The net nanoscale interaction between a probe tip covalently bound with the blood plasma protein human serum albumin (HSA) and a surface of end-grafted poly(ethylene oxide) (PEO) mushrooms (Mn ∼ 50K, Flory radius RF ∼ 9 nm, contour length Lcontour ∼ 393 nm) was measured directly on approach (loading) and retract (unloading) in aqueous buffer solution using the technique of high-resolution force spectroscopy (HRFS). On approach of the HSA probe tip to the PEO surface, a monotonic nonlinear repulsive net force was observed for tip−sample separation distances of <30 nm, the magnitude of which is much larger than that predicted by either electrostatic double layer or steric theories based on configurational entropy. Attractive contacts between the PEO and HSA are formed during experimentation, enabling the tethering and extension of individual PEO chains on retraction. The mean binding force of the HSA probe tip to individual PEO chains was determined to be 〈Fadh〉 = 0.06 ± 0.10 nN or 〈Fadh/Radius〉 = 0.9 ± 1.6 mN/m (where Radius is the end radius of the probe tip as measured by scanning electron microscopy). By combining the results of HRFS experiments with theoretical approaches, we have shown that this technique is a valuable tool for understanding biocompatibility at the nanoscale and can provide valuable information that may be used as a guideline for the design of improved synthetic macromolecular systems for future biomedical applications.
To study the molecular origins of hemocompatibility, the blood plasma protein human serum albumin (HSA) was covalently grafted to a nanosized probe tip at the end of a soft, microfabricated cantilever force transducer. The net force versus separation distance between the HSA-modified probe tip and three different model surfaces, including (1) gold; (2) a hydrophobic, CH3-terminated alkanethiol self-assembling monolayer (SAM); and (3) a hydrophilic, COO --terminated alkanethiol SAM in aqueous sodium phosphate buffer solution (PBS, ionic strength (IS) ) 0.01 M, pH ) 7.4), was recorded and compared to the values of various theoretical models. The approach interaction of the HSA probe tip on the COO --terminated SAM and Au substrates was found to be purely repulsive for D < 15 nm, nonlinear with decreasing separation distance, and consistent with electrostatic double layer repulsion. The approach interaction of the HSA probe tip on the CH3-terminated SAM substrate was found to be purely attractive, long range (D < 80 nm), nonlinear with decreasing separation distance, and much greater in magnitude and range than that known for van der Waals interactions between hydrocarbon SAMs terminated with hydrophilic chemical groups on Au. Large adhesive energies were observed for the HSA probe tip on both the CH3-terminated SAM and Au surfaces (e-29 mN/m, -22 to -73kBT/protein), while smaller adhesive energies were observed on the COO --terminated SAM surface (e -4.9 mN/m, -5.3 to -12kBT/protein). It was shown that short-range adhesive contacts between the HSA chain segments and these surfaces give rise to energy dissipating mechanisms, such as HSA entropic molecular elasticity and enthalpic unfolding forces (deformation and rupture of noncovalent intramolecular bonds) and noncovalent bond rupture of the HSA chain segments adsorbed to the surface. IntroductionThe interaction between the surface of an implanted artificial medical device and blood typically results in nonspecific, noncovalent surface adsorption of blood plasma proteins followed by platelet adhesion and activation, initiation of the coagulation cascade, and thrombus formation. 1,2 In the absence of transport limitations, the interaction potential between the protein and the surface as a function of separation distance, U(D), will determine whether a protein will adsorb and at what rate. U(D) is typically a superposition of numerous nonspecific repulsive (e.g. electrostatic counterion double layer, steric, hydration, etc.) and attractive (e.g. van der Waals, hydrophobic, H-bonding, ionic, etc.) components that can lead to complicated functional forms that vary with the strength and range of the constituent interactions. 3,4 Generally, improved protein resistance can be achieved by maximizing repulsive interactions and minimizing attractive ones. Subsequent stages of protein adsorption become increasingly complex and depend on the conformation, orientation, and mobility of the adsorbed proteins, the time-scale of conformational changes, protein exchange and desorp...
Dicyanoarenes and -alkenes typically react with alkali metal alkoxides in alcohols to give molecular cyclotetramers, the best known example of these being the phthalocyanines. 1 In marked contrast to the prior literature, 1 we now report that 2-benzylidene-4,5-dicyano-1,3-dithiole (1) reacts with lithium n-butoxide in n-butanol at reflux to give a new polymer with a conjugated backbone structure.Previously available as a minor reaction byproduct, 2 1 was synthesized in the present work from the known diester 3 by conversion to a bis-amide, mp 248-249 °C (dec), using aqueous NH 3 . The amide was reacted with POCl 3 in pyridine to give 1, a red-orange solid, mp 146-147 °C, completely characterized by infrared, 1 H, and 13 C NMR spectra, mass spectrum, and elemental analysis. In tetrahydrofuran (THF) solution 1 exhibits the following electronic spectrum: λ max , 460 nm (log ) 3.24). The fluorescence spectrum of 1 in the same solvent exhibits a maximum at 530 nm when excited with 460 nm light.In refluxing n-butanol, 1 and n-BuOLi react over 2-3 h to give a dark blue solution from which a blue-black amorphous (by X-ray powder diffraction) solid 2 is isolated, after hydrolytic workup in chloroform and 10% HCl, in 53% yield; mp (capillary) 170 °C (dec). In the absence of butoxide, 1 is recovered unchanged from refluxing n-butanol. From the broad resonances of 1 H NMR and molecular weight estimation (weight-average MW 14 000-60 000 (GPC, versus polystyrene standards), M w /M n ) 2.01), 2 is found to be polymeric, and its color and electronic spectrum in THF solution (λ max 530-550 nm, tailing past 1000 nm) indicate a conjugated backbone. The absorption spectrum of 2 in THF is shown in Figure 1. Absorption spectra of 2 in dimethylformamide or dimethyl sulfoxide give broad maxima at 575-580 nm, with shoulders at 630 and 850 nm, with tailing past 1000 nm. It is not likely that the long absorption tail is due to scattering from insoluble polymer. Solutions were filtered before spectra were recorded, and in the solutions used for spectra, no precipitates formed on standing for times in excess of a month. Similar polymers were isolated from reaction of 1 with sodium pentoxide in refluxing n-pentanol and in refluxing (dimethylamino)-2-propanol.An approximate structure for 2, depicted in Figure 2, is proposed on the basis of elemental analysis, IR, and 1 H and 13 C NMR spectra. The atomic ratio of S:N is unity and indicates the preservation of the 1,3-dithiole ring during the polymerization. The absence of a -CN stretch in the IR spectrum and lack of a -CN resonance near 115 ppm in the 13 C NMR spectrum, along with the intense visible and near-infrared electronic spectrum, suggest a conjugated backbone structure formed by cyclopolymerization across the dicyanoalkene moiety.
C o n j u g a t e d M a t e r i a l s : P r o s p e c t s f o r S y n t h e s i s U s i n g C a r b o h y d r a t e R e a g e n t s Abstract: General considerations related to the use of sugars and closely related compounds as reagents for molecular and macromolecular synthesis are presented. For the first time, we have used unprotected carbohydrates to initiate polymerizations. A variety of dicyanoalkenes and -arenes react with sugars in the presence of alkali to give conjugated polymers. Both cyclopolymerization and polymerization at only one of two cyano groups are observed, and some qualitative mechanistic issues related to these observations are discussed. In some cases, a sugar alkoxide is the active initiating reagent. Characterization of the resulting polymers is reported. Alkaline sugar reagents have also been used in Knoevenagel reactions to synthesize CN-PPV oligomers and a related conjugated polymer in good yields. The use of the polysaccharide chitosan as a polycation allows the absorption spectrum of the polythiophene HPURET to shift to longer wavelengths than other polycations in electrostatically assembled films.
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