the O₂ activation by a complex with a bound anion, i.e. [(L₅²(OH))Fe(OH)]⁺ species, and consequently, the new wave at -0.65 V is likely due to the O₂ activation by [(L₅²(OH))Fe(MeCN)]²⁺ in the classical binding mode.

The intensity increases of the overall CV in reduction (Figure S35) is ascribed to the presence of protons in the reaction medium, as a result of equilibrium (i): protonation can indeed favor extra electron input at the prewaves.

This is confirmed when pentafluorophenol is used as a source of protons (pKa = 20.11 in MeCN)[⁵⁸] instead of HClO₄ (pKa = 1.57 in MeCN).[⁵⁹] Under Ar, its addition to [(L₅²(O-))Fe]₂(BArF)₂ protonates the residual [(L₅²(OH))Fe(OH)₂] but does not yield a single [(L₅²(OH))Fe(MeCN)]²⁺ species, but a major [(L₅²(OH))Fe(X)]⁺ one (X = anion). (Figure S37). Under air, only a prewave at -0.78 V is observed, assigned to the activation of O₂ by [(L₅²(OH))Fe(X)]⁺ with its intensity increasing with the amount of pentafluorophenol used (Figure S38). However, no extra prewave at more positive potential is observed, even in the presence of extra protons in the reaction medium.

This also confirms that the prewave at -0.65 V is due to the O₂ activation by [(L₅²(OH))Fe(MeCN)]²⁺ in the classical binding mode. Comparison of the prewaves observed with [(L₅²(OH))Fe(MeCN)]²⁺ (-0.65 V) and [(L₅²)Fe(MeCN)]²⁺ (-0.76 V) shows that the addition of the OH hydrogen-bond donor in the ortho position of one

pyridine in the classical binding mode is responsible for a 90-mV shift of the prewave to more positive potentials.

## Impact of the hydrogen bond donor in the alternative binding mode

When a hydrogen bond donor is added in the ortho position of one of the pyridines in the alternative binding mode ([L₅²(OH)Fe(OTf)](OTf)), a single prewave is observed at -0.50 V (Figure 7). When compared to its counterpart deprived of hydrogen bond donor [L₅²(OMe)Fe(OTf)](OTf), this represents a gain of 220 mV for the prewave potential and thus the O₂ activation process.

<figure><img src="image_13.png" /><figcaption>**Figure 7.** Compared CVs at GC electrode ([Fe] = 1.62 mM in MeCN, NBu₄PF₆ 0.1 M, CE = Pt; Ref = SCE, 0.1 V·s⁻¹) under air of [L₅²(OH)Fe(OTf)](OTf) (red trace) and [L₅²(OMe)Fe(OTf)](OTf) (blue trace).</figcaption></figure>

The potential gain observed in the classical binding mode is understandable as the electron input into the Fe⁰/II/O₂ adduct is expected to generate an Fe³⁺-OO⁻ species in the 1st step. The presence of a hydrogen bond donor able to interact with the nascent anionic peroxo ligand would stabilize the species and thus favor the activation process.

In the case of the alternative mode, this potential gain is more puzzling as the OH group, located in the equatorial plane, cannot directly interact with the bound peroxo. Several hypotheses can be proposed to rationalize this observation (Scheme 6): i) the involvement of residual water molecules as relays between the equatorial OH group and the bound peroxo, ii) the decoordination of the hydroxypyridine upon oxidation, as this ligand becomes more labile in the absence of intramolecular hydrogen bond. The peroxo species could then be stabilized by H-bonding to the dangling 2-pyridone, iii) H bonding occurs intermolecularly, between the Fe³⁺-OO⁻ group of one complex and the bound
hydroxypyridine group of another. The latter is supported by the X-ray structure of [(L₅²(OH)Fe(OTf))(OTf)] in which the bound hydroxypyridine generates an intermolecular hydrogen bond with the triflate counterion (Figure 1).

<figure><img src="image_14.png" /><figcaption>**Scheme 6.** Proposed interpretation for the hydrogen bonding networks' involvement in the reductive O₂ activation taking place in the classical and alternative binding modes of L₅²(OH).</figcaption></figure>

The fact that the potential gain is even larger in the alternative mode than in the classical mode is at first counter-intuitive. However, whereas the OH group in the classical mode is structurally constrained to interact only with the proximal O in an end-on bound FeIII-peroxo species, the hydrogen-bonding pattern is much more flexible in the alternative mode. In hypothesis i) involving a water relay, a hydrogen bonding network involving not only the proximal, but also the distal O atom of an end-on bound FeIII-peroxo species can also be considered. In hypothesis ii), decoordination allows the dangling 2-pyridone to hydrogen bond to the distal O atom. Finally, in hypothesis iii), bulkiness will favor the H bonding interaction with the distal O atom as well (Scheme 6).

As a negative charge develops on this distal O atom upon electron input in the FeII/O₂ adduct, the FeIII-peroxo species would be better stabilized in the latter case, hence a better potential gain in the alternative binding mode case.

## Electroassisted oxidation of thioanisole

In the case of reference complex [(TPEN)FeII](PF₆)₂, the prewave for the activation of O₂ was overlapping with the reduction wave of free dioxygen. As a consequence, the energetic cost of the activation of O₂ was not significantly reduced by the presence of the complex, and the reduction of the Fe/O₂ adduct to yield a potentially active FeIII-peroxo was also accompanied by the generation of free superoxide with uncontrollable reactivity. In the case of [L₅²(OH)FeII(OTf)](OTf), the prewave is significantly shifted to more positive potentials (energetic gain) and it is fully extracted from the reduction wave of free O₂, so no free superoxide is generated at this potential. We thus attempted the electroassisted oxidation of a substrate (thioanisole), using reductive activation of O₂ by [L₅²(OH)FeII(OTf)](OTf), since we expect to generate *in situ* and transiently a metal-controlled oxidizing species. For this purpose, we carried out electrolysis of an aerated solution of thioanisole (800 mM) and [L₅²(OH)FeII(OTf)](OTf) (1.62 mM) at the potential of the prewave (-0.5 V vs SCE) for 2 hours. Over the time of the experiment, around 2 electrons per Fe are injected (Figures S39 & S40, Table S2). At the end of the electrolysis and after removal of the electrolyte and complex, the solution was analyzed by GC. The chromatogram shows a peak corresponding to the sulfoxide product, corresponding to a concentration of 0.24 ± 0.03 mM (Figure S44). Control experiments when the complex is absent, show no formation of sulfoxide. Also, when commercial FeII(OTf)₂ is used instead of the catalyst, only 0.03 mM of sulfoxide is obtained (Figure S43, Table S2).

Sulfone is also detected in the chromatogram for the runs and controls, but in the same quantities as the traces present in the commercial thioanisole substrate (Figures S43-S47, Table S3). It can be concluded that no sulfone is obtained by reductive activation of O₂ and that the sulfoxide product is not obtained by the reduction of the traces of sulfone present in the substrate. Assuming a 2-electron activation of O₂ is involved in the oxidation of thioanisole according to equation (ii), a faradaic yield of 16.2 ± 3.2 % can be estimated.

$$O_2 + 2e^- + 2H^+ + S \rightarrow H_2O + S=O \quad (ii)$$

We attempted to increase the reaction yield by addition of a source of protons (2,2,2-trifluoroethanol, 200 equiv. vs Fe). While the overall charge increases from around 1.7 to 3.5 C, the yield in sulfoxide product is not affected, suggesting that the extra electrons injected in solution are lost for the oxidation reaction (Figure S47, Table S2). This could be due to a "decoupling" phenomenon, well-known in natural systems,[2] between the reductive activation of O₂ and the oxidation of the substrate that can occur when protons induce the decoordination of a peroxo moiety from iron by release of H₂O₂, or even the subsequent reduction of the peroxo to water.

## Conclusion

We report the synthesis of a new pentadentate ligand L₅²(OH) bearing a 2-pyridone moiety. Upon coordination to iron, 2-pyridone isomerizes to 2-hydroxypyridine, generating a 2nd-sphere hydrogen-bond donor. L₅²(OH) can display two binding modes for iron: a classical one, which is displayed by all the pentadentate aminopyridine ligands that are parent of L₅²(OH) and an alternative one. We showed that each binding mode can be
selectively obtained by a judicious choice of the metal salt, as a
result of a subtle interplay between the bulkiness of the bound
counterion and the hydrogen bond ability and bulkiness of the 2-
hydroxypyridine moiety. In the classical binding mode, 2-
hydroxypyridine lies in an axial plane and its OH group can be
hydrogen-bonded to the exogenous ligand. In the alternative
mode, it is in the equatorial plane and this intramolecular
hydrogen-bond pattern vanishes, but can occur intermolecularly
instead.

In all cases, the addition of the H-bond donor on the ligand backbone significantly improves the reductive activation of O₂ by an iron complex: in the classical mode, it represents a 90-mV gain on the reduction potential, while in the alternative mode we achieve gains of up to 220 mV. Compared to the uncatalyzed activation (reduction of free O₂ at -1 V vs SCE), it represents a remarkable gain of 350 and 500 mV respectively.

We took advantage of this significant potential gain to attempt the electroassisted oxidation of a substrate. This allowed us to achieve the oxidation of thioanisole to methylphenyl sulfoxide at -0.5 V vs SCE using $[L_5^{2(OH)}Fe^{II}(OTf)](OTf)$, with faradaic yields of around 16 %.

We recently reported the ability to obtain an important gain in the
activation potential by tuning the donating ability of the ligand
backbone.[27] Together with the present results, this shows that a
rational bioinspired strategy allows to considerably reduce the
energetic cost of electroassisted oxidation processes. In the
future, we plan to combine these “push” and “pull” effects within
one single scaffold to further optimize the energetic efficiency of
complexes for both O₂ activation and the oxidation of substrates.

Supporting Information

Synthetic procedures, spectroscopic characterization and
analysis. The authors have cited additional references within the
Supporting Information. [28, 60-64]

Acknowledgements

This work was supported by the Agence Nationale de la
Recherche (GOAL Project, ANR-22-CE07-0037-01).

Keywords: non-heme iron complex • O₂ activation • thioanisole oxidation • 2nd sphere • pull effect

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