Amyloid ß chaperone - lipocalin-type prostaglandin D synthase acts as a peroxidase in the presence of heme.

The extracellular transporter, lipocalin-type prostaglandin D synthase (L-PGDS) binds to heme and heme metabolites with high affinity. It has been reported that L-PGDS protects neuronal cells against apoptosis induced by exposure to hydrogen peroxide. Our study demonstrates that when human WT L-PGDS is in complex with heme, it exhibits a strong peroxidase activity thus behaving as a pseudo-peroxidase. Electron paramagnetic resonance studies confirm that heme in the L-PGDS-heme complex is hexacoordinated with high-spin Fe(III). NMR titration of heme in L-PGDS points to hydrophobic interaction between heme and several residues within the ß-barrel cavity of L-PGDS. In addition to the transporter function, L-PGDS is a key amyloid ß chaperone in human cerebrospinal fluid. The presence of high levels of bilirubin and its derivatives, implicated in Alzheimer's disease, by binding to L-PGDS may reduce its chaperone activity. Nevertheless, our ThT binding assay establishes that heme and heme metabolites do not significantly alter the neuroprotective chaperone function of L-PGDS. Guided by NMR data we reconstructed the heme L-PGDS complex using extensive molecular dynamics simulations providing a platform for mechanistic interpretation of the catalytic and transporting functions and their modulation by secondary ligands like Aß peptides and heme metabolites.

A Monoaryllead Trichloride That Resists Reductive Elimination.

Transmetallation of Pb(OAc)4 with R2 Hg (1), followed by treatment with HCl in Et2 O, provided RPbCl3 (2), the first kinetically stabilized monoorganolead trihalide that resists reductive elimination under ambient conditions. The kinetic stabilisation relies on an intramolecularly coordinating O-donor substituent (R=6-Ph2 P(O)-Ace-5-). The gram-scale preparation of 2 was key for the synthesis of unsymmetrically substituted diaryllead dichlorides RR'PbCl2 (3 a, R'=Ph; 3 b, R'=4-MeOC6 H4 ; 3 c, R'=4-Me2 NC6 H4 ).

Role of Dispersion in Metallophilic Hg···M Interactions (M = Cu, Ag, Au) within Coinage Metal Complexes of Bis(6-diphenylphosphinoacenaphth-5-yl)mercury.

The previously reported bis(6-diphenylphosphinoacenaphth-5-yl)mercury (1) was used as ligand for the preparation of the copper(I) complexes, 1·CuCl and [1·Cu(NCMe)]BF4, which were characterized by multinuclear NMR spectroscopy and X-ray crystallography. DFT calculations employing topological analysis of the electron and electron pair densities within the AIM and ELI-D space-partitioning schemes revealed significant metallophilic Hg···Cu interactions. Evaluation of noncovalent bonding aspects according to the noncovalent interaction (NCI) index was applied not only for the Cu complexes 1·CuCl and [1·Cu(NCMe)]BF4 but also for the previously reported Ag and Au complexes, namely, [1·MCl] (M = Ag, Au) and [1·M(NCMe)n]+ (M = Ag, n = 2; M = Au, n = 0), and facilitated the assignment of attractive dispersive Hg···M interactions with the Hg···Cu contacts being comparable to the Hg···Ag but weaker than the Hg···Au interactions. The localization of the attractive noncovalent bonding regions increases in the order Cu < Ag < Au.

Increasing the Brønsted acidity of Ph2PO2H by the Lewis acid B(C6F5)3. Formation of an eight-membered boraphosphinate ring [Ph2POB(C6F5)2O]2.

Autoprotolysis of the metastable acid (C6F5)3BOPPh2OH, prepared in situ by the reaction of the rather weak Brønsted acid Ph2PO2H with the strong Lewis acid B(C6F5)3, gave rise to the formation of the eight-membered ring [Ph2POB(C6F5)2O]2 and C6F5H. The conjugate base was isolated as stable sodium crown ether salt [Na(15-crown-5)][Ph2PO2B(C6F5)3].

Lewis-acid induced disaggregation of dimeric arylantimony oxides.

The previously known dimeric arylantimony oxides (Ph3SbO)2 and [2,6-(Me2NCH2)2C6H3SbO]2 were disaggregated by the Lewis acid B(C6F5)3 giving rise to the formation of the Lewis pair complexes Ph3SbOB(C6F5)3 and 2,6-(Me2NCH2)2C6H3SbOB(C6F5)3 having short bipolar single Sb-O bonds.