Recognition Polymers

From the universe of polymeric materials which appear in biology and medicine we select for discussion that set whose principal function is to recognize and respond appropriately to specific substances in their environment. They may be 1.2, 2.2, or 3 dimensional shapes such as messenger RNA, cellulose acetate membranes, or artificial esophagi. They may function by recognizing the difference between right and wrong chemical species and responding by binding the correct ones and rejecting the wrong ones, e.g., enzymes and their substrates, codons and their anticodons. What happens after recognition and response is not of interest at the moment, e.g., the catalytic effect of the enzyme on the bound substrate or the codonanticodon binding effect on protein synthesis.

Another example is in the chemical senses where there is sketchy evidence that proteins are involved in recognizing tastants. This could be done by having a protein on the tongue bind all tastants (rather close contact is required to make fine distinctions) and then recognize them by very intimate contacts and sending signals to the brain for conscious recognition. Alternatively, each taste modality may have a protein that excludes all but one type and generates only one signal for the CNS.

Another important class are antibodies that recognize their own antigens out of about 10⁴ different ones and complex with them and exclude the others. A model for antigen-antibody interaction must account for the non-binding of nonantigens as well as the much simpler case of the binding of the antigen.

Another class are the permselective membranes that recognize some species and let them pass while recognizing others and not let them pass. A final class to be discussed will be implant polymers which have an un-desired ability to recognize and bind platelets.

The question we are asking is whether it is possible to establish general principles in chemical physics that govern these different types of molecular recognition so that the principles could be incorporated into polymer design. Recent advances in “intermolecular” force theory suggests that this goal is achievable in the foreseeable future. Intermolecular has been put in quotes because when two molecules are in sufficiently close contact to recognize one another they probably have an appreciable exchange term and are therefore not two molecules but one.

The recent advances referred to involve computer simulation of complex formation using the new 1-4-6-12 potential forms corresponding to a long range (R^?1) coulombic electrostatic interaction, a medium range (R^?4) electrostatic-induced dipole attraction, a short range (R^?6) dispersive attraction, and a very short range (R^?12) orbital overlap repulsion. In the cases of interest, e.g., in an aqueous environment, all four terms are important and statements such as “the binding is purely electrostatic,” i.e., all R^?1, are misleading as well as wrong (since even ions need the R^?12 repulsion to keep them at their equilibrium distance). Discussions of permeability in terms of “pore sizes” is equally limiting for it implies that only the R^?12repulsion is appreciable. The fallacy of using competitive equilibria to determine the relative contributions of terms will be discussed. The im: portant use in biology of “other contacts” within the system to give a variable base line so that the typical binding-no binding discrimination can be made with attraction-less attraction rather than the more awkward attraction-repulsion potentials will also be discussed.     

On the Effect of Organic Substitution of Silicon Alkoxides in Poly(Vinyl Acetate) Organic-Inorganic Composites

Abstract

Organic-inorganic composites (OICs) were prepared via the in-situ polymerization of an organically (phenyl) substituted trialkoxysilane, phenyltriethoxysilane (PhTEOS), in the presence of poly(vinyl acetate) (PVAc). The mechanical reinforcement above T _g previously observed in OICs of unfunctionalized organic polymers such as PVAc with acid catalyzed in-situ polymerized tetraalkoxysilane was not observed when the tetraalkoxysilane was replaced with PhTEOS. Although both systems are optically transparent and both exhibit a high degree of hydrogen bonding between the carbonyl of PVAc and the residual hydroxyls of the silicate, the polymerization of the alkoxide is different. The tetra-functional alkoxide polymerizes to form a load-supporting silicate network, leading to a high plateau in the tensile modulus above T _g, whereas the trifunctional alkoxide reacts to form primarily low molecular weight oligomers. These increase the T _g of the PVAc but do not provide mechanical reinforcement.     

Embedding hypertrees into steiner triple systems

In this paper, we are interested in the following question: given an arbitrary Steiner triple system on vertices and any 3‐uniform hypertree on vertices, is it necessary that contains as a subgraph provided ? We show the answer is positive for a class of hypertrees and conjecture that the answer is always positive.     

Plate-based diversity subset screening: an efficient paradigm for high throughput screening of a large screening file

The screening files of many large companies, including Pfizer, have grown considerably due to internal chemistry efforts, company mergers and acquisitions, external contracted synthesis, or compound purchase schemes. In order to screen the targets of interest in a cost-effective fashion, we devised an easy-to-assemble, plate-based diversity subset (PBDS) that represents almost the entire computed chemical space of the screening file whilst comprising only a fraction of the plates in the collection. In order to create this file, we developed new design principles for the quality assessment of screening plates: the Rule of 40 (Ro40) and a plate selection process that insured excellent coverage of both library chemistry and legacy chemistry space. This paper describes the rationale, design, construction, and performance of the PBDS, that has evolved into the standard paradigm for singleton (one compound per well) high-throughput screening in Pfizer since its introduction in 2006.     

Quasi Monte Carlo-based isotropic distribution of gradient directions for improved reconstruction quality of 3D EPR imaging

In continuous wave (CW) electron paramagnetic resonance imaging (EPRI), high quality of reconstructed image along with fast and reliable data acquisition is highly desirable for many biological applications. An accurate representation of uniform distribution of projection data is necessary to ensure high reconstruction quality. The current techniques for data acquisition suffer from nonuniformities or local anisotropies in the distribution of projection data and present a poor approximation of a true uniform and isotropic distribution. In this work, we have implemented a technique based on Quasi-Monte Carlo method to acquire projections with more uniform and isotropic distribution of data over a 3D acquisition space. The proposed technique exhibits improvements in the reconstruction quality in terms of both mean-square-error and visual judgment. The effectiveness of the suggested technique is demonstrated using computer simulations and 3D EPRI experiments. The technique is robust and exhibits consistent performance for different object configurations and orientations.     

Silver/polystyrene-coated hollow glass waveguides for the transmission of terahertz radiation

We have applied techniques developed for IR waveguides to fabricate Ag/polystyrene (PS) -coated hollow glass waveguides (HGWs) for transmission of terahertz radiation. A loss of 0.95 dB/m at 119 microm (2.5 THz) was obtained for a 2 mm bore, 90 cm long Ag/PS HGW. We found that TE modes are supported in HGWs with thin PS films, while hybrid (HE) modes dominate when PS film thickness increases. The lowest losses are obtained for the thicker PS films and the propagation of the HE modes.     

Comparison of Three Plasma Sources for Ambient Desorption/Ionization Mass Spectrometry

Plasma-based desorption/ionization sources are an important ionization technique for ambient surface analysis mass spectrometry. In this paper, we compare and contrast three competing plasma based desorption/ionization sources: a radio-frequency (rf) plasma needle, a dielectric barrier plasma jet, and a low-temperature plasma probe. The ambient composition of the three sources and their effectiveness at analyzing a range of pharmaceuticals and polymers were assessed. Results show that the background mass spectrum of each source was dominated by air species, with the rf needle producing a richer ion spectrum consisting mainly of ionized water clusters. It was also seen that each source produced different ion fragments of the analytes under investigation: this is thought to be due to different substrate heating, different ion transport mechanisms, and different electric field orientations. The rf needle was found to fragment the analytes least and as a result it was able to detect larger polymer ions than the other sources. Figure

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Sterically Shielded Heptamethine Cyanine Dyes for Bioconjugation and High Performance Near‐Infrared Fluorescence Imaging

The near‐infrared window of fluorescent heptamethine cyanine dyes greatly facilitates biological imaging because there is deep penetration of the light and negligible background fluorescence. However, dye instability, aggregation, and poor pharmacokinetics are current drawbacks that limit performance and the scope of possible applications. All these limitations are simultaneously overcome with a new molecular design strategy that produces a charge balanced and sterically shielded fluorochrome. The key design feature is a meso‐aryl group that simultaneously projects two shielding arms directly over each face of a linear heptamethine polyene. Cell and mouse imaging experiments compared a shielded heptamethine cyanine dye (and several peptide and antibody bioconjugates) to benchmark heptamethine dyes and found that the shielded systems possess an unsurpassed combination of photophysical, physiochemical, and biodistribution properties that greatly enhance bioimaging performance.     

Conditions for secondary particle formation in emulsion polymerization systems

A simple means is deduced for determining conditions for secondary particle formation in emulsion polymerization systems in systems where the amount of added surfactant is below the cmc. A new radical formed from initiator in the aqueous phase will undergo some polymerization with aqueous-phase monomer, but must have three possible eventual fates: aqueous-phase termination, entry into a preexisting particle, or creation of a new particle. The means for determining the onset and extent of secondary nucleation is to modify HUFT theory to take into account a successful model for entry [ Macromolecules, 24, 1629 (1991)] which states that entry occurs if and only if the aqueous-phase radical has achieved a critical degree of polymerization z. Particle formation below the cmc is by homogeneous/coagulative nucleation which (if coagulation is ignored) gives an upper bound to the rate of formation of precursor particles; these are of a degree of polymerization J_crit > z. The resulting equations are readily solved, and require only a knowledge of the aqueous-phase propagation and termination rate coefficients (the latter is very high: ca. 10⁹ dm³ mol⁻¹ s⁻¹ for termination between the very small radicals), z and j_crit. Easily applied means are given for estimating all these quantities. The treatment gives good accord with experimentally observed conditions for the onset of secondary nucleation in low-surfactant systems (including taking in situ micellization into account).