Impact of steric bulk on photoinduced ligand exchange reactions in Mn(I) photoCORMs

Highlights

• NN ligand steric effects in fac-[Mn(NN)(CO)₃(L)]ⁿ⁺ photoCORMs were studied.

• Steric bulk from NN = 6,6′-Me₂bpy distorts the structure vs NN = 4,4′-Me₂bpy.

• Steric bulk enhances ligand dissociation efficiency with 405 nm irradiation.

• The bulky 6,6′-Me2bpy facilitates thermal release of py following first CO release.

• The steric demands of NN impact the formation of final photoproducts.

Abstract

The investigation of ligand exchange reactions in Mn(I)-based photoactivated CO-releasing molecules, or “photoCORMs,” has largely focused on the electronic effects of the ligand set. In this work, we report the effects of sterically bulky bidentate (NN) ligands on the efficiency for CO release and the formation of photochemical intermediates in fac-[Mn(NN)(CO)₃(L)]ⁿ⁺ photoCORMs. The vibrational and electronic absorption spectroscopy and photochemistry of two new Mn(I) photoCORMs with a sterically bulky 6,6′-dimethyl-2,2′-bipyridine ligand, fac-[Mn(6,6′-Me₂bpy)(CO)₃Br] (6,6′-Me₂bpy-Br) and fac-[Mn(6,6′-Me₂bpy)(CO)₃(py)]⁺ (6,6′-Me₂bpy-py), are reported in comparison to two previously reported analogues, fac-[Mn(4,4′-Me₂bpy)(CO)₃Br] (4,4′-Me₂bpy-Br) and fac-[Mn(4,4′-Me₂bpy)(CO)₃(py)]⁺ (4,4′-Me₂bpy-py) with the 4,4′-dimethyl-2,2′-bipyridine ligand. The steric demands of the methyl substituents in the 6,6′ positions on bpy significantly distort the structure, as the crystal structure shows contraction between the equatorial CO ligands and tilting of the bidentate ligand relative to the 4,4′-Me₂bpy complexes. The movement of the methyl substituents from the 4,4′ to the 6,6′ positions on bpy has little impact on the electronic properties of the complexes, as observed by FTIR and electronic absorption spectroscopy, while the steric bulk of 6,6′-Me₂bpy increases the quantum yield of CO release (Φ_CO) and increases the lability of the Br⁻ and py ligands compared to the 4,4′-Me₂bpy complexes with less steric bulk.

Introduction

Carbon monoxide is a gaseous molecule that participates in several cell signaling pathways. As a result, endogenously produced CO plays important physiological roles such as anti-inflammation, cytoprotection, vasodilation, and blood vessel formation [1], [2], [3], [4], [5], [6]. Recent research has also indicated therapeutic potential for CO, such as anti-bacterial and anti-cancer activity [3], [5], [7], [8], [9], [10]. At high concentrations, CO is anti-proliferative and pro-apoptotic in cancer cells, while it is anti-apoptotic and anti-inflammatory in healthy tissue [3]. Due to the toxicity and storage safety issues arising from inhalation of gaseous CO [11], delivery of the small molecule with high spatiotemporal control is an important goal. The tendency of CO to act as a Lewis base, forming coordinate covalent (or dative) bonds with transition metal ions, has enabled the development of CO-releasing molecules (termed “CORMs”), in which the CO is deactivated through formation of metal-CO bond [12], [13], [14]. Upon bond cleavage, the CO is released and its pharmacological activity is restored.

CORMs that release CO through photochemical bond dissociation are known as “photoCORMs,” or photo-activated CO-releasing molecules [15], [16], [17], [18], [19], [20], [21]. PhotoCORMs allow for CO to remain coordinated to a metal complex pro-drug until irradiation with UV or visible light at a desired location, such as a tumor or infection, releases one or more equivalents of CO. The wavelength required for bond cleavage and the number of CO molecules released per metal complex depend on the molecular architecture. While many photoCORMs have been reported featuring Fe, Ru, Cr, W, Mo, and Re [2], [15], [22], [23], [24], [25], [26], [27], [28], [29], those featuring Mn(I) have been increasingly studied due to their ability to release multiple equivalents of CO with visible light [7], [8], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], a desirable feature to decrease photoinduced damage to healthy cells and tissue [53].

A frequently studied architecture for Mn(I) photoCORMs is fac-[Mn(NN)(CO)₃(L)]ⁿ⁺, in which NN is typically a diimine bidentate ligand and L is a monodentate ancillary ligand such as Br⁻, CH₃CN, phosphines, or N-containing heterocycles. The identities of NN and L influence the photophysical properties and photochemical ligand dissociation. Excitation with visible light results in population of a lowest-lying metal-to-ligand charge transfer (MLCT) state, which may also have a significant amount of halide-to-ligand charge transfer (XLCT) character if L is a halide [15], [19]. The reduced electron density on the metal weakens the π-backbonding between Mn and CO ligands, allowing ligand dissociation. It is generally reported that the quantum yield for CO release (Φ_CO) increases as π-acidity of the bidentate ligand increases [15]. For example, in the set of fac-[Mn(NN)(CO)₃Br] compounds in which NN = (2-phenyliminomethyl)quinoline (pimq), 2-quinoline-N-(2′-methylthiophenyl)methyleneimine (qmtpm), and 2-pyridyl-N-(2′-methylthiophenyl)methyleneimine (pmtpm), the value for Φ_CO with 509 nm irradiation increases from NN = pimq to pmtpm to qmtpm as conjugation on the NN ligand increases [54].

The efficiency and rate of CO release are also influenced by the nature of the monodentate ancillary ligand L, as π-donor ligands tend to provide greater CO release efficiency compared to π-acceptor ligands. In the case of the fac-[Mn(qmtpm)(CO)₃L]ⁿ⁺ and fac-[Mn(pmtpm)(CO)₃L]ⁿ⁺ complexes, the CO release rate is greater when L = Br⁻ compared to L = CH₃CN [54]. The π-donor Br⁻ destabilizes the Mn(dπ) orbitals relative to the case when L is the π-acceptor CH₃CN, resulting in a lower energy MLCT state and enhanced absorptivity at longer wavelengths. Similarly, in photoCORMs with the fac-[Mn(azpy)(CO)₃(L)]ⁿ⁺ (azpy = 2-phenylazopyridine) architecture, the rate of CO release from the compound when L = Br⁻ is greater than the rate when L = PPh₃ [33], [34]. Monodentate ligands that coordinate through imidazolyl groups also increase the quantum yield for CO dissociation compared to those with piperazinyl groups, as observed in the fac-[Mn(phen)(CO)₃(L)]⁺ complexes, where phen = 1,10-phenanthroline and L = imidazoledanysl or 1-dansylpiperazine [39], [41].

Our previous work with fac-[Mn(NN)(CO)₃Br] and fac-[Mn(NN)(CO)₃(py)]⁺ photoCORMs, in which NN = 4,4′-dimethyl-2,2′-bipyridine (4,4′-Me₂bpy), 2,2′-bipyridine (bpy), and 4,4′-dimethylester-2,2′-bipyridine (4,4′-dmebpy), highlighted the strong influence of the monodentate L ligand in the photochemical ligand dissociation reactions [47]. We discovered that a π-donating Br⁻ directs photodissociation of an equatorial CO in the first step, while a π-accepting py directs photodissociation of the axial CO in the first step. We observed this trend regardless of the electron-donating (methyl) or electron-withdrawing (methyl ester) substituents at the 4,4′ positions of 2,2′-bipyridine. Additionally, in agreement with reports of related Mn(I) photoCORMs, the Φ_CO increases with increasing NN π-acidity (4,4′-Me₂bpy < bpy < 4,4′-dmebpy) in each series, and all compounds with L = Br⁻ displayed larger Φ_CO values than their L = py analogues.

The purpose of this work is to broaden our investigation by probing the impact of a sterically bulky NN bidentate ligand on the photochemical ligand dissociation efficiency and mechanism in fac-[Mn(NN)(CO)₃L]ⁿ⁺ photoCORMs. The impact of steric distortion on fac-[Mn(NN)(CO)₃L]ⁿ⁺ photoCORMs has not been clearly investigated. In this study, we utilized 6,6′-dimethyl-2,2′-bipyridine (6,6′-Me₂bpy) to prepare two new photoCORMs, fac-[Mn(6,6′-Me₂bpy)(CO)₃Br] (6,6′-Me₂bpy-Br) and fac-[Mn(6,6′-Me₂bpy)(CO)₃(py)]⁺ (6,6′-Me₂bpy-py) for direct comparison to our previously reported fac-[Mn(4,4′-Me₂bpy)(CO)₃Br] (4,4′-Me₂bpy-Br) and fac-[Mn(4,4′-Me₂bpy)(CO)₃(py)]⁺ (4,4′-Me₂bpy-py) analogues [47]. The photoCORMs discussed in this work are shown in Fig. 1. The methyl groups at the 4,4′- and 6,6′-positions are expected to impart similar electronic effects but significantly different steric effects as a result of the placement of the substituents relative to the Mn-CO bonds. Herein we present an investigation into the impact of steric bulk on the structure and photophysical and photochemical properties of fac-[Mn(NN)(CO)₃L]ⁿ⁺ photoCORMs.