FeII4L4 tetrahedron binds and aggregates DNA G-quadruplexes

Since the discovery of the G-quadruplex (G4) structure in telomeres in 1980s, studies have established the role it plays in various biological processes. Here we report binding between DNA G4 and a self-assembled tetrahedral metal-organic cage 1 and consequent formation of aggregates, whereby the cage protects the DNA G4 from cleavage by S1 nuclease. We monitor DNA–cage interaction using fluorescence spectroscopy, firstly by quenching of a fluorescent label appended to the 5′ end of G4. Secondly, we detect the decrease in fluorescence of the G4-selective dyes thioflavin-T and Zn-PPIX bound to various DNA G4 sequences following the addition of cage 1. Our results demonstrate that 1 interacts with a wide range of G4s. Moreover, gel electrophoresis, circular dichroism and dynamic light scattering measurements establish the binding of 1 to G4 and indicate the formation of aggregate structures. Finally, we find that DNA G4 contained in an aggregate of cage 1 is protected from cleavage by S1 nuclease.

We find Fe^II₄L₄ binds to G-quadruplex and forms aggregates. G-quadruplex in the aggregates is protected from digestion by S₁ nuclease.     

Thermoplastic processing of protein-based bioplastics: chemical engineering aspects of mixing,extrusion and hot molding

Proteins, as heteropolymers, offer a large range of possible interactions and chemical reactions. The thermoplastic behavior of proteins has been studied in order to produce bioplastics by thermal or thermomechanical processes such as mixing, extrusion or hot molding. The extrusion trials were performed by using a co-rotating twin-screw extruder, recording torque, temperature and die pressure. Batch mixing was done in a two blade counter-rotating mixer, with continuous recording of torque and product temperature. Proteins were alternatively extruded, mixed or hot molded under a large range of processing conditions. Protein aggregation during each process was estimated from the accumulation of SDS-insoluble protein fraction. Protein aggregation evidences a cross-linking reaction the activation energy of which was dependent on the thermoplastic process used. The increase in network density appears to be induced by the severity of the treatment: temperature and shear strongly affect the structural characteristics of the protein-based bioplastics.     

A Degradable Sustained-Release Drug Delivery System for Bleb-Forming Glaucoma Surgery

Fibrosis of the filtering bleb is one of the main causes of failure after bleb-forming glaucoma surgery. Intraoperative application of mitomycin C (MMC) is the current gold standard to reduce the fibrotic response. However, MMC is cytotoxic and one-time application is often insufficient. A sustained-release drug delivery system (DDS), loaded with MMC, may be less cytotoxic and equally or more effective. Two degradable (polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA)) MMC-loaded DDSs are developed. Release kinetics are first assessed in vitro followed by rabbit implants in conjunction with the PRESERFLO MicroShunt. As a control, the MicroShunt is implanted with adjunctive use of a MMC solution. Rabbits are euthanized at postoperative day (POD) 28 and 90. The PLGA and PCL DDSs release (on average) 99% and 75% of MMC, respectively. All groups show functioning blebs until POD 90. Rabbits implanted with a DDS show more inflammation with avascular thin-walled blebs when compared to the control. However, collagen is more loosely arranged. The PLGA DDS shows less inflammation, less foreign body response (FBR), and more complete degradation at POD 90 when compared to the PCL DDS. Further optimization with regard to dosage is required to reduce side effects to the conjunctiva.     

ChemInform Abstract: Tetrayttrium Difluoride Disilicate Orthosilicate,Y4F2[Si2O7][SiO4].

Colorless lath-shaped single crystals of the title compound are obtained from a melt of Y₂O₃, YF₃, and SiO₂ (2:5:3 molar ratio) using CsCl as a flux (evacuated silica tube, 973 K, 9 d, 10 K/h cooling rate).     

Highly Effective and Green Catalytic Approach Toward α,ω‐Dihydroxy‐Telechelic Poly(trimethylenecarbonate)

α,ω‐Dihydroxy‐telechelic poly(trimethylenecarbonate), HO‐PTMC‐OH, is synthesized from the controlled “immortal” ring‐opening polymerization (ROP) of trimethylene carbonate under mild conditions (bulk, 60 °C), using ZnEt₂ or, more efficiently, [(BDI)Zn(N(SiMe₃)₂)] (BDI = CH(CMeNC₆H₃‐2,6‐iPr₂)₂) as catalyst precursor, in the presence of a diol HO‐R‐OH (R = (CH₂)₂ or CH₂C₆H₄CH₂; 0.5–10 equiv. vs Zn) acting both as co‐initiator and chain transfer agent. Alternatively, HO‐PTMC‐OH is prepared upon hydrogenolysis of HO‐PTMC‐OCH₂Ph, initially prepared from the ROP of TMC using the [(BDI)Zn(N(SiMe₃)₂)]/PhCH₂OH system, under smooth operating conditions using Pd/charcoal. Well‐defined dihydroxy‐functionalized PTMCs of molar mass ranging from = 2 000 to 109 500 g · mol⁻¹ were thus quantitatively obtained and fully characterized by NMR, MALDI‐TOF‐MS and SEC analyses. The versatility of this “immortal” ROP allows the preparation of alike α,ω‐functional polyester such as linear HO‐poly(lactide)‐OH, as well as star polymers such as the glycerol‐based PTM‐OH₃.