Tunable intramolecular multicenter H-bonding interactions in first-row metal complexes bearing bidentate redox-active ligands

Abstract

In this research article, we report the synthesis and structural characterization of a family of first-row metal complexes bearing redox-active ligands with tunable H-bonding donors. We observed that these coordination complexes can adopt three different geometries and that they are stabilized by intramolecular multicenter H-bonding interactions, which are systematically modified by changing the metal ion (Co, Ni, Cu, Zn), the ligand scaffold (variations in the diamine and ureanyl substituents used) and the solvent of crystallization.

Graphical Abstract

1. Introduction

Metalloenzymes promote an array of essential biological functions including biosynthesis, electron transfer and oxygen transport [1, 2]. In the active center of these natural catalysts, a metal ion is bound by natural ligands, which sometimes provide or accept electrons during catalysis. The secondary coordination sphere of the active center is molded by non-covalent interactions, usually H-bonds, that tune the reactivity of these metal complexes by enhancing substrate selectivity, enforcing rigidity for fast electron transfer or favoring certain reaction pathways (e.g. homolytic vs. heterolytic O–O bond cleavage). A paradigmatic example is cytochrome P450, a heme metalloenzyme involved in various challenging oxidations such as hydroxylation of unactivated hydrocarbons and epoxidation of olefins [3, 4]. It is proposed that during catalytic turnover, a hemecysteine moiety reduces O₂ in the presence of the substrate to form an iron(III)-hydroperoxide intermediate (Cmpd 0) before undergoing heterolytic O–O bond cleavage to generate a very reactive iron(IV)-oxo π-cation radical (Figure 1) [5, 6]. It is suggested that the secondary coordination sphere plays a critical role in delivering H⁺ at the right time and at the right place to facilitate this reductive O–O cleavage.

Figure 1.

Role of H-bonding in the heterolytic O–O bond cleavage in cytochrome P450.

Metal-dependent enzymes have inspired inorganic chemists to develop model systems capable of reproducing the structure, spectroscopy and reactivity of their active centers [7–9]. Over the last decades, understanding of how changes in the primary coordination sphere affect the reactivity of 3d metal complexes has advanced immensely [10, 11]. Rational and systematic design of the secondary coordination sphere has been more challenging and less investigated [12, 13]. The Borovik lab has pioneered the development of metal complexes that feature intramolecular H-bonding interactions [14]. The trianionic form of the H₆buea ligand scaffold (tris[(N′-tert-butylureayl)-N-ethylene]amine) has been used to synthesize mononuclear iron and manganese metal-(hydro)oxo complexes (Figure 2, left) [15–17]. The isolation of these intermediates at ambient temperature is rare due to the tendency of high-valent metal-oxo(hydroxo) complexes to be reduced and produce dimers, which is believed to be prevented by the strong H-bonding interactions between the ligand scaffold and the M-oxo(hydroxo) moiety. Interestingly, the bidentate version of this ligand sys-tem (H₄buea) was utilized to stabilize a dicobalt(III) bis-μ-oxo complex at room temperature [18, 19].

Figure 2.

High-valent metal-(hydro)oxo complexes stabilized by intramolecular H-bonding interactions.

We recently reported a family of copper complexes bearing bidentate redox-active ligands with tunable H-bonding donors (Figure 3) [20]. The crystal structures of the complexes revealed intramolecular multicenter H-bonding interactions between the ureanyl H-donors and the other ligand and/or metal ion. The copper complexes were found to stabilize five distinct oxidation states via reduction of the Cu^II center and by oxidation of the dianionic redox-active ligand scaffolds (L²⁻) to their imino-radical (L⁻) and bisimino forms (L). Some of the copper complexes were used as catalysts for the aerobic dehydrogenation of alcohols at room temperature. Our detailed mechanistic analysis suggested that oxidation of the substrate occurred via an unusual reaction pathway for galactose–oxidase model systems in which both dioxygen and ligand scaffold accept electrons and protons from the substrate simultaneously (note: in galactose oxidase, the reduction of O₂ and the oxidation of the substrate are two separate processes in a so-called “ping-pong” mechanism) [21]. In this research article, we analyze the coordination chemistry of a family of metal complexes, including other first-row transition metals than Cu (Co, Ni, Zn), in which the intramolecular multicenter H-bonding interactions can be tuned by ligand modification (i.e. changes in diamine backbone and ureanyl substituents) and crystallization conditions.

Figure 3.

Copper complexes bearing redox-active ligands with tunable H-bonding groups.

2. Results and discussion

2.1. Synthesis of ligands

The bidentate ligands were synthesized by mixing the corresponding diamine with two equivalents of isocyanate (Figure 4) [19, 20]. In most cases, the ligands were isolated as white powders in good yields (see Supplementary Material for further details). ¹H-NMR analysis of ligands indicated that changes in the diamine backbone or the ureanyl substituent perturbed the electronic environment of ureanyl protons (Hα and Hα′). For ^tBuPhLH₂, the ¹H-NMR peaks corresponding to Hα and Hα′ are at 7.5 and 6. 3 ppm, respectively, while for ^PhPhLH₂ (same backbone as ^tBuPhLH₂ but with a different ureanyl substituent), the Hα and Hα′ NMR resonances shifted to 8.0 and 9.0 ppm, respectively, indicative of the electron-withdrawing nature of the Ph group in comparison with tBu. For ^tBuEtLH₂ (different backbone but same ureanyl substituent), the signals for Hα and Hα′ shifted to 5.7 and 5.6 ppm, respectively, which is also in agreement with the stronger donating ability of the 1,2-ethyldiamine compared to the 1,2-phenyldiamine backbone.

Figure 4.

Synthesis of ligands. Note: the synthesis and characterization of ^tBuPhLH₂, ^PhPhLH₂, ^(S)-MeBzLH₂, ^{tBu-4,5-Me2-Ph}LH₂, ^{Ph-4,5-Me2-Ph}LH₂ and ^PhEtLH₂ was previously described by our research group [20]. The synthesis of ^tBuEtLH₂ was reported by Borovik and coworkers [19].

2.2. Syntheses of metal complexes

The metal complexes were synthesized under anaerobic conditions in DMA (dimethylacetamide) by reacting 1 equiv of ligand with 2 equiv of KH followed by addition of 0.5 equiv of the metal source (Figure 5). The complexes were purified and isolated as crystals by layering diethyl ether into DMA or DMF (dimethylformamide) solutions of the metal complexes. These metal compounds were characterized by different means, including elemental analysis, single crystal X-ray crystallography, NMR (i.e. ¹H-NMR for diamagnetic complexes), UV-vis, and FT-IR (see complete characterizations in the Supplementary Material).

Figure 5.

Synthesis of metal complexes. Note: the synthesis and characterization of ^tBuPhCu^II, ^PhPhCu^II, ^(S)-MeBzCu^II, ^{tBu-4,5-Me2-Ph}Cu^II, ^{Ph-4,5-Me2-Ph}Cu^II, ^tBuEtCu^II, and ^PhEtCu^II was previously described by our research group [20]; the synthesis and characterization of ^tBuEtFe^II, ^tBuEtNi^II, and ^tBuEtZn^II was reported by Borovik and coworkers [19].

2.3. Single crystal X-ray crystallography analysis

Crystalline samples of the metal compounds were analyzed by single crystal X-ray crystallography (see Table 1 and Supplementary Material). We found that these complexes can adopt three different geometries, square-planar (D_4h), tetrahedral (T_d) or twisted pseudo-tetrahedral (D_2d) geometries depending on the metal, ligand and the solvent used in the crystallization (Figure 6) [1]. We observed H-bonding interactions between the ureanyl Hα′ and the Nα atoms of the other ligand and some weak interactions between the ureanyl Hα′ and the metal center in an intramolecular multicenter fashion [12, 22, 23].

Table 1.

Selected distances, twist angle, solvent of crystallization and geometry for the metal complexes described in this article.

Complexa,b	d(Nα…Hα′) (Å)	d(M…Hα′) (Å)	αTW (°)	Solv.	Geometry
tBuPhCuIIDMF	2.154(19)–2.204(19)	2.72(2)–2.80(2)	0	DMF	D4h
tBuPhCuIIDMA	2.19(3)–2.25(3)	2.60(2)–2.67(2)	45.9	DMA	D2d
AdPhCuII	2.166(17)–2.303(18)	2.777(19)–2.814(19)	0	DMA	D4h
PhPhCuIIDMF	2.137(16)–2.165(16)	2.677(17)–2.728(17)	0	DMF	D4h
PhPhCuIIDMA	2.140(18)–2.501(18)	2.56(2)–2.734(19)	56.4	DMA	D2d
4-MeO-PhPhCuII	2.121(19)–2.206(19)	2.64(2)–2.86(2)	0	DMF	D4h
4-Cl-PhPhCuII	2.132(19)–2.17(2)	2.71(2)–2.74(2)	0	DMF	D4h
2,6-Me2-PhPhCuII	2.16(2)	2.73(2)–2.82(3)	0	DMF	D4h
2,6-F2-PhPhCuII	2.128(17)–2.338(17)	2.556(18)–2.639(18)	52.7–57.6c	DMF	D2d
2,6-Cl2-PhPhCuIIDMF	2.249(17)–2.324(17)	2.586(18)–2.598(18)	58.0	DMF	D2d
2,6-Cl2-PhPhCuIIDMA	2.252(18)–2.33(2)	2.61(2)–2.68(2)	54.4	DMA	D2d
(S)-MeBzPhCuII	2.21(3)–2.33(3)	2.54(3)–2.63(3)	51.3	DMA	D2d
(R)-MeBzPhCuII	2.22(3)–2.34(3)	2.58(3)–2.67(3)	51.4	DMA	D2d
tBu-4,5-Me2-PhCuII	2.236(16)–2.279(16)	2.786(17)–2.835(17)	0	DMF	D4h
Ad-4,5-Me2-PhCuII	2.14(2)–2.19(2)	2.77(3)	0	DMA	D4h
Ph-4,5-Me2-PhCuIIDMF	2.13(2)–2.35(3)	2.46(4)–2.58(4)	51.5–57.6c	DMF	D2d
Ph-4,5-Me2-PhCuIIDMA	2.13(2)–2.35(3)	2.46(4) – 2.58(4)	57.8	DMA	D2d
tBuEtCuII	2.28(2)–2.63(2)	2.67(2)–2.78(2)	48.0	DMF	D2d
PhEtCuII	2.10(2)–2.32(2)	2.48(2)–2.70(2)	46.3–48.4c	DMF	D2d
PhPhCoII	2.477(18)–2.571(18)	2.500(19)–2.55(2)	88.2	DMA	Td
PhPhNiII	2.062(14)–2.103(14)	2.637(16)–2.693(16)	0	DMF	D4h
PhPhZnII	2.519(18)–2.585(18)	2.529(19)–2.55(2)	88.4	DMA	Td

^aTables with all the crystallographic data can be found in the Supplementary Material.

^bThe crystal structure of ^tBuPhCu^II, ^PhPhCu^II, ^(S)-MeBzCu^II, ^{tBu-4,5-Me2-Ph}Cu^II, ^{Ph-4,5-Me2-Ph}Cu^II, ^tBuEtCu^II, and ^PhEtCu^II was previously described by our research group [20].

^cComplex with two conformations.

Figure 6.

Intramolecular multicenter H bonding.

We found that these H-bonding interactions are dependent on the geometry of the complex: for square-planar complexes (twist-angle, α_TW = 0) short Nα…Hα′ (~2.1–2.3 Å) and long M…Hα′ distances (~2.3–2.9 Å) are found, which systematically varied to longer Nα…Hα′ (~2.3–2.8 Å) and shorter M…Hα′ (~2.6–2.9 Å) distances upon increase of the twist angle α_TW (Figure 6).

2.3.1. Effect of different metals on the geometry of the complexes

X-ray diffraction analysis of the Co, Ni, Cu, and Zn complexes bearing the same ligand scaffold ^PhPhL²⁻ revealed that the identity of the metal ion has a deep impact on the geometry of the complex (Figure 7). We found that ^PhPhCu^II_DMF and ^PhPhNi^II are both square-planar with short Nα…Hα′ distances (~2.1 Å) and long M…Hα′ distances (~2.7 Å). On the other hand, the analogous ^PhPhCo^II and ^PhPhZn^II systems are tetrahedral (α_TW=88°) with longer Nα…Hα′ distances (~2.6 Å) and slightly shorter M…Hα′ distances (~2.5 Å).

Figure 7.

Effect of the metal identity on the geometry of the metal complexes.

2.3.2. Effect of solvent of crystallization

X-ray diffraction analysis of the Cu complexes also revealed that these complexes can adopt two different geometries D_4h and D_2d (Figure 8). Strikingly, the geometry of ^tBuPhCu^II and ^PhPhCu^II seemed to be strongly dependent on the solvent of crystallization. For example, ^tBuPhCu^II_DMF and ^PhPhCu^II_DMF are orange crystals with D_4h geometry in DMF but crystallization in DMA led to purple crystals with D_2d geometry (^tBuPhCu^II_DMA and ^PhPhCu^II_DMA).

Figure 8.

Effect of the solvent of crystallization on the geometry of the copper complexes.

In general, we observed that DMF tends to stabilize D_4h geometries while DMA produces D_2d complexes, but some exceptions can be found. For example, the Cu complexes bearing ligand scaffolds with adamantyl groups in the ureanyl substituent (^AdPhCu^II and ^{Ad-4,5-Me2-Ph}Cu^II) were crystallized in DMA and in both cases, a D_4h geometry was observed. Other complexes such as ^{Ph-4,5-Me2-Ph}Cu^II and ^2,6-Cl2-PhPhCu^II adopted the D_2d geometry in both solvents with comparable M-Nα, Nα…Hα′, M…Hα′ distances and similar twist angles. We analyzed the crystal structures and found that the potassium counterion played a critical role in stabilizing the different geometries (Figure 9). We observed that for the Cu complexes adopting D_4h geometry, the potassium ions were coordinated to the two O atoms of the ureanyl substituents (i.e. each K⁺ coordinated to two O atoms of the same ligand). On the other hand, the Cu complexes that adopted D_2d geometry were coordinated only by one potassium ion per ligand scaffold. We found that in both situations, either DMF or DMA are also coordinated to K⁺ but that DMF seems to favor the D_4h arrangement and DMA the D_2d.

Figure 9.

Effect of the solvent of crystallization on the geometry of the copper complexes.

2.3.3. Effect of the dimane backbone

We also observed that the geometry of the copper complexes depended on the diamine backbone utilized (Figure 10). The Cu^II complexes with the more flexible ethylenediamine backbone (^tBuEtL²⁻ and ^PhEtL²⁻) stabilize D_2d geometries. On the other hand, the more rigid o-phenylenediamine backbones (^tBuPhL²⁻ and ^PhPhL²⁻ in Figure 10) favor the formation of D_4h structures.

Figure 10.

Effect of the dimaine backbone on the geometry of the copper complexes.

2.3.4. Effect of the ureanyl substituent

Small changes in the structure of the ligands also led to a change in the geometry from D_4h to D_2d: ^2,6-Cl2-PhPhCu^II, ^2,6-F2-PhPhCu^II, and ^2,6-Me2-PhPhCu^II were all crystallized in DMF but only the latter had a D_4h geometry (Figure 11). Like in the other examples described above, the ^2,6-Me2-PhPhCu^II D4h structure showed shorter Nα…Hα′ distances (~2.2 Å) and longer M…Hα′ distances (~2.8 Å) when compared to the ^2,6-Cl2-PhPhCu^II and ^2,6-F2-PhPhCu^II D_2d structures (Nα…Hα′ distances ~2.3 Å; M…Hα′ distances ~2.6 Å).

Figure 11.

Effect of the ureanyl substituents on the geometry of the copper complexes.

2.3.5. Intramolecular multicenter hydrogen bonds, general trends

With all the structural information in hand, we plotted the M–Hα′ distances against the Nα…Hα′ distances (Figure 12) [22] and found that the metal complexes adopting square-planar geometry (D_4h, α_TW=0°) were clustered at the top left of the chart, which illustrates their short Nα…Hα′ and long M…Hα′ distances (area marked in orange). A second group of complexes comprising the Cu compounds with twisted pseudo-tetrahedral geometry (D_2d, 40° < α_TW < 60°) can also be identified, which show slightly shorter M…Hα′ distances and longer Nα…Hα′ (marked in red). A third group of compounds includes the Co^II and Zn^II complexes with geometries close to tetrahedral (α_TW~90°) in which the Nα…Hα′ and M…Hα′ distances are very similar (area marked in grey in Figure 12). We also noticed that within the D_4h and D_2d groups of metal complexes (marked in orange and red), most of the data points form linear correlations, in which an increase of the N…Hα′ leads to a proportional increase of the M…Hα′ (slope ~ 1).

Figure 12.

Scattegram in which average Nα…Hα′ distances are plotted against average M…Hα′ distances. Note: the X-ray diffraction analysis of ^tBuPhCu^II, ^PhPhCu^II, ^(S)-MeBzCu^II, ^{tBu-4,5-Me2-Ph}Cu^II, ^{Ph-4,5-Me2-Ph}Cu^II, ^tBuEtCu^II, and ^PhEtCu^II was previously described by our research group [20].

From the structural analysis of this family of metal complexes (22 crystal structures included in this work and the ^tBuEtFe^II, ^tBuEtNi^II, ^tBuEtCo^II, and ^tBuEtZn^II structures previously reported by Borovik [19]) we can extract some general trends. First, Cu^II and Ni^II favor square-planar (D_4h) and distorted tetrahedral geometries (D_2d) and the rest of the metals favor tetrahedral (T_d) geometry [19]. Second, for the Cu complexes, the D_2d geometry is generally favored with DMA as the crystallization solvent and the D_4h geometry is favored when DMF is used as solvent of crystallization, although some exceptions can be found (e.g. D_4h ^{Ad-4-5-Me2-Ph}Cu^II was obtained in DMA). Third, for the Cu^II complexes, the more flexible ethylenediamine backbone (e.g. ^tBuEtL²⁻ and ^PhEtL²⁻) favors D_2d geometries while the more rigid o-phenylenediamine (e.g. ^tBuPhL²⁻and ^PhPhL²⁻) favors stabilization of D_4h structures.

3. Conclusions and perspectives

In this work, we described the synthesis and structural characterization of metal complexes bound by bidentate redox-active ligands with tunable H-bonds. We found that these complexes were stabilized via intramolecular multicenter H-bonding interactions between the ligands and the metal center, and that the directionality of these interactions depended on the geometry of the complexes. The ability of the Cu complexes to adopt at least two coordination environments suggests that these intramolecular H-bonding interactions are flexible and able to rearrange and stabilize different geometries, which we believe plays a critical role in the catalytic oxidation of alcohols (i.e. we proposed that H-bonding interactions are able to stabilize a reactive Cu/O₂ species and to direct the coordination of substrate prior to C–H oxidation).

Our current efforts are focused on expanding this family of complexes in terms of metals used (more examples of Fe, Co, Ni, Zn), ligands (diamine and ureanyl variations) and crystallization conditions (solvent, counterions, etc.). We believe that all of this structural information will allow us to predict the geometry and H-bonding interactions upon modification of the metal complex systems. To the best of our knowledge, this is one of the first research articles in which intramolecular H-bonding interactions are systematically varied and analyzed. Ongoing studies are focused on analyzing the impact of these changes on the reactivity and spectroscopy of these complexes. We are also interested in quantifying, experimentally and/or theoretically, the strength of these intramolecular multicenter H-bonding interactions [24].