Development of a Highly Selective Ni(II) Chelator in Aqueous Solution.

The design, synthesis, and characterization of a novel Ni(II) chelator SG-20 is reported. SG-20 is selective in binding to Ni(II) versus other metal ions including Cu(II), Fe(II), Co(II), and Zn(II). At pH = 7.1, SG-20 binds Ni(II) with a Kd = 7.0 ± 0.4 µM. Job analysis indicates that SG-20 binds to both Ni(II) and Cu(II) with a 1:1 stoichiometry. Affinity of SG-20 for Ni(II) is pH dependent and decreases upon lowering to pH 4.0. A green solid was isolated from the reaction of SG-20 with NiCl2·6H2O in MeOH and characterized by X-ray photoelectron spectroscopy (XPS), electronic absorption and infrared (IR) spectroscopies, and mass spectrometry. Collectively, XPS and IR analysis revealed Ni-N and Ni-O interactions and a shift in C-O asymmetric and symmetric stretches consistent with Ni binding. Attempts to crystalize a mononuclear complex were unsuccessful, likely due to the Ni-SG-20 complex being in equilibrium with higher order species in solution. However, reaction of SG-20 with NiCl2·6H2O in water followed by slow evaporation yielded green crystals that were characterized by electronic absorption spectroscopy (λmax = 260 nm) and X-ray crystallography. These analyses revealed that SG-20 supports formation of a complex cluster containing six SG-20 ligands, 15 Ni(II), and three Na(I) centers, with two distinct types of Ni atoms in its outer and inner core. The nine Ni atoms present in the inner core were bound by oxo and carbonate bridges, whereas the six Ni atoms present in its outer shell were bound to N, O, and S donor atoms derived from SG-20. Overall, X-ray crystallographic analysis revealed that two chelator arms of SG-20 bind to one Ni(II) ion with an axial aqua ligand, whereas the third arm is free to interact with Ni ions within the central cluster, supporting the goal of Ni capture.

Heteroleptic Copper(I)-Based Complexes Incorporating BINAP and π-Extended Diimines: Synthesis, Catalysis and Biological Applications.

A series of copper-based photocatalysts of the type Cu(NN)(BINAP)BF4 were synthesized bearing π-extended diimine ligands. Their behavior in several photocatalytic processes were evaluated and revealed acceptable levels of activity in an SET process, but negligible activity in PCET or ET processes. Suitable activity in ET processes could be restored through modification of the ligand. The BINAP-derived complexes were then evaluated for activity against triple-negative breast cancer cell lines. Controls indicated that copper complexes, and not their ligands, were responsible for activity. Encouraging activity was displayed by a homoleptic complex Cu(dppz)2BF4.

The effect of four different intracanal medicaments on the push-out bond strength of root canal sealers.

This study aimed to compare the effect of 4 different intracanal medicaments on the push-out bond strength of two sealers (AH Plus and MTA Fillapex). 100 single-rooted extracted premolar teeth were divided into 5 groups, with 20 samples in each group, one group being the control group. After cleaning and shaping procedures, the canals were filled with 4 different medicaments: calcium hydroxide, tri-antibiotic paste (TAP), Metapex, or Chlorhexidine (2%) gel for 2 weeks. Following this, the medicaments were rinsed away, and the samples in those sub-groups were obturated with gutta-percha/AH Plus or MTA Fillapex sealers. After 2 weeks of incubation, a 2-mm-thick middle section from each root was evaluated to test push-out strength. The obtained data were tabulated, and appropriate statistical analysis was performed (two-way ANOVA and LSD test). When comparing the average values, the bond strength values of AH Plus were significantly higher than those of MTA Fillapex (p<0.05) in all medicament groups. Based on the findings, we concluded that AH Plus had comparatively higher bond strength than MTA Fillapex. We also observed that AH Plus had higher bond strength in the presence of calcium hydroxide, whereas MTA Fillapex in the presence of Chlorhexidine. A comparison of the push-out bond strength shows that irrespective of the root canal segment or the final irrigant used, AH Plus showed higher values among all groups. The limitation of the current study was that the effect of TAP on the bond strength of endodontic sealers was not negative.

Photocytotoxicity and photoinduced phosphine ligand exchange in a Ru(ii) polypyridyl complex.

Two new tris-heteroleptic Ru(ii) complexes with triphenylphosphine (PPh3) coordination, cis-[Ru(phen)2(PPh3)(CH3CN)]2+ (1a, phen = 1,10-phenanthroline) and cis-[Ru(biq)(phen)(PPh3)(CH3CN)]2+ (2a, biq = 2,2'-biquinoline), were synthesized and characterized for photochemotherapeutic applications. Upon absorption of visible light, 1a exchanges a CH3CN ligand for a solvent water molecule. Surprisingly, the steady-state irradiation of 2a followed by electronic absorption and NMR spectroscopies reveals the photosubstitution of the PPh3 ligand. Phosphine photoinduced ligand exchange with visible light from a Ru(ii) polypyridyl complex has not previously been reported, and calculations reveal that it results from a trans-type influence in the excited state. Complexes 1a and 2a are not toxic against the triple negative breast cancer cell line MDA-MB-231 in the dark, but upon irradiation with blue light, the activity of both complexes increases by factors of >4.2 and 5.8, respectively. Experiments with PPh3 alone show that the phototoxicity observed for 2a does not arise from the released phosphine ligand, indicating the role of the photochemically generated ruthenium aqua complex on the biological activity. These complexes represent a new design motif for the selective release of PPh3 and CH3CN for use in photochemotherapy.

MnII/III and CeIII/IV Units Supported on an Octahedral Molecular Nanoparticle of CeO2.

The preparation of three new heterometallic clusters [Ce6Mn12O17(O2CPh)26] (1), [Ce10Mn14O24(O2CPh)32] (2), and [Ce23Mn20O48(OH)2(tbb)46(H2O)4](NO3)2 (3; tbb- = 4-tBu-benzoate) is reported. They all possess unprecedented structures with a common feature being the presence of an octahedral CeIV-oxo core: a Ce6 in 1, two edge-fused Ce6 giving a Ce10 bioctahedron in 2, or a larger Ce19 octahedron in 3. Complex 1 is the first Ce6 cluster with a central µ6-O2-. 2 and the cation of 3 are molecular nanoparticles of CeO2 (ceria) because they possess the fluorite structure of bulk ceria and are thus ultrasmall ceria nanoparticles in molecular form. The {Ce19O32} octahedral subunit of the cation of 3 had been predicted from density functional theory studies to be one of the stable fragments of the CeO2 lattice, but has never been previously synthesized in molecular chemistry. Around the Ce/O core of 1-3 is an incomplete monolayer of Mnn ions disposed as four Mn3, two Mn7, and four Mn5 units, respectively. This represents a clear structural similarity with composite (phase-separated) CeO2/MnOx mixtures where at high Ce:Mn ratios the Mn atoms segregate on the surface of CeO2 phases. Variable-temperature dc and ac magnetic susceptibility studies have revealed S = 2, S = 1/2, and S = 3/2 ground states for 1-3, respectively. Fitting of the 5.0-300 K dc data for 1 to a two-J model for an asymmetrical V-shaped Mn3 unit with no interaction between the end MnIII ions gave an excellent fit with the following values: J1 = 5.2(3) cm-1, J2 = -7.4(3) cm-1, and g = 1.96(2).

Ru(II)-Based Acetylacetonate Complexes Induce Apoptosis Selectively in Cancer Cells.

The synthesis, chemical and biological characterization of seven Ru(II) polypyridyl complexes containing acetylacetonate (acac) ligands are reported. Electronic absorption spectra were determined and electrochemical potentials consistent with Ru(III/II) couples ranging from +0.60 to +0.73 V vs Ag/AgCl were measured. A series of complexes were screened against MDA-MB-231, DU-145, and MCF-10A cell lines to evaluate their cytotoxicities in cancer and normal cell lines. Although most complexes were either nontoxic or equipotent in cancer cells and normal cell lines, compound 1, [Ru(dpqy)(acac)(py)](PF6), where dqpy is 2,6-di(quinolin-2-yl)pyridine, showed up to 2.5:1.0 selectivity for cancer as compared to normal cells, along with nanomolar EC50 values in MDA-MB-231 cells. Lipophilicity, determined as the octanol/water partition coefficient, log Po/w, ranged from -0.33 (0.06) to 1.15 (0.10) for the complexes. Although cytotoxicity was not correlated with electrochemical potentials, a moderate linear correlation between lipophilicity and toxicities was observed. Cell death mechanism studies indicated that several of the Ru-acac compounds, including 1, induce apoptosis in MDA-MB-231 cells.

Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex.

A series of five ruthenium complexes containing triphenyl phosphine groups known to enhance both cellular penetration and photoinduced ligand exchange, cis-[Ru(bpy)2(P(p-R-Ph)3)(CH3CN)]2+, where bpy = 2,2'-bipyridine and P(p-R-Ph)3 represent para-substituted triphenylphosphine ligands with R = -OCH3 (1), -CH3 (2) -H (3), -F (4), and -CF3 (5), were synthesized and characterized. The photolysis of 1-5 in water with visible light (λ irr ≥ 395 nm) results in the substitution of the coordinated acetonitrile with a solvent molecule, generating the corresponding aqua complex as the single photoproduct. A 3-fold variation in quantum yield was measured with 400 nm irradiation, Φ 400, where 1 is the most efficient with a Φ 400 = 0.076(2), and 5 the least photoactive complex, with Φ 400 = 0.026(2). This trend is unexpected based on the red-shifted metal-to-ligand charge transfer (MLCT) absorption of 1 as compared to that of 5, but can be correlated to the substituent Hammett para parameters and pK a values of the ancillary phosphine ligands. Complexes 1-5 are not toxic towards the triple negative breast cancer cell line MDA-MB-231 in the dark, but 3 and 5 are >4.2 and >19-fold more cytotoxic upon irradiation with blue light, respectively. A number of experiments point to apoptosis, and not to necrosis or necroptosis, as the mechanism of cell death by 5 upon irradiation. These findings provide a foundation for understanding the role of phosphine ligands on photoinduced ligand substitution and show the enhancement afforded by -CF3 groups on photochemotherapy, which will aid the future design of photocages for photochemotherapeutic drug delivery.

Long-Range Ferromagnetic Exchange Interactions Mediated by Mn-CeIV-Mn Superexchange Involving Empty 4f Orbitals.

Reactions involving reductive aggregation of MnO4- in methanol in the presence of CeIV and an excess of carboxylic acid have led to the synthesis of structurally related Ce/Mn clusters, [Ce3Mn5O8(OMe)(O2CBut)13(MeOH)] (1) and [Ce2Mn3O5(O2CPh)9(MeOH)3] (2), containing at least one {Mn2Ce2O4} cubane unit. The cores of both clusters contain Mnx units separated by three (1) or two (2) CeIV ions. Fits of variable-temperature, solid-state dc and ac magnetic susceptibility data reveal dominant ferromagnetic interactions within 1 and 2, resulting in the maximum S = 17/2 and S = 5 ground state spins, respectively, and thus suggesting significant ferromagnetic (F) interactions between the Mnx units that are ≥6 Å apart and separated by four intervening bonds through diamagnetic CeIV. Fits of magnetic susceptibility data also revealed unusual long-range F interactions, and this finding was further supported by high-field EPR measurements and simulations. Density functional theory calculations and a Wannier function analysis confirm long-range interactions and indicate a Mn-Ce-Mn superexchange pathway via Mn-d/Ce-f orbital overlap/hybridization.

Structural and Magnetic Variations in a Family of Isoskeletal, Oximate-Bridged {MnIV2 MIII } Complexes (MIII =Mn, Gd, Dy).

The self-assembly reaction of MnCl2 ⋅4H2 O, acenaphthenequinone dioxime (acndH2 ) and NEt3 has yielded an unprecedented, linear {MnIV2 MnIII } complex with an S=5 spin ground state and non-SMM behavior. The targeted replacement of the central MnIII ion with GdIII and DyIII ions has successfully increased the S and turned on the SMM dynamics without affecting the core structure and the nature of the magnetic exchange interactions.

Structural Diversities in Heterometallic Mn-Ca Cluster Chemistry from the Use of Salicylhydroxamic Acid: {MnIII4Ca2}, {MnII/III6Ca2}, {MnIII/IV8Ca}, and {MnIII8Ca2} Complexes with Relevance to Both High- and Low-Valent States of the Oxygen-Evolving Complex.

One-pot reactions between the [Mn3O(O2CPh)6(py)x]+/0 triangular precursors and either CaBr2·xH2O or CaCl2·6H2O, in the presence of salicylhydroxamic acid (shaH2), have afforded the heterometallic complexes [MnIII4Ca2(O2CPh)4(shi)4(H2O)3(Me2CO)] (1) and (pyH)[MnII2MnIII4Ca2Cl2(O2CPh)7(shi)4(py)4] (2), respectively, in good yields. Further reactions but using a more flexible synthetic scheme comprising the Mn(NO3)2·4H2O/Ca(NO3)2·4H2O and Mn(O2CPh)2·2H2O/Ca(ClO4)2·4H2O "metal blends" and shaH2, in the presence of external base NEt3, led to the new complexes (NHEt3)2[MnIII4MnIV4Ca(OEt)2(shi)10(EtOH)2] (3) and (NHEt3)4[MnIII8Ca2(CO3)4(shi)8] (4), respectively. In all reported compounds, the anion of the tetradentate (N,O,O,O)-chelating/bridging ligand salicylhydroxime (shi3-), resulting from the in situ metal-ion-assisted amide-iminol tautomerism of shaH2, was found to bridge both Mn and Ca atoms. Complexes 1-4 exhibit a variety of different structures, metal stoichiometries, and Mn oxidation-state descriptions; 1 possesses an overall octahedral metal arrangement, 2 can be described as a Mn4Ca2 octahedron bound to an additional Mn2 unit, 3 consists of a Mn8 "ring" surrounding a CaII atom, and 4 adopts a rectangular cuboidal motif of eight Mn atoms accommodating two CaII atoms. Solid-state direct-current magnetic susceptibility studies revealed the presence of predominant antiferromagnetic exchange interactions between the Mn centers, leading to S = 0 spin ground-state values for all complexes. From a bioinorganic chemistry perspective, the reported compounds may demonstrate some relevance to both high-valent scheme (3) and lower-oxidation-level species (1, 2, and 4) of the catalytic cycle of the oxygen-evolving complex.

Synthesis and magnetochemistry of heterometallic triangular FeLnIII (Ln = La, Gd, Tb, Dy, and Ho) and FeYIII complexes.

A series of Fe2Ln (Ln = La, Gd, Tb, Dy and Ho) and Fe2Y complexes have been synthesized via metal substitution and characterized by single crystal X-ray diffraction. All the molecules are isostructural and have a Fe2LnO triangular core with the oxygen atom existing as an µ3-oxo2- anion. DC and AC magnetic susceptibility studies were performed on all the molecules. For Fe2Ln (Ln = Gd, La) and Fe2Y, the data were fitted to Van Vleck equations and the magnetic coupling constants were obtained. In all cases, the two Fe(iii) spins were found to be antiparallel to each other in the ground state leaving the heterometal to remain essentially uncoupled.