Longer Spacer Research Articles

The use of N-terminal immobilization of PTH(1–34) on PLGA to enhance bioactivity

The objective of this work was to control the orientation of bioactive molecules immobilized on a biodegradable substrate to improve their accessibility for binding to cell surface receptors and, therefore, to increase bioactivity. The osteotropic peptide, parathyroid hormone (1–34) (PTH(1–34)), was used to demonstrate the approach. To this end, the intrinsic N-terminal serine residue was oxidized to create an aldehyde group that specifically bound to hydrazide-derivatized poly(lactide- co-glycolide) under neutral conditions to form a hydrazone bond. Use of dihydrazide spacers significantly increased the amount of peptide immobilized compared to simple adsorption or direct, random attachment. In probing accessibility of immobilized PTH(1–34), attachment using longer dihydrazide spacers enhanced binding of an antibody against an epitope in the N-terminal region of the peptide. The longest spacer also increased binding of a C-terminal antibody. Furthermore, substrates with peptide tethered via spacers stimulated intracellular synthesis of cAMP, with activity increasing with dihydrazide length. PTH(1–34) immobilized using the longest spacer was significantly more effective than both random binding and adsorption. Site-directed binding of bioactive peptides to surfaces presents biomolecules for binding with cells so as to enhance interaction with receptors, and therefore the approach may be useful for obtaining preferred localized tissue responses.

Modifying the structure of dinuclear ruthenium complexes with antitumor activity

AbstractIn order to modulate the structure of a recently developed series of antitumor‐active, dinuclear Ru(II)–arene compounds, complexes 1c–4c were synthesized. The complexes were modified with respect to their pyridinone moieties and the spacer linking the two metal centers. More particularly, the series of dinuclear ruthenium(II) complexes was extended to compounds with longer spacers, i.e. tetradecane and 3,7,10‐trioxotridecane, and the pyridinone ring was modified by replacing the methyl group by an ethyl group and by shifting the position of the methyl group. The organometallic ruthenium compounds were obtained from the reaction between [RuCl2(η6‐p‐isopropyltoluene)]2 and ligands 1b–4b with yields ranging from 41 to 67%. All compounds were characterized by standard methods: MS, 1H and 13C NMR spectroscopy and elemental analysis. Copyright © 2008 John Wiley & Sons, Ltd.

Structure-Activity Relationships of the Dimeric Analogues of Endomorphin-2 with Different Lengths of Spacers

In the present study, seven novel dimeric analogues of endomorphin-2 with longer spacers were designed and synthesized. Through dimerization, their affinity for delta-opioid receptor was mostly increased, especially the delta-opioid receptor preferred dimeric analogue, DEM(12). The results were confirmed by the in vitro bioassay. The structure-activity relationships were also discussed.

Adsorption Mechanism of Bilirubin on Aminated Crosslinking Microspheres of PGMA

The crosslinking microspheres of poly (glycidyl methacrylate) (PGMA) were modified chemically with aminating agents, hexanediamine and three kinds of multi-ethylene multi-amine. The effects of various factors, such as the chemical structures of the aminating agents, pH values of the medium, ionic strength, and temperature, on the adsorption property of the functional microsphers for bilirubin were examined. The adsorption mechanism of the aminated microspheres towards bilirubin was studied deeply. The experimental results showed that the aminated microspheres had strong adsorption ability for bilirubin and the adsorption capacity could reach 17.80 mg·g-1; the isotherm adsorption could be fitted by Freundlich equation satisfactorily. There were three acting forces between the aminated microspheres and bilirubin molecules, i.e., electrostatic, hydrogen bonding and hydrophobic interactions. Among them, the electrostatic interaction was dominative, and the latter two kinds exert cooperating action. As pH=6, there was the strongest electrostatic interaction between the aminated microspheres and bilirubin molecules, leading to the highest adsorption capacity. The higher ionic strength was disadvantageous to the electrostatic interaction, and salinity conduces to the weakening of the electrostatic interaction and the decreasing of the adsorption capacity. The rising of temperature was advantageous to the hydrophobic interaction, whereas unfavorable to hydrogen bonding, and the predominated one of them dominates the effect of temperature on the adsorption capacity. The adsorption ability of the aminated microspheres modified with hexanediamine was stronger than that of those aminated microspheres modified with multi-ethylene multi-amine owing to enhancement of the hydrophobic interaction and smaller steric hindrance which came from longer spacer arm.

Macromolecular Non‐Releasing Additives for Commercial Polyolefins

AbstractFour comonomers bearing a highly efficient phenolic antioxidant unit and different distance between the antioxidant moiety and the double bond have been prepared and tested in co‐polymerization with ethylene by means of three selected metallocene based catalysts. The possibility to obtain a masterbach suitable for melt blending with commercial polyolefins has been evaluated by modifying: i) the structure of the functionalized comonomer, ii) the kind of catalyst, iii) the polymerization conditions. The pair rac‐[Me2Si‐(2‐Me‐4,5‐BenzInd)2]ZrCl2 catalyst and comonomer with the longest spacer (8 methylene units) allowed the highest comonomer incorporation, while with rac‐(EBTHI)ZrCl2 catalyst the highest polymerization activity was observed. TGA analysis has been carried out on some of the copolymers in order to investigate the influence of type and amount of the comonomer on their thermal stability and to test the efficiency of the antioxidant group both in nitrogen and oxygen atmosphere.

Synthesis and properties of novel gemini surfactant with short spacer

Cationic gemini surfactant dimethylene-1,2-bis(dodecyldiethylammonium bromide), referred to as C12C2C12(Et) was synthesized, and its surface property and aggregation behavior in aqueous solution were studied. The value of γ at the critical micelle concentration (γcmc) is much smaller than that of the surfactant homologues with longer spacer. Spherical and elongated micelles were formed in the aqueous solution of this gemini surfactant, and the spherical micelles were absolutely dominant compared to the elongated micelles at our studied concentration quantitatively.

Spacer length dependence of TGBC* and SmA phases in cholesteryl and dihydrocholesteryl‐containing trimer liquid crystals

Two series of trimer liquid crystals were investigated that contain a biphenylyl central group and two cholesteryl or dihydrocholesteryl terminal mesogenic groups. Only compounds with even spacers were investigated. The dihydrocholesteryl‐containing trimers show a triply intercalated smectic A (SmA) phase when the spacer lengths are greater than 8, whereas the cholesteryl‐containing trimers exhibit this triply intercalated SmA phase when the spacer lengths are more than 6. With shorter spacers, a twist grain boundary C* (TGBC*) phase was found. This is revealed by the formation of a typical dotted square grid pattern upon cooling from the chiral nematic (N*) phase in the planar texture. The dots are spaced by a distance of about 1.5–1.8 µm. Upon cooling from the N* phase in the focal conic texture a striped pattern is observed with the same spacing. X‐ray diffraction revealed a repeat distance for the TGBC* phase that corresponds with a monolayer ordering. The results show that the weaker interaction between the dihydrocholesteryl groups compared with cholesteryl groups or longer spacers destabilize the monolayer TGBC* phase.

Influence of the Spacer of Cationic Gemini Amphiphiles on the Hydration of Lipoplexes

The impact of the length of gemini surfactant spacer on complexation and condensation of calf thymus DNA by cationic mixed phospholipid/gemini liposomes was investigated by monitoring the conformational changes of DNA by circular dichroism and the lipid hydration level by the emission characteristics of the fluorescent probe laurdan included in the lipid bilayer. The length of the spacer was shown to influence, on one hand, the hydration level and the organization of the corresponding liposomes and, on the other, the variation of lipid hydration level and the DNA conformation upon complexation. In fact, in correspondence with the longest spacer we observed more hydrated liposomes, probably organized in domains, a higher extent of dehydration promoted by the addition of DNA, and a minor extent of DNA conformational change. The physicochemical features of lipoplexes were shown to depend on the [cationic headgroup]/[DNA single base] ratio.

N-Amidothiourea based PET chemosensors for anions

Neutral N-amidothiourea based PET anion sensors bearing a pyrene fluorophore, 1-3, were synthesized and their fluorescent response toward anions was assessed. The anion quenching and binding constants were found to be much higher than those of the corresponding PET sensors bearing a simple thiourea receptor despite a higher oxidation potential of the electron donor and a relatively longer spacer (CH(2))(3) between the signal reporter and binding receptor in 1-3. This was explained in terms of a much more substantial increase in the electron donating ability of amidothiourea upon anion binding.

Pentamer is the minimum structure for oligomannosylpeptoids to bind to concanavalin A

Enzyme-linked lectin assay (ELLA) was performed for oligomannosylpeptoids, which were immobilized on microtiter plates through a streptavidin–biotin interaction. The other immobilization methods, a hydrophobic adsorption and a covalent attachment, were found inapplicable to the oligomannosylpeptoids. Penta- and hexamannosylpeptoids with a shorter or longer spacer were found to be significantly recognized by concanavalinA (ConA), while the smaller peptoids showed no bindings. A proportional relationship between the amount of bound ConA and the peptoid density on the microtiter plate was observed, indicating the absence of both cluster and overdense effects that would assist or inhibit the binding increasingly with the ligand density.

The position of yeast snoRNA-coding regions within host introns is essential for their biosynthesis and for efficient splicing of the host pre-mRNA

Genomic location of sequences encoding small nucleolar RNAs (snoRNAs) is peculiar in all eukaryotes from yeast to mammals: most of them are encoded within the introns of host genes. In Saccharomyces cerevisiae, seven snoRNAs show this location. In this work we demonstrate that the position of snoRNA-coding regions with respect to splicing consensus sequences is critical: yeast strains expressing mutant constructs containing shorter or longer spacers (the regions between snoRNA ends and intron splice sites) show a drop in accumulation of U24 and U18 snoRNAs. Further mutational analysis demonstrates that altering the distance between the 3' end of the snoRNA and the branch point is the most important constraint for snoRNA biosynthesis, and that stable external stems, which are sometimes present in introns containing snoRNAs, can overcome the positional effect. Surprisingly enough, splicing of the host introns is clearly affected in most of these constructs indicating that, at least in S. cerevisiae, an incorrect location of snoRNA-coding sequences within the host intron is detrimental to the splicing process. This is different with respect to what was demonstrated in mammals, where the activity of the splicing machinery seems to be dominant with respect to the assembly of snoRNPs, and it is not affected by the location of snoRNA sequences. We also show that intronic box C/D snoRNA recognition and assembly of snoRNPs occur during transcription when splicing sequences are recognized.

Surface and Interface Control on Photochemically Initiated Immobilization

Surface and interface properties are important in controlling the yield and efficiency of the photochemically initiated immobilization. Using a silane-functionalized perfluorophenyl azide (PFPA-silane) as the photoactive cross-linker, the immobilization of polymers was studied by adjusting the density of the surface azido groups. Dilution of the photolinker resulted in a gradual decrease in the density of surface azido groups as well as the thickness of the immobilized film. When a nonphotoactive silane was added to PFPA-silane, the film thickness decreased more rapidly, suggesting that the additive competed with PFPA-silane and effectively reduced the density of the surface azido groups. The effect of surface topography was studied by adding a nonphotoactive silane with either a shorter (n-propyltrimethoxysilane (PTMS)) or a longer spacer (n-octadecyltrimethoxysilane (ODTMS)). In most cases the long chain ODTMS shielded the surface azido groups, resulting in a more rapid decrease in film thickness as compared to PTMS treated under the same conditions. As the density of the surface azido groups decreased, the immobilized polymer changed from smooth films to patched structures and, eventually, single polymer molecules.

Interactions between bovine serum albumin and gemini surfactant alkanediyl‐α, ω‐bis(dimethyldodecyl‐ammonium bromide)

Interactions between bovine serum albumin (BSA) and cationic gemini surfactant alkanediyl-alpha,omega-bis(dimethyldodecyl-ammonium bromide) (12-n-12, n=3, 4, 6) in aqueous solution have been investigated by measuring fluorescence, UV-vis transmittance, dynamic lighting scattering, and circular dichroism. Compared to a traditional surfactant dodecyltrimethylammonium bromide (DTAB), 12-n-12 interacts with BSA more strongly. With increasing concentration, 12-n-12 first binds specifically onto BSA leading to the unfolding and aggregation of BSA, and the decrease in alpha-helix content; and then forms micelle-like complexes along the unfolded BSA chains. A gemini surfactant with a longer spacer has a larger effect on BSA unfolding due to a stronger hydrophobic interaction.

The impact of the intrinsic and extrinsic resistances of double gate SOI on RF performance

In this paper, the analogue performance of a 65nm node double gate SOI (DGSOI) is qualitatively investigated using MixedMode simulation. The intrinsic resistance of the device is optimised by evaluating the impact of the source/drain engineering using variation of spacers and doping profile on the RF key figures of merit such as fT, and fMAX. It is evident that longer spacers, which approach the length of the gate offer better RF performance irrespective of the profile as long as the doping gradient at the gate edge is <7nm/decade. Analytical expressions, which reflect the dependence of fT, and fMAX on extrinsic source, drain and gate resistances RS, RD and RG have been derived. While RD and RS have equal effect on fT, RD appears to be more influential than RS in reducing fMAX. The sensitivity of fMAX to RS and RD. has been shown to be greater than to RG.

Photoinduced alignment of azobenzene side‐chain polymers with short spacer: Biaxial orientation and fast response

AbstractSide‐chain azobenzene‐containing liquid crystalline polymer (ALCP) of Poly(6‐[4‐(4‐cyanophenylazo)phenoxy] x‐methylene methacrylate)(Px, x is 2 or 6) was synthesized and used to study its photoinduced alignment behavior irradiated by a linearly polarized laser at room temperature. The relationships between transmittance and irradiation time as well as transmittance and various incident angles were studied in detail. The oversaturation phenomenon of P2 film was found to be higher than 1 mW/cm2 under irradiation energy density. A model of the biaxial orientation was introduced to explain the phenomenon: it is the rigid short spacer that makes it possible for mesogen to coexist in a way of out‐of‐plane and in‐plane orientation (biaxial orientation), in which the type of photoinduced motions is a single mesogen motion in the film of P2, whereas in the film of P6 with longer spacer, the motion is a microdomain motion. The whole domain motion restricted the out‐of‐plane orientation, which shows a slow orientation rate and all mesogens aligned within the film plane. A novel dynamic fitting was also presented to describe the orientation of P2, which was discussed in terms of the fitting parameters. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1378–1384, 2006

Molecular Recognition: Comparative Study of a Tunable Host–Guest System by Using a Fluorescent Model System and Collision‐Induced Dissociation Mass Spectrometry on Dendrimers

Host-guest interactions between the periphery of adamantylurea-functionalized dendrimers (host) and ureido acetic acid derivatives (guest) were shown to be specific, strong and spatially well-defined. The binding becomes stronger when using phosphonic or sulfonic acid derivatives. In the present work we have quantified the binding constants for the host-guest interactions between two different host motifs and six different guest molecules. The host molecules, which resemble the periphery of a poly(propylene imine) dendrimer, have been fitted with an anthracene-based fluorescent probe. The two host motifs differ in terms of the length of the spacer between a tertiary amine and two ureido functionalities. The guest molecules all contain an acidic moiety (either a carboxylic acid, a phosphonic acid, or a sulfonic acid) and three of them also contain an ureido moiety capable of forming multiple hydrogen bonds to the hosts. The binding constants for all 12 host-guest complexes have been determined by using fluorescence titrations by monitoring the increase in fluorescence of the host upon protonation by the addition of the guest. The binding constants could be tuned by changing the design of the acidic part of the guest. The formation of hydrogen bonds gives, in all cases, higher association constants, demonstrating that the host is more than a proton sensor. The host with the longer spacer (propyl) shows higher association constants than the host with the shorter spacer (ethyl). The gain in association constants are higher when the urea function is added to the guests for the host with the longer spacer, indicating a better fit. Collision-induced dissociation mass spectrometry (CID-MS) is used to study the stability of the six motifs using the corresponding third generation dendrimer. A similar trend is found when the six different guests are compared.

Physical Properties of Siloxane Containing Oxycyanobiphenyl Derivatives for Smectic-A Device Applications

ABSTRACT In this paper we report on a homologous series of oxycyanobiphenyl liquid crystals with pentamethyldisiloxane units substituted onto the end of the alkoxy chain. We present fast switching times in the order of milliseconds, threshold voltages of ∼ 2 V/μm, and show that these properties are relatively temperature independent. Measurements were made by means of electro-optical microscopy. Experiments were conducted in both the high frequency (dielectric) mode and also in the low frequency (scattering) mode. We find that the measured properties are dependent upon the length of the alkoxy chain and that the longer spacer chains, n ≥ 8, give low threshold voltages, fast response times and a distinct high frequency-low frequency crossover mode.

Structural Fine-Tuning of (−Donor−spacer−acceptor−spacer−)n Type Foldamers. Effect of Spacer Segment Length, Temperature, and Metal-Ion Complexation on the Folding Process

The synthesis of a series of polymers (PDA–nOE) containing an alternating arrangement of electron rich (donor) and electron deficient (acceptor) aromatic units, which are linked by flexible oligo(oxyethylene) (nOE) spacers, is reported. The length of the oligo(oxyethylene) spacer was varied from tetra(oxyethylene) (n = 4) to hexa(oxyethylene) (n = 6), to examine the relative propensities of these polymers to form folded structures by virtue of intrachain charge-transfer interactions between the adjacent donor and acceptor units. Comparison of the proton NMR and UV−visible spectra of the three different polymers clearly reveals that PDA–4OE, which has the shortest tetra(oxyethylene) spacer, exhibits the greatest propensity to fold in the nascent form. A significant upfield shift of the aromatic protons upon lowering of temperature confirmed this greater tendency of the PDA–4OE to fold; the spectra of polymers with longer spacers, on the other hand, exhibited a very weak temperature dependence indicating their sluggishness to fold in nascent form. However, in the presence of suitable alkali-metal ions (or a polar solvent), the spectra of the polymers with longer oligo(oxyethylene) spacers also exhibit a much stronger temperature dependence (similar to the PDA–4OE case), implying the occurrence of a metal-ion (and solvophobic effect) assisted formation of folded structures. These NMR studies corroborate well with similar variable temperature UV−visible spectral studies, wherein the intensities of the D−A charge-transfer band is monitored as a signature of the folded structure; there were, however, some distinct differences in the nature of the variation in the case of nascent polymer samples that appear to reflect the differences in sensitivities of the two spectral techniques to the folding process. In an effort to better understand the folding process, model compounds of the type donor−spacer−acceptor and analogous DAD and ADA were synthesized. Comparison of the spectral changes seen in model compounds, both as a function of temperature and during alkali-metal ion titrations, with those seen in the analogous polymers helped confirm that the folded structures in the polymer clearly must involve intrachain charge-transfer interactions that exceeds simple pairing of adjacent donor and acceptor units; i.e., the acceptors in the folded polymer are sandwiched between donors and vice versa, thereby forming extended stacks.

Influence of Side‐Chain Structure and Irradiation Condition on Photoalignment of Ladder‐Like Polysiloxane Films

AbstractIn this paper we consider the photo‐induced aligning capability of various ladder‐like polysiloxane‐based photoalignment films—which could be used in liquid‐crystal displays—bearing different photoreactive side chains, i.e., laterally grafted cinnamate/azobenzene‐based dual photoreactive side chains with a short or longer spacer, and terminally fixed coumarin‐containing side chains. Results from polarized optical microscopy (POM), Fourier‐transform infrared (FTIR) spectroscopy, surface‐enhanced Raman scattering (SERS), atomic force microscopy (AFM), etc., are integrated to elucidate the influence of side‐chain structure and the irradiation conditions on the photoalignment of ladder‐like polysiloxane films. It is demonstrated that the film containing the dual photoreactive group with a longer spacer exhibits better alignment properties. Reasonably, the concerted photoreactions of the dual photoreactive group and the longer spacer are beneficial to the cooperative motion of chromophores at the “domain level”, resulting in improved alignment facility and stability. The complicated effects of irradiation conditions and moderate annealing are also discussed. High‐quality alignment of the polysilsesquioxane (LPS)‐based photoalignment film LPS‐CA11 with a longer spacer between the LPS main chain and cinnamoyl/azobenzene side chains can be achieved only within an optimal range of exposure (5–8 J cm–2), while the pretilt angles can be adjusted in the range 0.5°–7° by varying the incident light intensity. Additionally, moderate annealing before and after illumination can markedly improve the alignment uniformity by self‐healing of defects.

Controlled Variation of Spacer Segment in Hyperbranched Polymers: From Densely Branched to Lightly Branched Systems

A series of hyperbranched polyethers containing different types (and lengths) of spacer segments that link the branch points were prepared by solvent-free melt transetherification methodology. Three types of spacers, namely n-alkylene, cycloalkylene, and oxyethylene, were incorporated into the hyperbranched structures in order to examine the role of spacer length (and flexibility) on the relative compactness of the chain conformation as well as to study its effect on their $T_g$. The distinctive feature of this investigation is that the branching density (number of branch-points per unit volume) is varied in controlled manner by utilizing $AB_2$-type monomers that contain spacer segments of different lengths. GPC studies using dual detector (RI-DV) system revealed that most of the polymers were of fairly high molecular weight, with $M_w$ values ranging from 24 000 to 90 000. It is seen that as the branching density decreases, i.e., when the spacer segment length increases, the Mark-Howink exponent a increases; for instance, it increased from 0.37 for the polymer without spacer to 0.54 in the case of the polymer having 10-carbon spacer segment. This suggests that the relative compactness of the hyperbranched structures diminishes with increasing length of the spacer segment and might be expected to approach the behavior of linear macromolecules for even longer spacers. Furthermore, comparison of the molecular weights of several fractionated samples, determined by both the standard polystyrene calibration plot as well as by the universal calibration plot, reveals that the extent of molecular weight underestimation using the PS calibration becomes significant only at higher molecular weights. Thus, as seen in dendrimers, in hyperbranched polymers also compact structures are formed only beyond certain molecular weight. The glass transition temperatures of the hyperbranched polymers were seen to decrease monotonically with increasing spacer length within each series, and hyperbranched structures with relatively flexible spacers exhibited lower $T_g$ values when compared to ones with relatively rigid spacers of similar length.