Spectroscopic and Magnetic Studies of Co(II) Scorpionate Complexes: Is There a Halide Effect on Magnetic Anisotropy?

The observation of single-molecule magnetism in transition-metal complexes relies on the phenomenon of zero-field splitting (ZFS), which arises from the interplay of spin-orbit coupling (SOC) with ligand-field-induced symmetry lowering. Previous studies have demonstrated that the magnitude of ZFS in complexes with 3d metal ions is sometimes enhanced through coordination with heavy halide ligands (Br and I) that possess large free-atom SOC constants. In this study, we systematically probe this "heavy-atom effect" in high-spin cobalt(II)-halide complexes supported by substituted hydrotris(pyrazol-1-yl)borate ligands (TptBu,Me and TpPh,Me). Two series of complexes were prepared: [CoIIX(TptBu,Me)] (1-X; X = F, Cl, Br, and I) and [CoIIX(TpPh,Me)(HpzPh,Me)] (2-X; X = Cl, Br, and I), where HpzPh,Me is a monodentate pyrazole ligand. Examination with dc magnetometry, high-frequency and -field electron paramagnetic resonance, and far-infrared magnetic spectroscopy yielded axial (D) and rhombic (E) ZFS parameters for each complex. With the exception of 1-F, complexes in the four-coordinate 1-X series exhibit positive D-values between 10 and 13 cm-1, with no dependence on halide size. The five-coordinate 2-X series exhibit large and negative D-values between -60 and -90 cm-1. Interpretation of the magnetic parameters with the aid of ligand-field theory and ab initio calculations elucidated the roles of molecular geometry, ligand-field effects, and metal-ligand covalency in controlling the magnitude of ZFS in cobalt-halide complexes.

Reversible Dioxygen Binding to Co(II) Complexes with Noninnocent Ligands.

A series of mononuclear Co(II) complexes with noninnocent (redox-active) ligands are prepared that exhibit metal-ligand cooperativity during the reversible binding of O2. The complexes have the general formula, [CoII(LS,N)(TpR2)] (R = Me, Ph), where LS,N is a bidentate o-aminothiophenolate and TpR2 is a hydrotris(pyrazol-1-yl)borate scorpionate with R-substituents at the 3- and 5-positions. Exposure to O2 at room temperature results in one-electron oxidation and deprotonation of LS,N. The oxidized derivatives possess substantial "singlet diradical" character arising from antiferromagnetic coupling between an iminothiosemiquinonate (ITSQ•-) ligand radical and a low-spin Co(II) ion. The [CoII(TpMe2)(X2ITSQ)] complexes, where X = H or tBu, coordinate O2 reversibly at reduced temperatures to provide Co/O2 adducts. The O2 binding reactions closely resemble those previously reported by our group (Kumar et al., J. Am. Chem. Soc. 2019,141, 10984-10987) for the related complexes [CoII(TpMe2)(tBu2SQ)] and [CoII(TpMe2)(tBu2ISQ)], where tBu2(I)SQ represents 4,6-di-tert-butyl-(2-imino)semiquinonate radicals. In each case, the oxygenation reaction proceeds via the addition of O2 to both the cobalt ion and the ligand radical, generating metallocyclic cobalt(III)-alkylperoxo structures. Thermodynamic measurements elucidate the relationship between O2 affinity and redox potentials of the (imino)(thio)semiquinonate radicals, as well as energetic differences between these reactions and conventional metal-based oxygenations. The results highlight the utility and versatility of noninnocent ligands in the design of O2-absorbing compounds.

Design, Synthesis, Electronic Properties, and X-ray Structural Characterization of Various Modified Electron-Rich Calixarene Derivatives and Their Conversion to Stable Cation Radical Salts.

We have designed and synthesized electron-rich calixarene derivatives, which undergo reversible electrochemical oxidation in a well-accessible potential range that allows the ready preparation and isolation of the corresponding cation radicals. Preparation of mono- or tetra-radical cation can be achieved by using stable aromatic cation-radical salts such as MA+•, MB+•, and NAP+• as selective organic oxidants. The cation radicals of calixarenes are stable indefinitely at ambient temperatures and can be readily characterized by UV-vis-NIR spectroscopy. These cation radicals bind a single molecule of nitric oxide within its cavity with remarkable efficiency.

Regioselectivity in the Scholl Reaction: Mono and Double [7]Helicenes.

We employed the density functionaly theory (DFT)-predicted regioselectivity of the intramolecular Scholl reaction in phenanthrene and dibenzo[g,p]chrysene frameworks to obtain π-extended mono and double [7]helicenes, respectively. The formation of these helical structures occurs despite the buildup of a large strain energy up to 30 kcal/mol compared with their most stable isomers. The twisted and strained structures were characterized and analyzed by experimental (NMR, UV-vis, emission, electrochemistry, and single-crystal X-ray diffraction) techniques and were further supported by DFT calculations.

Probing the Magnetic Anisotropy of Co(II) Complexes Featuring Redox-Active Ligands.

Coordination complexes that possess large magnetic anisotropy (otherwise known as zero-field splitting, ZFS) have possible applications in the field of magnetic materials, including single molecule magnets (SMMs). Previous studies have explored the role of coordination number and geometry in controlling the magnetic anisotropy and SMM behavior of high-spin (S = 3/2) Co(II) complexes. Building upon these efforts, the present work examines the impact of ligand oxidation state and structural distortions on the spin states and ZFS parameters of pentacoordinate Co(II) complexes. The five complexes included in this study (1-5) have the general formula, [Co(TpPh2)(LX,Y)]n+ (X = O, S; Y = N, O; n = 0 or 1), where TpPh2 is the scorpionate ligand hydrotris(3,5-diphenyl-pyrazolyl)borate(1-) and LX,Y are bidentate dioxolene-type ligands that can access multiple oxidation states. The specific LX,Y ligands used herein are 4,6-di-tert-butyl substituted o-aminophenolate and o-aminothiophenolate (1 and 2, respectively), o-iminosemiquinonate and o-semiquinonate radicals (3 and 4, respectively), and o-iminobenzoquinone (5). Each complex exhibits a distorted trigonal bipyramidal geometry, as revealed by single-crystal X-ray diffraction. Direct current (dc) magnetic susceptibility experiments confirmed that the complexes with closed-shell ligands (1, 2, and 5) possess S = 3/2 ground states with negative D-values (easy-axis anisotropy) of -41, -78, and -30 cm-1, respectively. For 3 and 4, antiferromagnetic coupling between the Co(II) center and o-(imino)semiquinonate radical ligand results in S = 1 ground states that likewise exhibit very large and negative anisotropy (-100 > D > -140 cm-1). Notably, ZFS was measured directly for each complex using far-infrared magnetic spectroscopy (FIRMS). In combination with high-frequency and -field electron paramagnetic resonance (HFEPR) studies, these techniques provided precise spin-Hamiltonian parameters for complexes 1, 2, and 5. Multireference ab initio calculations, using the CASSCF/NEVPT2 approach, indicate that the strongly negative anisotropies of these Co(II) complexes arise primarily from distortions in the equatorial plane due to constrictions imposed by the TpPh2 ligand. This effect is further amplified by cobalt(II)-radical exchange interactions in 3 and 4.

Nonheme iron-thiolate complexes as structural models of sulfoxide synthase active sites.

Two mononuclear iron(ii)-thiolate complexes have been prepared that represent structural models of the nonheme iron enzymes EgtB and OvoA, which catalyze the O2-dependent formation of carbon-sulfur bonds in the biosynthesis of thiohistidine compounds. The series of Fe(ii) complexes reported here feature tripodal N4 chelates (LA and LB) that contain both pyridyl and imidazolyl donors (LA = (1H-imidazol-4-yl)-N,N-bis((pyridin-2-yl)methyl)methanamine; LB = N,N-bis((1-methylimidazol-2-yl)methyl)-2-pyridylmethylamine). Further coordination with monodentate aromatic or aliphatic thiolate ligands yielded the five-coordinate, high-spin Fe(ii) complexes [FeII(LA)(SMes)]BPh4 (1) and [FeII(LB)(SCy)]BPh4 (2), where SMes = 2,4,6-trimethylthiophenolate and SCy = cyclohexanethiolate. X-ray crystal structures revealed that 1 and 2 possess trigonal bipyramidal geometries formed by the N4S ligand set. In each case, the thiolate ligand is positioned cis to an imidazole donor, replicating the arrangement of Cys- and His-based substrates in the active site of EgtB. The geometric and electronic structures of 1 and 2 were analyzed with UV-vis absorption and Mössbauer spectroscopies in tandem with density functional theory (DFT) calculations. Exposure of 1 and 2 to nitric oxide (NO) yielded six-coordinate FeNO adducts that were characterized with infrared and electron paramagnetic resonance (EPR) spectroscopies, confirming that these complexes are capable of binding diatomic molecules. Reaction of 1 and 2 with O2 causes oxidation of the thiolate ligands to disulfide products. The implications of these results for the development of functional models of EgtB and OvoA are discussed.

Route exploration and synthesis of the reported pyridone-based PDI inhibitor STK076545.

The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported ß-keto-amide with an N-alkylated pyridone at the α-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an α-pyridone allyl ester as a key step. An X-ray crystal structure of the final compound confirmed that the reported structure of STK076545 was achieved, however its lack of PDI activity and inconsistent spectral data suggest that the commercial structure was misassigned.

Modified Synthesis of the Peptidomimetic Natriuretic Peptide Receptor-C Antagonist M372049.

The Natriuretic Peptide Receptors (NPRs) regulate vascular sodium levels and have been of significant interest for the potential treatment of hypertension and related cardiovascular complications. The peptidomimetic antagonist M372049 is a valuable probe for the study of NPR-C signaling, unfortunately it is presently not commercially available. Described is a detailed protocol for its synthesis that does not require specialized apparatus and builds upon a prior patent from Veale and colleagues. Key steps include a base-mediated lactam formation and a solid-supported peptide synthetic sequence. An X-ray crystal structure of a key lactam intermediate was obtained to confirm the structure and relative stereochemistry of the compound.

Angular ladder-type meta-phenylenes: synthesis and electronic structural analysis.

Herein, we report the synthesis of two new series of angular (all-syn) ladder-type meta-[n]phenylenes (LMP, n = 3-8). One series contains keto groups at the termini bridges, denoted angular keto (AKn), the second contains alkyl groups at all bridge sp3 carbons, denoted angular alkyl (AAn). Their electronic and structural properties were delineated by a combination of electrochemistry and spectroscopic (UV-Vis and emission) methods and further supported by DFT calculations. Interestingly, experimental and DFT data show that changing the bridging group at the termini from alkyl (AAn) to keto (AKn) gives an increase in the first reduction potentials and LUMO energies, as the π-system is extended. Also, the charge (de)localization behavior is different for these two species; while the AAn compounds stablize charge with Robin-Day class III, the AKn compounds show a clear switch from class III to class II. In comparison with the linear analogues (LKn and LAn), DFT results reveal a shape independency of the charge (de)localization mechanism in acceptor-π-acceptor series (AKn/LKn).

Spectroscopic and Computational Comparisons of Thiolate-Ligated Ferric Nonheme Complexes to Cysteine Dioxygenase: Second-Sphere Effects on Substrate (Analogue) Positioning.

Parallel spectroscopic and computational studies of iron(III) cysteine dioxygenase (CDO) and synthetic models are presented. The synthetic complexes utilize the ligand tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (Ph2TIP), which mimics the facial three-histidine triad of CDO and other thiol dioxygenases. In addition to the previously reported [FeII(CysOEt)(Ph2TIP)]BPh4 (1; CysOEt is the ethyl ester of anionic l-cysteine), the formation and crystallographic characterization of [FeII(2-MTS)(Ph2TIP)]BPh4 (2) is reported, where the methyl 2-thiosalicylate anion (2-MTS) resembles the substrate of 3-mercaptopropionate dioxygenase (MDO). One-electron chemical oxidation of 1 and 2 yields ferric species that bind cyanide and azide anions, which have been used as spectroscopic probes of O2 binding in prior studies of FeIII-CDO. The six-coordinate FeIII-CN and FeIII-N3 adducts are examined with UV-vis absorption, electron paramagnetic resonance (EPR), and resonance Raman (rRaman) spectroscopies. In addition, UV-vis and rRaman studies of cysteine- and cyanide-bound FeIII-CDO are reported for both the wild-type (WT) enzyme and C93G variant, which lacks the Cys-Tyr cross-link that is present in the second coordination sphere of the WT active site. Density functional theory (DFT) and ab initio calculations are employed to provide geometric and electronic structure descriptions of the synthetic and enzymatic FeIII adducts. In particular, it is shown that the complete active space self-consistent field (CASSCF) method, in tandem with n-electron valence state second-order perturbation theory (NEVPT2), is capable of elucidating the structural basis of subtle shifts in EPR g values for low-spin FeIII species.

Iron(ii) tetrafluoroborate complexes of new tetradentate C-scorpionates as catalysts for the oxidative cleavage of trans-stilbene with H2O2.

Attachment of a 2-methylpyridyl group onto the unique 1-nitrogen atom on nitrogen-confused C-scorpionates with either pyrazol-1-yl or 3,5 dimethylpyrazol-1-yl donors gives two new cis-directing tetradentate-N4 ligands (L and L*). The complexes [(L or L*)Fe(CH3CN)2](BF4)2 (1 or 2) were prepared, fully characterized, and investigated for their ability to catalyse the oxidative cleaveage of trans-stilbene in CH3CN. Complexes 1 and 2 are capable of catalysing stilbene cleavage when H2O2 is used as an oxidant but up to six different products are formed, with C[double bond, length as m-dash]C cleavage products (benzaldehyde and benzoic acid) dominating over four products of oxygen transfer. Catalytic amounts of 1 or 2 enhance the ability for the organic photocatalyst riboflavin tetraacetate to use atmospheric oxygen and blue light irradation (450-460 nm) to selectively cleave stilbene to benzaldehyde. However, when benzaldehyde oxidizes further to benzoic acid, the iron species begin giving increasing amounts of stilbene oxygenation products.

Redox-Induced Molecular Actuators: The Case of Oxy-Alternate Bridged Cyclotetraveratrylene.

We report a practical two-step approach for the synthesis of hybrid-bridge macrocyclic molecules that has been used to synthesize two novel oxy-alternate-bridged macrocyclic molecules, oxy-alternate cyclotetraveratrylene (O-altCTTV) and oxy-alternate cyclohexaveratrylene (O-altCHV). Electrochemistry, absorption spectroscopy, X-ray crystallography, and DFT calculations demonstrate that O-altCTTV acts as a redox-induced molecular actuator, as its switches from the open conformation in the neutral state to the closed conformation in the cation-radical state.

Cobalt Superoxo and Alkylperoxo Complexes Derived from Reaction of Ring-Cleaving Dioxygenase Models with O2.

The syntheses and O2 reactivities of active-site models of cobalt-substituted ring-cleaving dioxygenases are presented. The pentacoordinate cobalt(II)-aminophenolate complex, [Co(TpMe2)(tBu2APH)], gives rise to two distinct dioxygen adducts at reduced temperatures. The first is a paramagnetic (S = 1/2) cobalt(III)-superoxo species that was characterized with spectroscopic and computational techniques. The identity of the second Co/O2 adduct was elucidated by X-ray crystallography, which revealed an unprecedented cobalt(III)-alkylperoxo structure generated by O2 addition to the metal ion and ligand. These results provide synthetic precedents for proposed intermediates in the catalytic cycles of O2-activating cobalt enzymes.

Selective Isomer Formation and Crystallization-Directed Magnetic Behavior in Nitrogen-Confused C-Scorpionate Complexes of Fe(O3SCF3)2.

The complex [Fe(HL*)2](OTf)2, 1, where HL* = bis(3,5-dimethylpyrazol-1-yl)(3-1H-pyrazole)methane, was prepared in order to compare its magnetic properties with those of the analogous parent complex, [Fe(HL)2](OTf)2, that lacks methyl groups on pyrazolyl rings and that undergoes spin crossover (SCO) from the low spin (LS) to the high spin (HS) form above room temperature. It was anticipated that this new semibulky derivative should favor the HS state and undergo SCO at a lower temperature range. During this study, six crystalline forms of 1 were prepared by controlling the crystallization conditions. Thus, when reagents are combined in CH3CN, an equilibrium mixture of cis and trans isomers is established that favors the latter below 311 K. The trans isomer can be isolated exclusively as a mixture of solvates, LS trans-1·2CH3CN and HS trans-1·4CH3CN, by cooling CH3CN solutions to -20 °C with the former being favored at high concentrations and short crystallization times. Subsequently, vapor diffusion of Et2O into CH3CN solutions of pure trans-1·2CH3CN gives solvate-free HS trans-1. Subjecting trans-1·2CH3CN to vacuum at room temperature gives microcrystalline trans-1·CH3CN, identified by elemental analysis and its distinct powder X-ray diffraction pattern. If an isomeric mixture of 1 is subject to room-temperature vapor diffusion, then a crystalline mixture of HS isomers cis-1 and trans-1 is obtained. Finally, slowly cooling hot acetonitrile solutions of isomeric mixtures of 1 to room temperature gives large prisms of HS co-1, a species with both cis and trans isomers in the unit cell. The complexes trans-1, trans-1·CH3CN, cis-1, and co-1 undergo SCO below 250 K while trans-1·xCH3CN (x = 2, 4) solvates do not undergo SCO before desolvation.

Calix[4]arene-Based Bis(Nitric Oxide) Complexes: Synthesis, Physical Properties, and Structural Characterization.

Calix[4]arene-based molecules hold great promise as candidate sensors and storage materials for nitric oxide (NO), owing to their unprecedented binding affinity for NO. However, the structure of calix[4]arene is complicated by the availability of four possible conformers: 1,3-alternate, 1,2-alternate, cone, and partial cone (paco). Whilst complexes of NO with several of these conformers have previously been established, the 1,2-alternate conformer complex, that is, [1,2-alter⋅NO]+ , has not been previously reported. Herein, we determine the crystal structure of the NO complex with the 1,2-alternate conformer for the first time. In addition, we have also found that the 1,2-alternate and 1,3-alternate conformers can combine with two NO molecules to form stable bis(nitric oxide) complexes. These new complexes, which exhibit remarkable binding capacity for the construction of NO-storage molecules, were characterized by using X-ray crystallography and NMR, IR, and UV/Vis spectroscopy. These findings will extend our understanding of the interactions between nitric oxide and cofacially and non-cofacially arrayed aromatic rings, and we expect them to aid in the design and development of new supramolecular sensors and storage materials for NO with high capacity and efficacy.

Highly Selective Synthesis of Pillar[ n]arene ( n = 5, 6).

An efficient and highly selective synthetic method toward the preparation of pillar[ n]arenes ( n = 5, 6) is reported, based upon a high solvent-dependent selectivity found in the condensation reaction between 1,4-dialkyloxybenzene and paraformaldehyde, involving methanesulfonic acid as catalyst. Pillar[6]arene (P6) is obtained as the major product when using chloroform as solvent, while in dichloromethane pillar[5]arene (P5) is the dominant product. Accordingly, a series of P5 and P6 have been selectively synthesized with excellent yield.

A synthetic model of the nonheme iron-superoxo intermediate of cysteine dioxygenase.

A nonheme Fe(ii) complex (1) that models substrate-bound cysteine dioxygenase (CDO) reacts with O2 at -80 °C to yield a purple intermediate (2). Analysis with spectroscopic and computational methods determined that 2 features a thiolate-ligated Fe(iii) center bound to a superoxide radical, mimicking the putative structure of a key CDO intermediate.

Molecular Actuators in Action: Electron-Transfer-Induced Conformation Transformation in Cofacially Arrayed Polyfluorenes.

There is much current interest in the design of molecular actuators, which undergo reversible, controlled motion in response to an external stimulus (light, heat, oxidation, etc.). Here we describe the design and synthesis of a series of cofacially arrayed polyfluorenes (MeF nH m) with varied end-capping groups, which undergo redox-controlled electromechanical actuation. Such cofacially arrayed polyfluorenes are a model molecular scaffold to investigate fundamental processes of charge and energy transfer across a π-stacked assembly, and we show with the aid of NMR and optical spectroscopies, X-ray crystallography and DFT calculations that in the neutral state the conformation of MeF nH1 and MeF nH2 is open rather than cofacial, with a conformational dependence that is highly influenced by the local environment. Upon (electro)chemical oxidation, these systems undergo a reversible transformation into a closed fully π-stacked conformation, driven by charge-resonance stabilization of the cationic charge. These findings are expected to aid the design of novel wire-like cofacially arrayed systems capable of undergo redox-controlled actuation.

Synthesis of Doubly Annulated m-Terphenyl-Based Molecular Tweezers and Their Charge-Transfer Complexes with DDQ as a Guest.

The synthesis of a doubly-annulated m-terphenyl-based tweezer platform has been developed, which affords ready incorporation of various pincer units from monobenzenoid to polybenzenoid electron donors. The complexation study with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as guest has been carried out, and the crystal structure of T-Py∩DDQ reveals the sandwich-type binding mode in the solid state.

An electron-transfer induced conformational transformation: from non-cofacial "sofa" to cofacial "boat" in cyclotetraveratrylene (CTTV) and formation of charge transfer complexes.

Electro-active polychromophoric assemblies that undergo clam-like electromechanic actuation represent an important class of organic functional materials. Here, we show that the readily available cyclotetraveratrylene (CTTV) undergoes oxidation-induced folding, consistent with interconversion from a non-cofacial "sofa" conformation to a cofacial "boat" conformer. It is found that the non-cofacial "sofa" conformer of CTTV forms stable electron donor-acceptor complexes with chloranil and DDQ. Electron-transfer induced conformational transformation in CTTV provides a framework for the rational design of novel organic functional molecules.