Bis(acyl)phosphide - Ambidentate Ligands for the Synthesis of Group 14 and 15 Main Group Element Compounds.

The reactivity of the bis(acyl)phosphide ion [P(COR)2 ]- (BAP- , R=Ph, Mes) with silicon halides SiX4 (X=Cl, Br) and pnictogen chlorides ECl3 (E=As, Sb and Bi) was investigated. The reaction with SiX4 leads to the hexacoordinate silanes SiX2 (BAP)2 in which BAP- is coordinated in the chelating κ2 -O,O' mode, analogously to acac- . Unexpectedly, the coordination behaviour of BAP- differs from the one of acac- in the interpnictogen compounds E(BAP)3 (E=As, Sb) in which the formation of E-P bonds is favoured over κ2 -O,O' chelation via the oxygen centres. Finally, the reaction of BiCl3 with three equivalents of Na(BAP) leads to the formation of red, crystalline Bi2 (BAP)4 , an air stable dibismuthine, as product of a redox reaction.

ACTIVE-BAPO - A Versatile Transfer Agent for Photoactive Bis(acyl)phosphane Oxide Units.

A N-hydroxy succinimide (NHS) ester substituted bis(acyl)phosphane oxide (ACTIVE-BAPO) was prepared by phospha-Michael addition and used for an easy one-step BAPO ligation with substrates containing primary amino groups, such as amino acids, proteins, and poly(amidoamine) (PAMAM) dendrimers. Thereby, a range of new molecular and polymeric photoinitators was obtained. Real-time photo-rheology experiments demonstrated the outstanding efficiency of the PAMAM BAPOs as photoinitiators for free radical polymerization. Remarkably, it is found that PAMAM BAPOs also act as crosslinking agents to convert monofunctional methacrylate monomers into thermosetting networks without any further additives. Depending on the number of the attached BAPOs, thermosets with a different degree of crosslinking and swelling capability in water were obtained.

Organocatalyzed Phospha-Michael Addition: A Highly Efficient Synthesis of Customized Bis(acyl)phosphane Oxide Photoinitiators.

Addition of the P-H bond in bis(mesitoyl)phosphine, HP(COMes)2 (BAPH), to a wide variety of activated carbon-carbon double bonds as acceptors was investigated. While this phospha-Michael addition does not proceed in the absence of an additive or catalyst, excellent results were obtained with stoichiometric basic potassium or caesium salts. Simple amine bases can be employed in catalytic amounts, and tetramethylguanidine (TMG) in particular is an outstanding catalyst that allows the preparation of bis(acyl)phosphines, R-P(COMes)2 , under very mild conditions in excellent yields after only a short time. All phosphines RP(COMes)2 can subsequently be oxidized to the corresponding bis(acyl)phosphane oxides, RPO(COMes)2 , a substance class belonging to the most potent photoinitiators for radical polymerizations known to date. Thus, a simple and highly atom economic method has been found that allows the preparation of a broad range of photoinitiators adapted to their specific field of application even on a large scale.

1,3,4-Azadiphospholides as building blocks for scorpionate and bidentate ligands in multinuclear complexes.

Annulated oxy-substituted 1,3,4-azadiphospholides such as the anion in Na[1] are readily accessible phosphorus heterocycles made from the phosphaethynolate anion (OCP)- and 2-chloropyridines. The sodium salt Na[1] reacts with oxophilic element halides such as OPCl3, PhSiCl3, PhBCl2 and CpTiCl3 at room temperature to form exclusively the oxygen bound tris-substituted compounds E(1)3 (with E = OP, PhSi, PhB- or CpTi). Six equivalents of Na[1] with group four metal chlorides MCl4 (M = Ti, Zr, Hf) form cleanly the hexa-substituted dianions (Na2[M(1)6]) which are isolated in excellent yields. The titanium complexes are deeply coloured species due to ligand to metal charge transfer (LMCT) excitations. In all complexes, the phosphorus atoms of the azadiphosphole moieties are able to coordinate to a soft metal center as shown in their reactions with [Mo(CO)3Mes], yielding complexes in which the Mo(CO)3 binds in a fac manner. Functionalization of the oxy group with amino phosphanes allows isolation of tridentate ligands, which have been used as synthons for macrocyclic molybdenum carbonyl complexes.

In vitro Implementation of Photopolymerizable Hydrogels as a Potential Treatment of Intracranial Aneurysms.

Intracranial aneurysms are increasingly being treated with endovascular therapy, namely coil embolization. Despite being minimally invasive, partial occlusion and recurrence are more frequent compared to open surgical clipping. Therefore, an alternative treatment is needed, ideally combining minimal invasiveness and long-term efficiency. Herein, we propose such an alternative treatment based on an injectable, radiopaque and photopolymerizable polyethylene glycol dimethacrylate hydrogel. The rheological measurements demonstrated a viscosity of 4.86 ± 1.70 mPa.s, which was significantly lower than contrast agent currently used in endovascular treatment (p = 0.42), allowing the hydrogel to be injected through 430 µm inner diameter microcatheters. Photorheology revealed fast hydrogel solidification in 8 min due to the use of a new visible photoinitiator. The addition of an iodinated contrast agent in the precursor contributed to the visibility of the precursor injection under fluoroscopy. Using a customized light-conducting microcatheter and illumination module, the hydrogel was implanted in an in vitro silicone aneurysm model. Specifically, in situ fast and controllable injection and photopolymerization of the developed hydrogel is shown to be feasible in this work. Finally, the precursor and the polymerized hydrogel exhibit no toxicity for the endothelial cells. Photopolymerizable hydrogels are expected to be promising candidates for future intracranial aneurysm treatments.

Synthesis of γ-cyclodextrin substituted bis(acyl)phosphane oxide derivative (BAPO-γ-CyD) serving as multiple photoinitiator and crosslinking agent.

A new multi-photoactive γ-cyclodextrin substituted bis(acyl)phosphane oxide derivative (BAPO-γ-CyD) was successfully prepared via a convergent synthesis using a phospha-Michael-addition, as confirmed by 1H-, 13C-, 31P-NMR and IR spectroscopy and mass spectrometry. Kinetic studies carried out by photo-DSC and photo-rheology demonstrated its outstanding efficiency as a photoinitiator for free-radical polymerization. Remarkably, it is found that BAPO-γ-CyD also acts as a crosslinking agent to convert monofunctional methacrylate monomers into self-standing thermosetting networks with extensive swelling capability in water.

Pulsatile Flow-Induced Fatigue-Resistant Photopolymerizable Hydrogels for the Treatment of Intracranial Aneurysms.

An alternative intracranial aneurysm embolic agent is emerging in the form of hydrogels due to their ability to be injected in liquid phase and solidify in situ. Hydrogels have the ability to fill an aneurysm sac more completely compared to solid implants such as those used in coil embolization. Recently, the feasibility to implement photopolymerizable poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogels in vitro has been demonstrated for aneurysm application. Nonetheless, the physical and mechanical properties of such hydrogels require further characterization to evaluate their long-term integrity and stability to avoid implant compaction and aneurysm recurrence over time. To that end, molecular weight and polymer content of the hydrogels were tuned to match the elastic modulus and compliance of aneurysmal tissue while minimizing the swelling volume and pressure. The hydrogel precursor was injected and photopolymerized in an in vitro aneurysm model, designed by casting polydimethylsiloxane (PDMS) around 3D printed water-soluble sacrificial molds. The hydrogels were then exposed to a fatigue test under physiological pulsatile flow, inducing a combination of circumferential and shear stresses. The hydrogels withstood 5.5 million cycles and no significant weight loss of the implant was observed nor did the polymerized hydrogel protrude or migrate into the parent artery. Slight surface erosion defects of 2-10 µm in depth were observed after loading compared to 2 µm maximum for non-loaded hydrogels. These results show that our fine-tuned photopolymerized hydrogel is expected to withstand the physiological conditions of an in vivo implant study.