Octadecylamine-Mediated Versatile Coating of CoFe₂O₄ NPs for the Sustained Release of Anti-Inflammatory Drug Naproxen and in Vivo Target Selectivity

Magnetic nanoparticles (MNPs) can play a distinct role in magnetic drug delivery via their distribution to the targeted area. The preparation of such MNPs is a challenging multiplex task that requires the optimization of size, magnetic, and surface properties for the achievement of desirable target selectivity, along with the sustained drug release as a prerequisite. In that context, CoFe2O4 MNPs with a small size of ∼7 nm and moderate saturation magnetization of ∼60 emu g–1 were solvothermally synthesized in the presence of octadecylamine (ODA) with a view to investigate the functionalization route effect on the drug release. Synthetic regulations allowed us to prepare MNPs with aminated (AmMNPs) and amine-free (FAmMNPs) surface. The addition of the nonsteroidal anti-inflammatory drug with a carboxylate donor, Naproxen (NAP), was achieved by direct coupling with the NH2 groups, rendered by ODA, through the formation of an amide bond in the case of AmMNPs. In the case of FAmMNPs, indirect coupling of NAP was performed through an intermediate linker (polyethylenimine) and on PEG-ylated MNPs. FT-IR, 1H NMR, 13C NMR, and UV–vis data confirmed the addition of NAP, whereas diverse drug-release behavior was observed for the different functionalization approaches. The biological behavior of the MNPs@NAP was evaluated in vitro in rat serum and in vivo in mice, after radiolabeling with a γ-emitting radionuclide, 99mTc. The in vivo fate of MNPs@NAP carriers was in straightforward relation with the direct or indirect coupling of NAP. Furthermore, an inflammation was induced intramuscularly, where the directly coupled 99mTc-MNPs@NAP carriers showed increased accumulation at the inflammation site

Unveiling the Physicochemical Features of CoFe₂O₄ Nanoparticles Synthesized via a Variant Hydrothermal Method: NMR Relaxometric Properties

A series of CoFe₂O₄ nanoparticles were formed through a variant hydrothermal synthesis based on a self-assembled oil–water system in autoclaves at 200 °C in the presence of octadecylamine and the trivalent iron and cobalt acetylacetonates. The variation of the water content, the different valence of the cobalt precursors (Co­(II) and Co­(III)) as well as Fe:Co precursor ratios (2:1 and 1:1) were studied. CoFe₂O₄ nanoparticles with a size range of 9–16 nm of high crystallinity and enhanced saturation magnetization (∼89 emu g^–1) have been isolated and characterized. Raman spectroscopy provided information concerning the lattice strain, while incorporation of Co²⁺ at T_d sites of the spinel indicated a different inversion degree (0.67–0.60) among the samples. EPR studies showed that EPR signal and spin relaxation process were size dependent and influenced by aggregation effects. CoFe₂O₄ nanoparticles were converted to dual agents via a reaction between the free amine groups of the organic coating and the sulfonyl group of the fluorescent dye sulforhodamine B acid chloride (SRB) and NMR relaxometric properties were measured. The relatively high transverse relaxivity values, <i>r</i>₂ (232.0–130.3 mM^–1 s^–1) were attributed to nanocluster effects in aqueous suspensions with respect with the amount of SRB and encourage their potential application as versatile agents in theranostics

From Monomer Zinc−Oxamato Complexes to Tetranuclear Inverse 12-Membered and Octanuclear 12-Membered Metallacrowns

Interaction of ZnCl2 with Hpko (Hpko, di-2-pyridyl-ketonoxime) results in the formation of a uninuclear Zn(Hpko)Cl2 (1) compound or in a 12-membered tetranuclear metallacrown (OH)2[inv12-MCZn(II)N(pko)-4]Cl2 (2) depending on the pH of the mother solution. The addition of H3shi (H3shi, salicylhydroxamic acid) leads to the formation of the octanuclear 12-membered tetranuclear metallacrown [Zn2]{[Zn2(pko)4][12-MCZn(II)N(shi)-4](CH3OH)2} (3). The metallacrown core of 2 is characterized as “inverse” because the zinc atoms, rather than oxygen atoms, are oriented toward the central cavity. Two triply bridging hydroxides are accommodated in the center of the metallacrown ring. The pko- ligands form a propeller configuration that imposes absolute stereoisomerism with Λ and Δ chirality. Each hydroxo oxygen bridges two octahedral zinc atoms and a tetrahedral one. The octanuclear cluster Zn8(shi)4(pko)4(CH3OH)2 contains a 12-membered tetranuclear metallacrown core constructed by four Zn metal atoms and four shi3- ligands. So, a part of the cluster can be described as having the formally anionic [12-MCZn(II)N(shi)-4]4- core. Two of the zinc atoms are in octahedral coordination environment while for the other two the geometry is best described as distorted trigonal bipyramidal. The metallacrown core accommodates a binuclear compound with the formula [Zn2(pko)4]. Two of the ring metal ions create binuclear units with two zinc ions, respectively, with two oxamato oxygens, and two phenolato oxygens, of the four interlinked shi3- ligands acting as bridging atoms

Interaction of ZnO Nanostructures with Proteins: In Vitro Fibrillation/Antifibrillation Studies and in Silico Molecular Docking Simulations

Protein amyloidosis is related to many neurological disorders. Nanoparticles (NPs) due to their small size can regulate both the polypeptide monomers/oligomers assembly into amyloid fibrils/plaques and the disintegration of the existent plaques. Herein, we have synthesized ZnO nanoflowers and polyol-coated ZnO NPs of relatively small size (40 nm) with cylindrical shape, through solvothermal and microwave-assisted routes, respectively. The effect of the different morphology of nanostructures on the fibrillation/antifibrillation process was monitored in bovine serum albumin (BSA) and human insulin (HI) by fluorescence Thioflavin T (ThT) measurements. Although both nanomaterials affected the amyloid formation mechanism as well as their disaggregation, ZnO nanoflowers with their sharp edges exhibited the greatest amyloid degradation rate in both model proteins (73% and 35%, respectively) and inhibited the most the insulin fibril growth, while restrained also the fibrillation process in the case of albumin solution. In silico molecular docking simulations on the crystal structure of BSA and HI were performed to analyze further the observed in vitro activity of ZnO nanostructures. The binding energy of ZnO NPs was found lower for BSA (−5.44), highlighting their ability to act as catalysts in the fibrillation process of albumin monomers

A Two-Dimensional Manganese(II) Carboxylato Polymer. Structure, Magnetism, and EPR Study

The synthesis, crystal structure, and properties of [MnII(MCPA)2(H2O)2]n (MCPA = 2-methyl-4-chlorophenoxyacetic acid), 1, a 2-D manganese carboxylato polymer is reported. The synthesis of 1 has been achieved via the reaction of MCPA with MnCl2·2H2O and NaHCO3 in methanol. Crystal structure data:  [C18H20Cl2O8Mn]; orthorhombic; space group Pbca; a = 7.811(6) Å; b = 34.67(3) Å; c = 7.481(6) Å; Z = 4. The compound has a two-dimensional structure with Mn2+ atoms in an octahedral environment and mixed water/carboxylate coordination. The metal atoms are segregated in planes which are perpendicular to the b axis and are spaced 17.73 Å apart. Variable-temperature magnetic susceptibility measurements indicate the presence of antiferromagnetic behavior. The EPR spectra of polycrystalline samples at 4 K show that the intensity of the signal decreases significantly with decreasing temperature and below ∼4 K becomes EPR silent

Structurally Diverse Copper(II)−Carboxylato Complexes: Neutral and Ionic Mononuclear Structures and a Novel Binuclear Structure

The copper complexes with the commercial auxin herbicides MCPA, 2,4-D, and 2,4,5-T in the presence of a nitrogen donor heterocyclic ligand, phen or bipyam, were prepared and characterized. The available evidence supports a dimeric structure for the 2,4-D complex in the presence of bipyam while phen leads to monomeric forms. The EPR spectrum of Cu2(2,4-D)4(bipyam)2 at 4 K in the solid state exhibits an axial signal which corresponds to almost isolated S = 1/2 magnetic ions. Magnetic data for the dimer show a weak antiferromagnetic interaction between the two metal ions with J = −0.8 cm-1. The crystal structures of tetrakis[(2,4-dichlorophenoxy)acetato]bis(2,2‘-bipyridylamine)dicopper(II), 1, bis(1,10-phenanthroline)[(2,4,5-trichlorophenoxy)acetato]copper(II) chloride, 2, and aqua(1,10-phenanthroline)bis[((2-methyl-4-chlorophenoxyacetato]copper(II), 3, were determined and refined by least-squares methods using three-dimensional MoKα data. 1 crystallizes in space group P1̄, in a cell of dimensions a = 10.813(1) Å, b = 12.138(1) Å, c = 11.909(1) Å, α = 86.448(3)°, β = 80.127(3)°, and γ = 63.982(3)°, and V = 1383.7(2) Å3, with Z = 1. 2 crystallizes in space group I2/a, in a cell of dimensions a = 29.958(9) Å, b = 11.342(3) Å, c = 21.196(7) Å, β = 107.94(1)°, and V = 6852.2(4) Å3, with Z = 8. 3 crystallizes in space group P1̄, in a cell of dimensions a = 8.7419(8) Å, b = 12.512(1) Å, c = 14.598(1) Å, α = 110.737(1)°, β = 95.742(2)°, γ = 103.286(2)°, V = 1424.1(2) Å3, with Z = 2

Multifunctional Polymeric Platform of Magnetic Ferrite Colloidal Superparticles for Luminescence, Imaging, and Hyperthermia Applications

Adequately designed multiresponsive water-soluble graft copolymers were used to serve as a multifunctional polymeric platform for the encapsulation and transfer in aqueous media of hydrophobic magnetic nanoparticles (MNPs). The backbone of the graft copolymers was composed of hydrophilic sodium methacrylate units, hydrophobic dodecyl methacrylate units, and luminescent quinoline-based units, while either the homopolymer poly­(N-isopropylacrylamide) or a poly­(N,N-dimethylacrylamide-co-N-isopropylacrylamide) copolymer was used as thermosensitive pendent side chains. The polymeric platform forms micellar-type assemblies in aqueous solution, and exhibits pH-responsive luminescent properties and a lower critical solution temperature behavior in water. Depending on the design of the side chains, the cloud point temperatures were determined at 38 and 42 °C, close or slightly above body temperature (37 °C). Above the critical micelle concentration (CMC), both graft copolymers can effectively stabilize in aqueous media as magnetic colloidal superparticles (MSPs), oleylamine-coated MnFe2O4 MNPs, as well as 1:1 mixture of oleylamine-coated MnFe2O4 and CoFe2O4 MNPs. When CoFe2O4 particles were mixed with MnFeO4 in equal amounts, the specific loss power increased significantly, while an opposite trend was observed in the magnetic resonance imaging (MRI) studies, probably due to the anisotropy of cobalt. As a consequence, fine-tuning of the chemical structure of the copolymers and the composition of the MSPs can lead to materials that are able to act simultaneously as luminescent, hyperthermia, and contrast MRI agents

Experimental and Theoretical Study of the Antisymmetric Magnetic Behavior of Copper <i>inverse</i>-9-Metallacrown-3 Compounds

Use of PhPyCNO−/X− “blends” (PhPyCNOH = phenyl 2-pyridyl ketoxime; X− = OH−, alkanoato, ClO4−) in copper chemistry yielded trinuclear clusters that have been characterized as inverse-9-metallacrown-3 compounds and accommodate one or two guest ligands. The magnetic behavior showed a large antiferromagnetic interaction and a discrepancy between the low-temperature magnetic behavior observed experimentally and that predicted from a magnetic model. The discrepancy between the Brillouin curve and the experimental result provides clear evidence of the influence of the antisymmetric interaction. Introducing the antisymmetric terms derived from the fit of the susceptibility data into the magnetization formula caused the simulated curve to become nearly superimposable on the experimental one. The EPR data indicated that the compound [Cu3(PhPyCNO)3(μ3-OH)(2,4,5-T)2] (1), where 2,4,5-T is 2,4,5-trichlorophenoxyacetate, has isosceles or lower magnetic symmetry (δ ≠ 0), that antisymmetric exchange is important (G ≠ 0), and that ΔE > hν. The structures of the complexes 1 and [Cu3(PhPyCNO)3(μ3-OH)(H2O)(ClO4)2] (2) were determined using single-crystal X-ray crystallography. Theoretical calculations based on density functional theory were performed using the full crystal structures of 1, 2, [Cu3(PhPyCNO)3(OH)(CH3OH)2(ClO4)2] (3), and [Cu3(PhPyCNO)3(μ3-OMe)(Cl)(ClO4)] (4). The geometries of the model compounds [Cu3(κ3N,N,O-HNCHCHNO)3(μ3-OH)(μ2-HCOO)(HCOO)] (5), [Cu3(κ3N,N,O-HNCHCHNO)3(μ2-HCOO)(HCOO)]+ (6), [Cu3(κ3N,N,O-HNCHCHNO)3(μ3-O)]+ (7), and [Cu3(κ3N,N,O-HNCHCHNO)3]3+ (8) were optimized at the same level of theory for both the doublet and quartet states, and vibrational analysis indicated that the resulting equilibrium geometries corresponded to minima on the potential energy surfaces. Both eg and t2g magnetic orbitals seem to contribute to the magnetic exchange coupling. The latter contribution, although less important, might be due to overlap of the t2g orbitals with the p-type orbitals of the central triply bridging oxide ligand, thereby affecting its displacement from the Cu3 plane and contributing to the antiferromagnetic coupling. The crucial role of the triply bridging oxide (μ3-O) ligand on the antiferromagnetic exchange coupling between the three Cu(II) magnetic centers is further evidenced by the excellent linear correlation of the coupling constant J with the distance of the μ3-O ligand from the centroid of the Cu3 triangle

Structurally Diverse Copper(II)−Carboxylato Complexes: Neutral and Ionic Mononuclear Structures and a Novel Binuclear Structure

The copper complexes with the commercial auxin herbicides MCPA, 2,4-D, and 2,4,5-T in the presence of a nitrogen donor heterocyclic ligand, phen or bipyam, were prepared and characterized. The available evidence supports a dimeric structure for the 2,4-D complex in the presence of bipyam while phen leads to monomeric forms. The EPR spectrum of Cu2(2,4-D)4(bipyam)2 at 4 K in the solid state exhibits an axial signal which corresponds to almost isolated S = 1/2 magnetic ions. Magnetic data for the dimer show a weak antiferromagnetic interaction between the two metal ions with J = −0.8 cm-1. The crystal structures of tetrakis[(2,4-dichlorophenoxy)acetato]bis(2,2‘-bipyridylamine)dicopper(II), 1, bis(1,10-phenanthroline)[(2,4,5-trichlorophenoxy)acetato]copper(II) chloride, 2, and aqua(1,10-phenanthroline)bis[((2-methyl-4-chlorophenoxyacetato]copper(II), 3, were determined and refined by least-squares methods using three-dimensional MoKα data. 1 crystallizes in space group P1̄, in a cell of dimensions a = 10.813(1) Å, b = 12.138(1) Å, c = 11.909(1) Å, α = 86.448(3)°, β = 80.127(3)°, and γ = 63.982(3)°, and V = 1383.7(2) Å3, with Z = 1. 2 crystallizes in space group I2/a, in a cell of dimensions a = 29.958(9) Å, b = 11.342(3) Å, c = 21.196(7) Å, β = 107.94(1)°, and V = 6852.2(4) Å3, with Z = 8. 3 crystallizes in space group P1̄, in a cell of dimensions a = 8.7419(8) Å, b = 12.512(1) Å, c = 14.598(1) Å, α = 110.737(1)°, β = 95.742(2)°, γ = 103.286(2)°, V = 1424.1(2) Å3, with Z = 2