H-DL-Phe(4-Me)-OH

Objective: Residual scarring after cleft lip repair surgery remains a challenge for both surgeons and patients and novel therapeutics are critically needed. The objective of this preclinical experimental study was to evaluate the impact of the methyl-ester of pro-resolving lipid mediator lipoxin A4 (LXA4-ME) on scarring in a novel rabbit model of cleft lip repair. Methods: A defect of the lip was surgically created and repaired in eight six-week old New Zealand white rabbits to simulate human cleft lip scars. Rabbits were randomly assigned to topical application of PBS (control) or 1 ug of LXA4-ME (treatment). 42 days post surgery all animals were euthanized. Photographs of the cleft lip area defect and histologic specimens were evaluated. Multiple scar assessment scales were used to compare scarring. Results: Animals treated with LXA4-ME exhibited lower Visual Scar Assessment scores compared to animals treated with PBS. Treatment with LXA4-ME resulted in a significant reduction of inflammatory cell infiltrate and density of collagen fibers. Control animals showed reduced 2D directional variance (orientation) of collagen fibers compared to animals treated with LXA4-ME demonstrating thicker and more parallel collagen fibers, consistent with scar tissue. Conclusions: These data suggest that LXA4-ME limits scarring after cleft lip repair and improves wound healing outcomes in rabbits favoring the resolution of inflammation. Further studies are needed to explore the mechanisms that underlie the positive therapeutic impact of LXA4-ME on scarring to set the stage for future human clinical trials of LXA4-ME for scar prevention or treatment after cleft lip repair.

Cyano-bridged mixed-valence {Fe6} hexanuclear complexes {[Tp4-MeFeII(CN)3]2[FeIII(Tpa)]2[FeIII(OR)(Tpa)]2}·6ClO4·S (Tp4-Me = tri(4-methyl-pyrazol-1-yl)borate, Tpa = tris(2-pyridylmethyl)amine; R = -CH3, S = 8MeOH 1, R = -C2H5, S = 6EtOH 2) have been obtained by building the units of [Tp4-MeFe(CN)3]- and [Fe(Tpa)]2+ in methanol and ethanol, respectively. Complex 1 exhibited single-crystal-to-single-crystal (SCSC) transformation to give {[Tp4-MeFeII(CN)3]2[FeIII(Tpa)]2[FeIII(OH)(Tpa)]2}·6ClO4·8H2O (3) in water. Detailed analysis of the coordination environment of the FeIII centers on the square lattice and magnetic susceptibility measurements of all the complexes confirmed their Fe3+ spin-crossover (SCO) properties (T1/2 = 178 K, 1; 185 K, 2; 208 K, 3).

A polymer [Pd(CH2SO2C6H4Me)2]n is obtained by thermolysis of cis-[Pd(CH2SO2C6H4Me)2(NCMe)2] to release the MeCN ligands. The corresponding coordination sites are then occupied by weak Pd-O bonds, easier to break than the previous Pd-N bonds. This allows us to produce from the polymer cis complexes containing ligands weaker than NCMe, such as acetone or water. The complexes cis-[Pd(CH2SO2C6H4Me)2{OC(CD3)2}2], cis-[Pd(CH2SO2C6H4Me)2(OH2)2], and cis-[Pd(CH2SO2C6H4Me)2(OH2){OC(CD3)2}], and cyclic dimers [Pd(CH2SO2C6H4Me)2(OH2)]2 with bridging methylsulphone groups are formed. The Pd : PPh3 : OH2 1 : 1 : 1 reaction of the polymer produces cis-[Pd(CH2SO2C6H4Me)2(OH2)(PPh3)], which isomerizes to trans-[Pd(CH2SO2C6H4Me)2(OH2)(PPh3)], with water O-coordinated to Pd and making hydrogen bonds to the two SO2 groups as seen in its X-ray structure. A similar role is played by RNH2 groups in the structures of trans-[Pd(CH2SO2C6H4Me)2(NH3)(PPh3)] and the dimer μ-(N2H4)(trans-[Pd(CH2SO2C6H4Me)2(PPh3)])2. In addition to these interesting intramolecular hydrogen bonding properties provided by the SO2 groups, the structural and 1H NMR data available suggest that the CH2SO2C6H4Me group is an interesting kind of strong alkyl σ donor, with high trans influence, and forms very stable Pd complexes extraordinarily resistant to reductive elimination and to hydrolysis by water at room temperature.