Spectroscopic and Theoretical Investigation of High-Spin Square-Planar and Trigonal Fe(II) Complexes Supported by Fluorinated Alkoxides.

The electronic structures and spectroscopic behavior of three high-spin FeII complexes of fluorinated alkoxides were studied: square-planar {K(DME)2}2[Fe(pinF)2] (S) and quasi square-planar {K(C222)}2[Fe(pinF)2] (S') and trigonal-planar {K(18C6)}[Fe(OC4F9)3] (T) where pinF = perfluoropinacolate and OC4F9 = tris-perfluoro-t-butoxide. The zero-field splitting (ZFS) and hyperfine structure parameters of the S = 2 ground states were determined using field-dependent 57Fe Mössbauer and high-field and -frequency electron paramagnetic resonance (HFEPR) spectroscopies. The spin Hamiltonian parameters were analyzed with crystal field theory and corroborated by density functional theory (DFT) and ab initio complete active space self-consistent field (CASSCF) calculations. Whereas the ZFS tensor of S has a small rhombicity, E/D = 0.082, and a positive D = 15.17 cm-1, T exhibits a negative D = -9.16 cm-1 and a large rhombicity, E/D = 0.246. Computational investigation of the structural factors suggests that the ground-state electronic configuration and geometry of T's Fe site are determined by the interaction of [Fe(OC4F9)3]- with {K(18C6)}+. In contrast, two distinct countercations of S/S' have a negligible influence on their [Fe(pinF)2]2- moieties. Instead, the distortions in S' are likely induced by the chelate ring conformation change from δλ, observed for S, to the δδ conformation, determined for S'.

Enzyme Control Over Ferric Iron Magnetostructural Properties.

Fe3+ complexes in aqueous solution can exist as discrete mononuclear species or multinuclear magnetically coupled species. Stimuli-driven change to Fe3+ speciation represents a powerful mechanistic basis for magnetic resonance sensor technology, but ligand design strategies to exert precision control of aqueous Fe3+ magnetostructural properties are entirely underexplored. In pursuit of this objective, we rationally designed a ligand to strongly favor a dinuclear µ-oxo-bridged and antiferromagnetically coupled complex, but which undergoes carboxylesterase mediated transformation to a mononuclear high-spin Fe3+ chelate resulting in substantial T1 -relaxivity increase. The data communicated demonstrate proof of concept for a novel and effective strategy to exert biochemical control over aqueous Fe3+ magnetic, structural, and relaxometric properties.

Cytotoxic Naphthoquinone Analogues, Including Heterodimers, and Their Structure Elucidation Using LR-HSQMBC NMR Experiments.

Approximately 1700 naphthoquinones have been reported from a range of natural product source materials, but only 283 have been isolated from fungi, fewer than 75 of those were dimers, and only 2 were heterodimers with a head-to-tail linkage. During a search for anticancer leads from fungi, a series of new naphthoquinones (1-4), including two heterodimers (3 and 4), were isolated from Pyrenochaetopsis sp. (strain MSX63693). In addition, the previously reported 5-hydroxy-6-(1-hydroxyethyl)-2,7-dimethoxy-1,4-naphthalenedione (5), misakimycin (6), 5-hydroxy-6-[1-(acetyloxy)ethyl]-2,7-dimethoxy-1,4-naphthalenedione (7), 6-ethyl-2,7-dimethoxyjuglone (8), and kirschsteinin (9) were isolated. While the structure elucidation of 1-9 was achieved using procedures common for natural products chemistry studies (high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D NMR), the elucidation of the heterodimers was facilitated substantially by data from the long-range heteronuclear single quantum multiple bond correlation (LR-HSQMBC) experiment. The absolute configuration of 1 was established by analysis of the measured vs calculated ECD data. The racemic mixture of 4 was established via X-ray crystallography of an analogue that incorporated a heavy atom. All compounds were evaluated for cytotoxicity against the human cancer cells lines MDA-MB-435 (melanoma), MDA-MB-231 (breast), and OVCAR3 (ovarian), where the IC50 values ranged between 1 and 20 µM.

Rational Ligand Design Enables pH Control over Aqueous Iron Magnetostructural Dynamics and Relaxometric Properties.

Complexes of Fe3+ engage in rich aqueous solution speciation chemistry in which discrete molecules can react with solvent water to form multinuclear µ-oxo and µ-hydroxide bridged species. Here we demonstrate how pH- and concentration-dependent equilibration between monomeric and µ-oxo-bridged dimeric Fe3+ complexes can be controlled through judicious ligand design. We purposed this chemistry to develop a first-in-class Fe3+-based MR imaging probe, Fe-PyCy2AI, that undergoes relaxivity change via pH-mediated control of monomer vs dimer speciation. The monomeric complex exists in a S = 5/2 configuration capable of inducing efficient T1-relaxation, whereas the antiferromagnetically coupled dimeric complex is a much weaker relaxation agent. The mechanisms underpinning the pH dependence on relaxivity were interrogated by using a combination of pH potentiometry, 1H and 17O relaxometry, electronic absorption spectroscopy, bulk magnetic susceptibility, electron paramagnetic resonance spectroscopy, and X-ray crystallography measurements. Taken together, the data demonstrate that PyCy2AI forms a ternary complex with high-spin Fe3+ and a rapidly exchanging water coligand, [Fe(PyCy2AI)(H2O)]+ (ML), which can deprotonate to form the high-spin complex [Fe(PyCy2AI)(OH)] (ML(OH)). Under titration conditions of 7 mM Fe complex, water coligand deprotonation occurs with an apparent pKa 6.46. Complex ML(OH) dimerizes to form the antiferromagnetically coupled dimeric complex [(Fe(PyCy2AI))2O] ((ML)2O) with an association constant (Ka) of 5.3 ± 2.2 mM-1. The relaxivity of the monomeric complexes are between 7- and 18-fold greater than the antiferromagnetically coupled dimer at applied field strengths ranging between 1.4 and 11.7 T. ML(OH) and (ML)2O interconvert rapidly within the pH 6.0-7.4 range that is relevant to human pathophysiology, resulting in substantial observed relaxivity change. Controlling Fe3+ µ-oxo bridging interactions through rational ligand design and in response to local chemical environment offers a robust mechanism for biochemically responsive MR signal modulation.

Heterotrimetallic {LnOVPt} complexes with antiferromagnetic Ln-V coupling and magnetic memory.

The new PtVO(SOCR)4 lantern complexes, 1 (R = CH3) and 2 (R = Ph) behave as neutral O-donor ligands to Ln(OR)3 with Ln = Ce, Nd. Four heterotrimetallic complexes with linear {LnOVPt} units were prepared: [Ln(ODtbp)3{PtVO(SOCR)4}] (Ln = Ce, 3Ce (R = CH3), 4Ce (R = Ph); Nd, 3Nd (R = CH3), 4Nd (R = Ph); ODtbp = 2,6-ditertbutylphenolate). Magnetic characterization confirms slow magnetic relaxation behaviour and suggests antiferromagnetic coupling across {Ln-O[double bond, length as m-dash]V} in all four complexes, with variations tunable as a function of Ln and R.

Meroterpenoids from Neosetophoma sp.: A Dioxa[4.3.3]propellane Ring System, Potent Cytotoxicity, and Prolific Expression.

Six fungal metabolites, of which five were new, including one (1) with a dioxa[4.3.3]propellane ring system, were discovered, identified, and structurally elucidated from Neosetophoma sp. (strain MSX50044); these compounds are similar to the bis-tropolone, eupenifeldin. Three of the meroterpenoids are potent cytotoxic agents against breast, ovarian, mesothelioma, and lung cancer cells with nanomolar IC50 values while not inducing mitochondrial toxicity at 12.5 µM.

Square-planar Co(iii) in {O4} coordination: large ZFS and reactivity with ROS.

Oxidation of distorted square-planar perfluoropinacolate Co compound [CoII(pinF)2]2-, 1, to [CoIII(pinF)2]1-, 2, is reported. Rigidly square-planar 2 has an intermediate-spin, S = 1, ground state and very large zero-field splitting (ZFS) with D = 67.2 cm-1; |E| = 18.0 cm-1, (E/D = 0.27), g⊥ = 2.10, g‖ = 2.25 and χTIP = 1950 × 10-6 cm3 mol-1. This Co(iii) species, 2, reacts with ROS to oxidise two (pinF)2- ligands to form tetrahedral [CoII(Hpfa)4]2-, 3.

Pt-Mg, Pt-Ca, and Pt-Zn Lantern Complexes and Metal-Only Donor-Acceptor Interactions.

Pt-based heterobimetallic lantern complexes of the form [PtM(SOCR)4(L)] have been shown previously to form intermolecular metallophilic interactions and engage in antiferromagnetic coupling between lanterns having M atoms with open shell configurations. In order to understand better the influence of the carboxylate bridge and terminal ligand on the electronic structure, as well as the metal-metal interactions within each lantern unit, a series of diamagnetic lantern complexes, [PtMg(SAc)4(OH2)] (1), [PtMg(tba)4(OH2)] (2), [PtCa(tba)4(OH2)] (3), [PtZn(tba)4(OH2)] (4), and a mononuclear control (Ph4P)2[Pt(SAc)4] (5) have been synthesized. Crystallographic data show close Pt-M contacts enforced by the lantern structure in each dinuclear case. 195Pt-NMR spectroscopy of 1-4, (Ph4P)2[Pt(SAc)4] (5), and several previously reported lanterns revealed a strong chemical shift dependence on the identity of the second metal (M), mild influence by the thiocarboxylate ligand (SOCR; R = CH3 (thioacetate, SAc), C6H5 (thiobenzoate, tba)), and modest influence from the terminal ligand (L). Fluorescence spectroscopy has provided evidence for a Pt···Zn metallophilic interaction in [PtZn(SAc)4(OH2)], and computational studies demonstrate significant dative character. In all of 1-4, the short Pt-M distances suggest that metal-only Lewis donor (Pt)-Lewis acceptor (M) interactions could be present. DFT and NBO calculations, however, show that only the Zn examples have appreciable covalent character, whereas the Mg and Ca complexes are much more ionic.

Pt···Pt vs Pt···S contacts between Pt-containing heterobimetallic lantern complexes.

A trio of Pt-based heterobimetallic lantern complexes of the form [(py)PtM(SAc)4(py)] (M = Co, 1; Ni, 2; Zn, 3) with unusual octahedral coordination of Pt(II) was prepared from a reaction of [PtM(SAc)4] with excess pyridine. These dipyridine lantern complexes could be converted to monopyridine derivatives with gentle heat to give the series [PtM(SAc)4(py)] (M = Co, 4; Ni, 5; Zn, 6). An additional family of the form [PtM(SAc)4(pyNH2)] (M = Co, 7; Ni, 8; Zn, 9) was synthesized from reaction of [PtM(SAc)4(OH2)] or [PtM(SAc)4] with 4-aminopyridine. Dimethylsulfoxide and N,N-dimethylformamide were also determined to react with [PtM(SAc)4] (M = Co, Ni), respectively, to give [PtCo(SAc)4(DMSO)](DMSO), 10, and [PtNi(SAc)4(DMF)](DMF), 11. Structural and magnetic data for these compounds and those for two other previously published families, [PtM(tba)4(OH2)] and [PtM(SAc)4(L)], L = OH2, pyNO2, are used to divide the structures among three distinct categories based on Pt···Pt and Pt···S distances. In general, the weaker donors H2O and pyNO2 seem to favor metallophilicity and antiferromagnetic coupling between 3d metal centers. When Pt···S interactions are favored over Pt···Pt ones, no coupling is observed and the pKa of the pyridine donor correlates with the interlantern S···S distance. UV-vis-NIR electronic and (1)H NMR spectra provide complementary characterization as well.

Total synthesis and absolute stereochemical assignment of kibdelone C.

Kibdelones are hexacyclic tetrahydroxanthones and potent anticancer agents isolated from an Australian microbe. Herein, we describe the synthesis of a chiral, nonracemic iodocyclohexene carboxylate EF ring fragment of the kibdelones employing an intramolecular iodo halo-Michael aldol reaction and its merger with an ABCD ring fragment to afford the congener kibdelone C.

Catalytic Activation of H(2) and C-H Bonds by Electron-Deficient Ruthenium(II) Porphyrins.

The Ru(2) and RuNi derivatives of 1,8-bis(10,15,20-trimesityl-5-porphyrinato)anthracene-a recently reported cofacial diporphyrin ligand comprising two hindered porphyrins spanned by an anthracene bridge-have been synthesized. Both Ru(2)(DPAHM) and RuNi(DPAHM) are extremely reactive species that apparently contain 14-electron Ru(II) centers and, as is the case for their monoporphyrin analog, (5,10,15,20-tetramesitylporphyrinato)ruthenium [Ru(TMP)], must be rigorously protected from oxygen, nitrogen, and other ligating agents. In addition, these electron-deficient Ru(II) porphyrins all appear to bind aromatic solvents such as benzene and toluene, the weakest ligating solvents in which these Ru(II) porphyrins have been found soluble. Ru(TMP) and its metallodiporphyrin analogs, Ru(2)(DPAHM) and RuNi(DPAHM), catalyze H(2)/D(2) exchange in benzene solution and as solids. When adsorbed on a particularly nonpolar carbon support, these Ru(II) porphyrins all manifest significant activity with respect to catalytic H(2)/D(2) exchange [approximately 40 turnovers s(-)(1), when normalized for Ru(II) content]. In addition, these molecules slowly catalyze the exchange of H(2) into deuterated aromatic hydrocarbons and, in the absence of solvent, the exchange of D(2) into CH(4). Kinetic studies of H(2)/D(2) exchange catalyzed by these Ru(II) porphyrins on carbon supports indicate that exchange is likely to be effected by one face of a single Ru(TMP) moiety. The activity of each supported catalyst was suppressed by the presence of ligands, either exogenous (CO irreversibly and N(2) reversibly) or from polar functionalities on the surface of the supporting matrix.