Alfonso Bentolila

Synthesis and heparin‐like biological activity of amino acid‐based polymers

Biological macromolecules are important regulators of physiological functions. Most of the biologically active macromolecules are charged linear polymers like some proteins, DNA and glycosaminoglycans (GAG). Heparin, the first GAG applied in medicine, is a natural polyanion composed of repeating disaccharide units of glucosamine and uronic acid. The amino and hydroxyl groups of the glucosamine units are partially sulfated. Heparin is a potent anticoagulant, and is also active as an antimethastatic and antiproliferative agent. Sulfatation of other polysaccharides such as laminarin yielded very potent new anticoagulans. It was hypothesized that macromolecules based on N-acryl L-amino acids bearing hydrophobic or charged side groups, such as NH2, COOH, SH, OH and phenols, arranged into a configuration determined by the chirality of the amino acid α-carbon, may express heparin-like biological activities. Homo-poly(N-acryl amino acids) were synthesized from the corresponding monomers. Polymers with different charge densities, nature of the amino acid side group, stereoselectivity and polymeric backbone were tested for their activity as anticoagulants, heparanase inhibition agents, and to basic fibroblast growth factor (b-FGF) release agents bound to the extracellular matrix (ECM). The type of amino acid, the polymer backbone, the charge density and distribution strongly affect the biological activity exerted by these polyanions. All polymers being active either as heparanase inhibitors and/or as b-FGF release agents have at least a negative charge density of 1 per amino acid residue. Polymers bearing hydrophilic side chains that inhibited heparanase, i.e., hydroxyproline, glycine and serine, did not release b-FGF from ECM. The absence of high acidic sulfate-ester groups existing in heparin (hydrophilic) must be compensated by some kind of lipophilic interactions between the polyanion and b-FGF in order to effectively compete with heparan sulfate proteoglycanes, causing its release from ECM. Heparanase inhibitors may have clinical applications in preventing tumor metastasis and inflammatory/autoimmune processes due to the involvement of this enzyme in the extravasation of blood-borne tumor cells and activated cells of the immune system. Molecules that release ECM-bound b-FGF may be applied to accelerate neovascularization and tissue repair. Copyright

Morphological, spectral and chromatography analysis and forensic comparison of PET fibers

Poly(ethylene terephthalate) (PET) fiber analysis and comparison by spectral and polymer molecular weight determination was investigated. Plain fibers of PET, a common textile fiber and plastic material was chosen for this study. The fibers were analyzed for morphological (SEM and AFM), spectral (IR and NMR), thermal (DSC) and molecular weight (MS and GPC) differences. Molecular analysis of PET fibers by Gel Permeation Chromatography (GPC) allowed the comparison of fibers that could not be otherwise distinguished with high confidence. Plain PET fibers were dissolved in hexafluoroisopropanol (HFIP) and analyzed by GPC using hexafluoroisopropanol:chloroform 2:98 v/v as eluent. 14 PET fiber samples, collected from various commercial producers, were analyzed for polymer molecular weight by GPC. Distinct differences in the molecular weight of the different fiber samples were found which may have potential use in forensic fiber comparison. PET fibers with average molecular weights between about 20,000 and 70,000 g mol(-1) were determined using fiber concentrations in HFIP as low as 1 μg mL(-1). This GPC analytical method can be applied for exclusively distinguish between PET fibers using 1 μg of fiber. This method can be extended to forensic comparison of other synthetic fibers such as polyamides and acrylics.

Structure and Biological Activity of Heparinoid

Heparin is a biogenic anionic charged sulfated polysaccharide that has a range of desired activities including inhibition of tumor metastasis and inhibition of restenosis. However, its clinical use is limited to treating blood-clotting disorders. Anionic macromolecules called heparinoids have been investigated with the objective of developing heparin-like molecules with reduced anti-coagulant activity and selective anti-metastasis and anti-restenosis activity. This mini-review summarizes the synthesis and biological activity of the main synthetic heparinoids reported in the past three decades.

THE REACTION OF BENZOYLPHOSPHONIC ACID WITH THIONYL CHLORIDE. THE FORMATION OF BENZOYLPHOSPHONIC DICHLORIDE AND P,P′-DIBENZOYLPYROPHOSPHONIC DICHLORIDE

Abstract The reaction of benzoylphosphonic acid (3) with thionyl chloride leads to the formation of benzoylphosphonic dichloride (5) and P,P′-dibenzoylpyrophosphonic dichloride (6). These products were identified by 31P nmr spectra and through their products of alcoholysis with 2-propanol.

Blood or not blood—That is the question. A non-destructive method for the detection of blood-contaminated fingermarks

Working in crime scenes presents a challenge to the forensic scientist, as some surfaces, such as floors and walls, cannot be transferred to the lab for further development and must, therefore, be processed at the crime scene itself. Two main types of latent fingermarks may be encountered in crime scenes: amino acids based and blood contaminated. One of the most common reagents, which are able to develop both types of fingermarks on porous surfaces, is ninhydrin. As blood contaminated fingermarks may be crucial in connecting the suspect to the crime it is important to be able to distinguish between them and natural fingermarks. More than a decade of experience in crime scene investigations led to the understanding that there is a clear visual distinction between natural and blood contaminated fingermarks that are developed by ninhydrin. This study attempted to translate the visual difference into a mobile, non-destructive spectrophotometric method that can be used in crime scenes. Three independent spectrophotometric approaches were examined. The first showed a clear difference between the UV-vis spectra of the solution of blood and ninhydrin versus that of Ruhemanns purple. The second introduced another method in the solid phase to better simulate a real exhibit found in crime scenes. Once establishing the scientific foundation for the visible difference, a third technique for colour measurements was used in order to provide a potentially fast, quantitative, accurate and non-destructive field test for blood determination at the crime scene.