Magnetic Properties of π-Conjugated Hybrid Phenoxyl-Nitroxide Radicals with Extended π-Spin Delocalization.

A series of stable and genuinely organic open-shell systems, π-conjugated phenoxyl-nitroxide free radicals (hybrid phenoxyl-nitroxide radicals), have been synthesized and their magnetic properties in the crystalline state investigated, revealing their usefulness as new building blocks for molecular magnetic materials. The salient electronic structure of the hybrid phenoxyl-nitroxide radicals is extended π-spin delocalization from the nitroxide moiety, mediating the localization effect intrinsic to nitroxide radicals. Five representative hybrid radicals containing an aliphatic, aromatic, and heteroaromatic substituent in the side part of the compact hybrid radical centers were synthesized, and their molecular/crystal structures in the crystalline state were determined by X-ray diffraction analyses. CW X-band ESR, 1H-ENDOR spectroscopy, and DFT calculations for the hybrid radicals confirmed that an unpaired spin delocalizes over the whole molecular frame including the nonconjugated fragments, suggesting the possibility of tuning their electronic properties through substituent effects in the crystalline state. Significant influence of the phenoxyl moiety on the electronic structure was analyzed in terms of the g-tensor calculations. The SQUID magnetization measurements revealed that the nitroxides bearing alkyl or aromatic substituents behave as 3D Curie-Weiss paramagnets with weak antiferromagnetic (AFM) (Θ = -1 to -2.6 K) or ferromagnetic (FM) (Θ = +0.33 K) spin-spin exchange interactions. On the other hand, heteroaromatically substituted hybrid phenoxyl-nitroxide showed significant AFM interactions with J/kB = -25.6 K. The analysis of the bulk magnetic properties based on the crystallographic data and DFT calculations revealed competition between the intermolecular AFM and FM interactions which originate from the C-O(phenoxyl)···Me(nitroxide) or (N)O-C(arom) infinite 1D head-to-tail chains and the C(arom)-C(arom) head-over-tail dimers forming 3D networks in their crystal lattices.

A visible-light-induced cascade reaction of etherification/C-C cyclization: efficient synthesis of dibenzo[b,d]oxepin-7(6H)-ones.

A visible-light-induced palladium-catalyzed cascade reaction was developed by etherification/C-C coupling cyclization of α-bromoacetophenones with phenols. A series of dibenzo[b,d]oxepin-7(6H)-one derivatives were efficiently synthesized by using this method in good yields. Furthermore, this method was applied to the synthesis of protosappanin A. The protocol has advantages such as simple reaction conditions, wide range of substrates and high reaction efficiency.

P58(IPK) inhibition of endoplasmic reticulum stress in human retinal capillary endothelial cells in vitro.

PURPOSE: The goal of this research was to determine if P58(IPK), a member of the Hsp40 family that inhibits eukaryotic initiation factor 2alpha (eIF2alpha), inhibits endoplasmic reticulum (ER) stress and leads to downregulated expression of vascular endothelial growth factor (VEGF) and decreased apoptosis in human retinal capillary endothelial cells (HRCECs). METHODS: Recombinant vectors were constructed using P58 in adeno-associated virus type 2 (rAAV2-P58 (IPK)) and P58 RNA in the plasmid pGIPZ (pGIPZ-P58(IPK)). The four experimental groups were: (1) non-transfected/non ER stressed control; (2) non-transfected/ER stressed; (3) rAAV2-P58(IPK)-transfected/ER stressed; and (4) pGIPZ- P58(IPK) RNAi transfected/ER stressed. ER stress was induced by treating cells with tunicamycin. Expression of P58(IPK) was determined in transfected cells. Expressions of the following factors were assessed: vascular endothelial growth factor (VEGF), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), and glucose-regulated protein 78 (GRP78). Apoptosis levels were also determined. RESULTS: Significantly increased expression of P58(IPK) was detected in cells transfected with rAAV2-P58(IPK) (0.63+/-0.02) as compared to those transfected with pGIPZ-P58(IPK) RNAi (0.23+/-0.01). P58(IPK) expression was not different between the control transfected cells (rAAV2-GFP and pGIPZ-GFP). Following ER stress, expression levels of ATF-4, GRP78, CHOP, and VEGF in cells overexpressing P58(IPK) were not different from those in unstressed control cells. This inhibitory effect of P58(IPK) on the expression of ER stress-related factors was suppressed in cells transfected with pGIPZ-P58(IPK) RNAi. Apoptosis was significantly increased in cells transfected with pGIPZ-P58(IPK) RNAi but not with rAAV2-P58(IPK). CONCLUSIONS: The study demonstrates that P58(IPK) inhibits ER stress and plays an important role in maintaining balance and stability of the ER in HRCECs.