Surface functionalization of a poly(butylene terephthalate) (PBT) melt-blown filtration membrane by wet chemistry and photo-grafting.

The surface functionalization of PBT melt-blown membrane, making up a whole filter of blood components, was achieved via two methods. Hydroxyl chain-end activation by tosylation (method A), followed by coupling of F- and (3)H-tagged molecules (probes), led to 1% of surface derivatization (XPS) and 290 pmol/cm(2) of lysine fixation (LSC). Deposition of O-succinimidyl 4-(p-azido-phenyl)butanoate ("molecular clip") and 2 h irradiation at 254 nm led to the implanting of activated ester functions, randomly on the polymer surface (method B). Further coupling of F- and (3)H-probes by wet chemistry gave highly functionalized surface (4% by XPS and 1000 pmol/cm(2) by LSC). However, control experiments showed that about 80% of the surface derivatization resulted from the UV treatment alone. Thus, the effect of UV irradiation on PBT membrane was systematically studied and analyzed by XPS, contact angle measurements, GPC and surface reactivity assays. The optimized conditions of "molecular clip" photo-grafting (negligible polymer photo-oxidation/photo-degradation) led to the covalent fixation of 45 pmol/cm(2) of (3)H-probe. Throughout our study, the behaviour of PBT melt-blown membrane was compared to PBT film and PET track-etched membrane similarly treated. Lastly, the method B was applied to couple GRGDS peptide on the PBT membrane; this material showed improved properties of leukocyte depletion in buffy coat filtration experiments.

Synthesis and evaluation of a small library of graftable thrombin inhibitors derived from (L)-arginine.

Novel piperazinyl-amide derivatives of N-alpha-(aryl-sulfonyl)-L-arginine were synthesized as graftable thrombin inhibitors, in the context of biomaterials' design. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position and the introduction of a trifluoromethyl group as XPS (X-ray Photoelectron Spectroscopy) tag on the sulfonamide moiety were evaluated in vitro against human alpha-thrombin. All the compounds of the library were found to be active at the micromolar level, as the reference TAME (N-tosyl-L-arginine methyl ester). The blood compatibilization improvement of poly(ethylene terephthalate) (PET) membrane, coated or grafted by wet chemistry treatment with one representative inhibitor of the library, was also evaluated, showing interesting decrease in blood clot formation.

{4(S)-(Piperidin-1-ylcarbonyl)-4-[3-(trifluoromethyl)phenylsulfonamido]butyl}guanidinium chloride: a model of a graftable thrombin inhibitor.

In the title compound, C18H27F3N5O3S+.Cl-, the guanidine group forms N-H...Cl hydrogen bonds, with four N...Cl distances in the range 3.164 (3)-3.337 (4) A. In the crystal packing, the cations are further linked by N-H...O and C-H...O interactions. The structure is compared with that of argatroban complexed with thrombin and is the subject of docking studies in the active site of thrombin.

Design, synthesis and evaluation of graftable thrombin inhibitors for the preparation of blood-compatible polymer materials.

Piperazinyl-amide derivatives of N-alpha-(3-trifluoromethyl-benzenesulfonyl)-L-arginine (1) were synthesized as graftable thrombin inhibitors. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position was evaluated in vitro, against human alpha-thrombin, and in blood coagulation assay. Molecular modelling (in silico analysis) and X-ray diffraction studies of thrombin-inhibitor complexes were also performed. The fixation of bioactive molecules on poly(butylene terephthalate) (PBT) and poly(ethylene terephthalate) (PET) membranes was performed by wet chemistry treatment and evaluated by XPS analysis. Surface grafting of inhibitor 1d improved the membrane hemocompatibility by reducing blood clot formation on the modified surface.

A practical molecular clip for immobilization of receptors and biomolecules on devices' surface: synthesis, grafting protocol and analytical assay.

Deposition of O-succinimidyl 4-(p-azido-phenyl)butanoate (4) onto inorganic device (FTIR-ATR crystal) or polymer material (filtration membrane) followed by irradiation at 254nm led to surface functionalisation with NHS esters. Further reaction with biomolecules allowed their covalent grafting. The reactivity of the photoactivated surfaces was assayed by two methods: (i) the coupling with 3,5-bis(trifluoromethyl)benzylamine (7) and subsequent XPS analysis; (ii) the coupling with 4,5-bis-tritiated lysine (10) and subsequent LSC measurement of the radioactivity.