Pharmacokinetics and Changes in Lipid Mediator Profiling after Consumption of Specialized Pro-Resolving Lipid-Mediator-Enriched Marine Oil in Healthy Subjects.

Omega-3 polyunsaturated fatty acids (PUFAs) play a vital role in human health, well-being, and the management of inflammatory diseases. Insufficient intake of omega-3 is linked to disease development. Specialized pro-resolving mediators (SPMs) are derived from omega-3 PUFAs and expedite the resolution of inflammation. They fall into categories known as resolvins, maresins, protectins, and lipoxins. The actions of SPMs in the resolution of inflammation involve restricting neutrophil infiltration, facilitating the removal of apoptotic cells and cellular debris, promoting efferocytosis and phagocytosis, counteracting the production of pro-inflammatory molecules like chemokines and cytokines, and encouraging a pro-resolving macrophage phenotype. This is an experimental pilot study in which ten healthy subjects were enrolled and received a single dose of 6 g of an oral SPM-enriched marine oil emulsion. Peripheral blood was collected at baseline, 3, 6, 9, 12, and 24 h post-administration. Temporal increases in plasma and serum SPM levels were found by using LC-MS/MS lipid profiling. Additionally, we characterized the temporal increases in omega-3 levels and established fundamental pharmacokinetics in both aforementioned matrices. These findings provide substantial evidence of the time-dependent elevation of SPMs, reinforcing the notion that oral supplementation with SPM-enriched products represents a valuable source of essential bioactive SPMs.

New Pt→M (M = Ag or Tl) complexes based on anionic cyclometalated Pt(ii) complexes.

Anionic cyclometalated complexes (NBu4)[Pt(CNC)X] (X = Cl (1), CN (2), or S-2py (pyridine-2-thiolate) (3); -CNC- = 2,6-di(phen-2-ide)-pyridine) have been used as precursors in the synthesis of heteropolynuclear Pt-Ag or Pt-Tl complexes containing donor-acceptor metal-metal bonds. Their reaction with AgClO4 or [Ag(OClO3)(PPh3)] produces complexes in which the nuclearity and structure seem to be determined by the ability of the ligand X to form bridges between the metals. Thus, the characteristic linear bridging of the cyano ligand leads to the formation of an octanuclear [{Pt(CNC)(µ-CN)}4Ag4] (4) or tetranuclear [{Pt(CNC)(µ-CN)}2{Ag(PPh3)}2] (6) complex, with CN bridges between different "Pt-Ag" units. However, the S-2py ligand can act as a bridge between Pt and Ag of the same "Pt-Ag" unit, giving rise to the complex [{Pt(CNC)(S-2py)}2Ag2]·CH2Cl2 (5). On the other hand, the reaction of 1-3 with TlPF6 yields the complexes [PtTl(CNC)Cl] (7), [PtTl(CNC)(CN)] (8), and (NBu4)[{Pt(CNC)(S-2py)}2Tl] (9), while with [Tl(S-2py)], [PtTl(CNC)(S-2py)] (10) is obtained. The structures of all these Pt-Tl complexes show great variation, with several geometric arrangements which sometime co-exist in the same crystal structure: discrete Pt-Tl, Pt-Tl-Pt and Pt-Tl-Pt-Tl units, as well as infinite Pt-Tl-Pt-Tl chains. This variability could be due to the lability of the Pt-Tl bonds and the ability of the thallium center to establish secondary interactions with donor atoms or aromatic π electron density from neighboring moieties.

Pt-M Complexes (M=Ag, Au) as Models for Intermediates in Transmetalation Processes.

Heteropolynuclear complexes [(CNC)(PPh3 )PtM(PPh3 )]ClO4 [M=Au (1), Ag (2)] and [{Pt(CNC)(PPh3 )}2 M]ClO4 [M=Ag (3), Au (4); CNC=2,6-diphenylpyridinate] were prepared and studied by X-ray crystallography, spectroscopic techniques, and DFT calculations. The X-ray crystal structures of 1, 3, and 4 confirmed the existence of Pt-M bonds and M⋅⋅⋅Cipso interactions involving one of the phenyl fragments of CNC. Their NMR spectra showed the persistence of the Pt-M interactions in solution and also revealed an intramolecular metronome-like dynamic process consisting of back-and-forth motion of the acidic M fragments along the C-Pt-C axis. DFT calculations on these complexes identified two main orbital interactions between the [PtCNC] and [M]+ fragments, namely, donation from the former to a vacant orbital of the latter and much weaker backdonation from the acidic M to the Pt fragment. Overall, the strength of the [Pt]⋅⋅⋅M interactions is higher for the gold compounds than for their silver counterparts. The interaction between the acidic center (silver or gold) and the carbon atom of one of the phenylene rings in these heteropolymetallic complexes can be envisaged as the first step in a process of interchange of aryl ligands. However, the ligand exchange cannot progress further due to the polydentate nature of the CNC ligand, and therefore these structures can be considered as frozen snapshots of a transmetalation reaction that has been arrested at different stages of the process.

Correction: Preparation of Pt-Tl clusters showing new geometries. X-ray, NMR and luminescence studies.

Correction for 'Preparation of Pt-Tl clusters showing new geometries. X-ray, NMR and luminescence studies by Úrsula Belío et al., Dalton Trans., 2014, 43, 10828-10843.

Unusual Metal-Metal Bonding in a Dinuclear Pt-Au Complex: Snapshot of a Transmetalation Process.

The dinuclear Pt-Au complex [(CNC)(PPh3 )Pt Au(PPh3 )](ClO4 ) (2) (CNC=2,6-diphenylpyridinate) was prepared. Its crystal structure shows a rare metal-metal bonding situation, with very short Pt-Au and Au-Cipso (CNC) distances and dissimilar Pt-Cipso (CNC) bonds. Multinuclear NMR spectra of 2 show the persistence of the Pt-Au bond in solution and the occurrence of unusual fluxional behavior involving the [Pt(II) ] and [Au(I) ] metal fragments. The [Pt(II) ]⋅⋅⋅ [Au(I) ] interaction has been thoroughly studied by means of DFT calculations. The observed bonding situation in 2 can be regarded as a model for an intermediate in a transmetalation process.

Preparation of Pt-Tl clusters showing new geometries. X-ray, NMR and luminescence studies.

Square planar complexes [Pt(CNC)L] (CNC = C,N,C-2,6-NC5H3(C6H4-2)2; L = tht (tetrahydrothiophene, SC4H8, 1), L = CN(t)Bu (2)) react with TlPF6 in different Pt/Tl molar ratios (3/1 in the case of 1 and 1/1 in the case of 2) yielding the complexes [{Pt(CNC)(tht)}3Tl](PF6) (3) and [Pt(CNC)(CN(t)Bu)Tl](PF6) (4), respectively. The structures of 3 and 4 (X-ray) show the presence of Pt→Tl dative bonds unsupported by any bridging ligands. In complex 3, the only Tl centre is simultaneously bonded to three Pt atoms forming a perfect equilateral triangle with Pt-Tl distances of 2.9088(5) Å, remarkably short. Complex 4 is formed by three "Pt(CNC)(CN(t)Bu)Tl" units, disposed in a triangular fashion, linked together through η(6)-Tl-arene interactions, and showing Pt-Tl bonds with distances of ca. 3.04 Å. The study of these crystal structures would seem to indicate that the difference between the Pt/Tl ratios found in the complexes 3 and 4 is due to the steric requirements of the L ligand bonded to Pt. NMR studies both in solution and in the solid state show that the Pt-Tl bond persists in solutions of 3 and 4. The UV-vis spectra of 3 and 4 in solution display the same profiles as those of 1 and 2, which may suggest a partial dissociation of the Pt-Tl bond in solution. However, by DFT calculations it was proved that in this case the formation of the Pt-Tl dative bond does not produce the expected blue-shift in the UV-vis absorptions. The emissive behaviour of 1-4 in the solid state and in frozen solutions is also studied and included in this work.

Synthesis, characterization, and computational study of complexes containing Pt···H hydrogen bonding interactions.

Complexes [Pt(C6F5)(bzq)L] (bzq = 7,8-benzoquinolinate; L = 8-hydroxyquinoline, hqH (1); 2-methyl-8-hydroxyquinoline, hqH' (2)) have been prepared by replacing the labile acetone ligand in the starting material [Pt(C6F5)(bzq)(Me2CO)]. The (1)H NMR spectra of 1 and 2 show that the signals attributable to the hydroxyl proton of the hqH or hqH' ligands are displaced downfield 2.64 ppm for 1 and 2.74 ppm for 2 with respect to the respective free ligands. Moreover, in both complexes the signals present platinum satellites with J(Pt,H) coupling constant of 67.0 Hz for 1 and 80.6 Hz for 2. All these features are indicative of the existence of Pt···H-O hydrogen bonds in solution for these complexes. The structures of complexes 1 and 2 have been established by an X-ray diffraction study and allow us to confirm the existence of these interactions in the solid state too. Thus, in both cases the hydroxyl hydrogen atom is pointing toward the metal center, and the measured geometric parameters involving this hydrogen are Pt-H = 2.09(4) Å, O-H = 0.94(4) Å, Pt-H-O 162(4)°, for 1, and Pt-H = 2.10(4) Å, O-H = 0.91(4) Å, Pt-H-O 162(4)°, for 2, all of which are fully compatible with a hydrogen bond system. Complexes 1 and 2 and the analogues [Pt(C6F5)3(hqH)](-) (A) and [Pt(C6F5)3(hqH')](-) (B), prepared some time ago in our laboratory and also showing Pt···H-O hydrogen bonds, have been the object of theoretical calculations to obtain better insight into the Pt···H interactions. Their density functional theory (DFT) calculated structures show excellent agreement with the X-ray determined ones (1, 2, and B). Topological analyses of the electron density function (ρ(r)) have been performed on the four complexes according to Bader's Atoms In Molecules theory. These analyses reveal a bond path that relates the platinum atom and the hydroxyl hydrogen atom, as well as the corresponding bond critical points. The values of the Laplacian ∇(2)ρ(r) and local energy density H(r) indicate that these are closed shell, electrostatic interactions, but with partial covalence. The deprotonation of the OH fragment in 1 and 2 with BuLi leads to the formation of the unexpected trinuclear complexes (NBu4)[Li{Pt(C6F5)(bzq)(L)}2] (L = hq (3), hq' (4)). The X-ray structures of these have shown a change in the coordination of the deprotonated hq and hq', which are now bonded to the Pt atoms through their O atoms, and which are bridging the Pt and Li metal atoms.

Synthesis and characterization of a "Pt3Tl" cluster containing an unprecedented trigonal environment for thallium(I).

The tetranuclear [{Pt(CNC)(tht)}3Tl](PF6) (tht = tetrahydrothiophene; SC4H8; CNC = C,N,C-2,6-NC5H3(C6H4-2)2; 2) cluster has been prepared by the reaction of [Pt(CNC)(tht)] (1) and TlPF6 (molar ratio 3:1) and structurally characterized. The Tl(I) atom is bonded to three Pt(II) centers bearing a perfect trigonal coordination. The Pt(II)-Tl(I) bonds are unsupported by any bridging ligand and are the shortest of this kind reported so far [2.9086(5) Å]. These intermetallic bonds persist in a CD2Cl2 solution, as shown by the (195)Pt{(1)H} NMR spectrum of 2 at 193 K, in which a Pt-Tl coupling of 8.9 kHz is observed.