Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

We present the comparative preparation of [Co 7 ( μ 3 -OH) 6 (L) 6 ](ClO 4 ) 2 3 12H 2 O (1), [Co 7 ( μ 3 -CH 3 O) 6 -(L) 6 ](ClO 4 ) 2 (2), and [Co 7 ( μ 3 -N 3 ) 6 (L) 6 ](ClO 4 ) 2 (3), where HL is 2-methoxy-6-[(methylimino)methyl]phenol, using traditional (e.g., 120 °C, 120 h, 23% yield for 1) and microwave-assisted (e.g., 120 °C, 10 min, 46% yield for 1) solvothermal synthesis. The structures contain Co 7 brucite disk [Co 7 ( μ 3 -X) 6 ( μ 2 -O) 6 ] 2þ , where the ligands are arranged in two open hemispheres and the flat inner surface is functionalized when X is OH -, CH 3 O -, and N 3 -. The symmetry of the core decreases in the order 1 > 2 > 3, according to the shape, size, and rigidity of the inner bridges (X). These units are stacked into a chain, and for 1, the water molecules provide a hydrogen-bonded network through the hydroxyl groups. Interestingly, electrospray ionization mass spectrometry (ESI-MS) indicates that the heptacobalt(II) clusters of 1-3 exist in solution and the their compositions in solution are similar to those in the solid. However, the inner ligands μ 3 -CH 3 Oand N 3 are replaced partially with μ 3 -OH -, indicating that μ 3 -OHhas a greater affinity than μ 3 -CH 3 Oor N 3 for Co II , and the parental core of [Co 7 (OH) 6 (L) 6 ] 2þ is the most stable of the three compounds in solution. The presence of edge-sharing octahedra through μ 3 -O or μ 3 -N provides ferromagnetic coupling between nearest neighbors in all cases. Interestingly, for μ 3 -N, it appears to be stronger than μ 3 -O which resulted in single-molecule magnet (SMM) behavior at a higher temperature of 3 K, while they are below the limit of the SQUID magnetometers (2 K) in the case of 1 and 2.

Aerobic photo-oxidation of sulfide into sulfoxide in water is of great interest in green chemistry. In this study, three highly stable Ir­(III)–Zr­(IV) metal–organic frameworks (Ir–Zr MOFs), namely Zr6–Irbpy (bpy is 2,2′-bipyridine), Zr6–IrbpyOMe (bpyOMe is 4,4′-dimethoxy-2,2′-bipyridine), and Zr6–Irphen (phen is 1,10-phenanthroline), are constructed by using [Ir­(pqc)2(L)2]Cl complexes (where pqc is 2-phenylquinoline-4-carboxylic acid and L is an ancillary ligand bpy, bpyOMe, or phen) as linkers and Zr6 cluster as nodes. The constructed Ir–Zr MOFs present high catalytic activity on aerobic photo-oxidation of sulfide into sulfoxide under visible light irradiation in water at room temperature. Moreover, the reaction is high chemoselectivity and functional group tolerance. The catalyst can be readily recycled and reused at least 10 times without loss of catalytic activity. Mechanism studies demonstrate that superoxide radical is the reactive oxygen species in the sulfoxidation, which is generated by electron transfer from the excited triplet photosensitizer 3[Ir–Zr-MOF]* to O2. The high activity of photocatalytic sulfoxidation in water may be attributed to the stabilization of the persulfoxide intermediate by hydrogen bond formation with water solvent, which accelerates the conversion of persulfoxide into sulfoxide and prevents further oxidation of sulfoxide into sulfone. This work provides a new strategy for the green synthesis of sulfoxides under ambient conditions.

Diastereoselective synthesis of bis-cyclometalated Ir(III) stereoisomers Δ/Λ-[Ir(C ∧ N) 2 (D-pro)] and Δ/Λ-[Ir-(C ∧ N) 2 (L-pro)] (where C ∧ N is 2-phenylpyridine (Hppy), (4,6difluorophenyl)pyridine (Hdfppy), and 2-phenylquinoline (Hpq) and pro is proline) with dual stereogenic centers at the metal and auxiliary ligand has been developed. The diastereomers Λ-L and Λ-D, and Δ-L and Δ-D exhibit distinguishable photophysical properties in both solution and the solid state. The thermodynamically stable diastereomers Λ-[Ir(ppy) 2 (L-pro)], Λ-[Ir(dfppy) 2 (Lpro)], and Λ-[Ir(pq) 2 (L-pro)] emit a green emission at 524 nm (Φ = 3.5% and τ = 35 ns), a blue-green emission at 480 nm (Φ = 4.5% and τ = 59 ns), and a red emission at 588 nm (Φ = 6.5% and τ = 200 ns) in DCM solution, respectively, which are blue-shifted accompanied by a large quantum yield and long lifetime relative to the corresponding unstable diastereomers Δ-[Ir(ppy) 2 (L-pro)] at 537 nm (Φ = 2.3% and τ = 29 ns), Δ-[Ir(dfppy) 2 (L-pro)] at 489 nm (Φ = 2.8% and τ = 43 ns), and Δ-[Ir(pq) 2 (L-pro)] at 591 nm (Φ = 5.4% and τ = 192 ns). Similar cases were also observed in crystals, but the signals were significantly red-shifted with respect to those in solution. Single-crystal structural analyses show that the Δ-L and Λ-D diastereomers exhibit larger interligand repulsion and loose molecular packing with respect to the Δ-D and Λ-L diastereomers, resulting in energy and photophysical property differences. In addition, the isomers with Δ and Λ configurations at the metal center exhibit positive and negative circularly polarized luminescence (CPL) signals, respectively, indicating that the effects of the chiral carbon atoms in pro ligands on CPL signals are negligible.