Behavior of the APSG electronic wavefunction near the electron‐electron coalescence point

The behavior of electronic wave functions within the antisymmetrized product of strongly orthogonal geminals (APSG) approximation at the point of the electron‐electron coalescence is examined. Its elucidation allows one to understand the origins of the previously reported satisfactory performance of APSG wavefunctions as reference states in the connected moments expansion method (CMX). It is shown that the failure to satisfy the electron‐electron cusp condition causes divergence of certain type of integrals that enter the CMX formulae, which in turn brings about significant deterioration of the quality of the resulting estimates for the ground‐state energy in finite basis sets.     

Activated protein C differentially regulates both viability and differentiation of osteoblasts mediated by bisphosphonates

Activated protein C (APC) is a cytoprotective anticoagulant that can promote cutaneous healing. We examined the effect of APC on viability and differentiation of the osteoblastic line, MG63, in the presence and absence of bisphosphonates (BPs). Osteoblasts were cultured and treated for 24 or 48 h with Alendronate (Aln), Zoledronate (Zol) or Pamidronate (Pam) at concentrations ranging from 10⁻⁴ to 10⁻⁶ ℳ. Cell differentiation was measured using type 1 collagen production, Alizarin red staining and alkaline phosphatase activity, whereas cell viability was assessed using MTT and crystal violet assays. All three BPs induced MG63 cell death in a dose- and time-dependent manner. Pam- and Zol-related cell death was prevented by APC treatment; however, cell death induced by Aln was accelerated by APC. APC induced MG63 cell differentiation that was enhanced by Aln, but inhibited by Pam or Zol. Endothelial protein C receptor (EPCR) was expressed by MG63 cells and mediated the protective effect of APC on Zol-induced viability. In summary, we have demonstrated that (1) APC favorably regulates MG63 viability and differentiation toward bone growth, (2) APC differentially regulates the effects of specific BPs and (3) at least part of the effects of APC is mediated through EPCR. These findings highlight the potential importance of the PC pathway in bone physiology and provide strong evidence that APC may influence bone cells and has potential to be a therapeutic drug for bone regeneration, depending on concurrent BP treatment.     

Further Understanding of the Reactivity Control of Bisphosphonates to a Metal Source for Fabricating Highly Ordered Mesoporous Films

Mesoporous metal organophosphonates having embedded organic functions are a promising platform to hybridize organics and non-siliceous inorganic frameworks in their molecular scale. However, the reactivity between a bisphosphonate and a metal source is dramatically different for their combination and then hampers to construct ordered mesoporous structures even when using amphiphilic organic molecules. By proposing an advanced method to adjust such reactivity, we recently succeeded in fabricating ordered mesoporous aluminum organophosphonate (AOP) films with chemically designable benzene units inside their hybrid frameworks. The reactivity of the organically bridged bisphosphonates has been controlled by utilizing dissimilar reactivities of acid–base pairs like P−OH and P−OEt groups to AlCl₃. Here, we further prove our reactivity-control concept through the introduction of organic groups, such as those having symmetric thiophene, asymmetric amide, and hydrophilic ether units. Liquid-state ³¹P NMR measurements further clarified the usefulness of the control of the −OH/ −OEt ratio in the same bisphosphonate molecules for obtaining highly ordered mesostructured AOP films.     

Base catalyzed unexpected rearrangement of isatin-derived N,N′-cyclic azomethine imines and Michael addition to hindered vinylidene bisphosphonates: Access to 3,3-disubstituted oxindole-fused pyrazolidin-3-one derivatives containing bisphosphonates

A new rearrangement of isatin-derived N,N′-cyclic azomethine imines to afford intermediate 3-hydroxy-1H-pyrazole -substituted oxindole was found, and then Michael addition of them to a vinyl bisphosphonate ester provided 3,3-disubstituted oxindole-fused pyrazolidone derivatives containing bisphosphonates in the presence of the readily available DMAP. This transformation is particularly attractive due to features such as unexpected rearrangement, mild conditions, atom economy, the ready availability of the starting materials.     

Gelatin Porous Scaffolds as Delivery Systems of Calcium Alendronate

The systemic administration of bisphosphonates (BPs) for the treatment of metabolic diseases characterized by abnormal bone loss suffers from several adverse side effects, which can be reduced by implementation of alternative modes of administration. In this work, glutaraldehyde cross‐linked gelatin scaffolds are proposed as delivery systems of calcium alendronate monohydrate (CaAL•H₂O). The 3D highly porous scaffolds display a relevant interconnected porosity (>94%), independently from CaAL•H₂O content (0, 3, and 6 wt%). At variance, pore size varies with composition. The relative increase of the number of smaller pores on increasing BP content is in agreement with the parallel significant increase of the compressive modulus and collapse strength. The scaffolds exhibit a sustained CaAL•H₂O release profile, and a significant amount of the drug is retained in the scaffolds even after 14 d. In vitro tests are carried out using cocultures of osteoblast (OB) and osteoclast (OC). The evaluation of differentiation markers is performed both on the supernatants of cell culture and by means of quantitative polymerase chain reaction. The results indicate that BP containing scaffolds support osteoblast proliferation and differentiation, whereas they inhibit osteoclast viability and activity, displaying a promising beneficial role on bone repair processes.

     

Geminal poly(silyl ester)s: Highly labile degradable polymers

Geminal silyl ester linkages were used for the backbone construction of linear polymers, which exhibit rapid cleavage in the presence of atmospheric water. A series of poly(gem-silyl ester)s with two ester groups flanking each silicon atom were synthesized, in order to probe the effects of different silyl-substituted side-chain groups upon the physical and chemical properties. The transsilylation condensation reaction of bis(trimethylsilyl) terephthalate with dichlorodiisopropylsilane, dichlorodicyclohexylsilane, dichloromethyl-n-octadecylsilane, and dichloromethyl-4-methylphenethylsilane gave the four poly(gem-silyl ester)s with two isopropyl, two cyclohexyl, one methyl plus one octadecyl, and one methyl plus one 4-methyl-phenethyl side-chain groups per silicon, respectively. The polymers were characterized by NMR (¹H, ¹³C, and ²⁹Si), infrared spectroscopy (IR), size-exclusion chromatography (SEC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Hydrolytic degradation studies of the polymers solvated in tetrahydrofuran and as bulk samples in the solid state were performed in the presence of atmospheric water as the nucleophilic cleavage agent, and the molecular weight loss was monitored by SEC. Poly(diisopropylsilyl terephthalate) (1a) and poly(dicyclohexylsilyl terephthalate) (1b) were found to be more stable towards nucleophilic degradation in comparison to poly(methyl-n-octadecylsilyl terephthalate) (1c) and poly(methyl-4-methylphenethylsilyl terephthalate) (1d), due to the presence of sterically bulky isopropyl or cyclohexyl groups attached to the silicon atoms. All of the polymers degraded into small molecules upon hydrolysis, with the exception that the degradation products of 1c and 1d self-condensed in the solid state to form the respective polysiloxanes. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3606–3613, 1999     

重新唤起人们兴趣的二氟氨基及其化合物

二氟氨基是提高含能化合物能量密度的最为理想的基团之一。在经过多年的沉寂之后, 近来二氟氨基及其化合物的研究又重新活跃起来。在积极寻求机械感度低、热稳定性好的二氟氨基化合物方面已获得重大进展。目前该领域的研究工作主要集中在二氟氨基取代环氧丁烷聚合物合成, 新戊基二氟氨基硝酸酯增塑剂制备, 以及环N₂硝胺基偕二氟氨基氧化剂的分子设计与合成上。     

One-pot two-step synthesis of fused thiazinofuranone linked geminal bis 1,2,3-triazole hybrids and their in vitro cytotoxic screening

In this study, a series of novel geminal bis 1,2,3-triazoles linked to 2H-furo[2,3-d][1,3]thiazine-2,4,5(1H,6H)-trione ( 3a-3m ) were prepared in one pot starting from 5-Acetyl-4-Hydroxy-1,3-thiazine-2,6-dione ( 1 ) to 6,6-diazido-2H-furo[2,3-d][1,3]thiazine-2,4,5(1H,6H)-trione ( 2 ) followed by Cu(I)-catalyzed azide-alkyne cycloaddition. The synthesized compounds were further explored for in vitro cytotoxic activity against PC3, A549, MCF-7, and HeLa cell lines and results revealed that the five compounds 3c , 3d , 3g , 3l , and 3m have displayed comparable in vitro cytotoxic activity with the standard drug Etoposide.     

Selective C−C Coupling of Vinyl Epoxides with Diborylmethide Lithium Salts

Vinyl epoxides and styrene oxide can react with diborylmethide lithium salts through an exclusive S_N2 borylmethylation/ring opening in a regio- and diastereoselective way, depending on the nature of the substrate. The ring-opening protocol provides homoallylboronates that can be transformed into challenging diastereomeric bishomoallylic alicyclic 1,3-diols. Unprecedented 3-borylated 1,2-oxaborolan-2-ol products were prepared by borylmethylation/ring opening of 2-methyl-2-vinyloxirane followed by intramolecular cyclization.