Quantification of retinoid concentrations in human serum and brain tumor tissues

Retinoic acid signaling is essential for central nervous system (CNS) differentiation and appears to be impaired in tumors. Thus far, there are no established methods to quantify relevant retinoids (all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis retinoic acid, and retinol) in human brain tumors. We developed a single step extraction and quantification procedure for polar and apolar retinoids in normal tissue, lipid-rich brain tumor tissues, and serum. This quantification procedure is based on high performance liquid chromatography (HPLC) with diode-array detection (DAD) using all-trans-acitretin as an internal standard and extraction by liquid–liquid partition with ethyl acetate and borate buffer at pH 9. Recovery with this extraction procedure was higher than earlier (two-step) liquid–liquid extraction procedures based on hexane, NaOH, and HCl. The overall quantification procedure was validated according to Food and Drug Administration (FDA) guidelines and fulfilled all criteria of accuracy, precision, selectivity, recovery, and stability. The overall method accuracy varied between −5.6% and +5.4% for serum and −3.8% and +6.2% for tissues, and overall precision ranged from 3.1% to 6.9% for serum and 2.1% to 8.3% for tissues (%CV batch-to-batch). The lower limit of quantification for all compounds in tumor tissue (and serum) was 3.9 ng g⁻¹ (ng mL⁻¹). Using this assay, photodegradation of the retinoids was evaluated and endogenous polar and apolar retinoids were quantified in sera and brain tumor tissues of patients and compared with serum and tonsil tissue concentrations of controls. It may thus serve as a suitable method for the characterization of retinoid uptake and metabolism in the respective compartments.     

Engineering reactions in crystalline solids: predicting photochemical decarbonylation from calculated thermochemical parameters

A detailed thermochemical analysis of the alpha-cleavage and decarbonylation reactions of acetone and several ketodiesters was carried out with the B3LYP/6-31G* density functional method. The heats of formation of several ground-state ketones and radicals were calculated at 298 K to determine bond dissociation energies (BDE) and radical stabilization energies (RSE) as a function of substituents. Results show that the radical-stabilizing abilities of the ketone substituents play a very important role on the thermodynamics of the alpha-cleavage and decarbonylation steps. An excellent correlation between calculated values and previous experimental observations suggests that photochemical alpha-cleavage and decarbonylation in crystals should be predictable from knowledge of excitation energies and the RSE of the substituent.     

Study on resolution capacity and secondary mechanisms of three different TSK gels for organic SEC

A comparative study on the elution behavior in size-exclusion chromatography (SEC) of three polymeric TSK gel packings, named H, H(HR), and H(XL) types, is performed. The deviations of the universal calibration (u.c.) curves of seven solvent-polymer systems show evidence that the existence of secondary effects accompanying the main SEC mechanism. These secondary mechanisms are a consequence of the binary enthalpic interactions between the different components of the chromatographic system, such as polymer-solvent, polymer-gel and solvent-gel. However, in the present case, the observed deviations from a unique u.c. curve can mainly be attributed to adsorption of polymeric solutes (analytes) onto the residual moieties of the gel surfaces, (i.e., to polymer-gel interactions). These enthalpic interactions can be quantitated by the values of the distribution coefficient, Kp, which follows the order: Kp (gel H(XL)) > Kp (gel H(HR)) > Kp (gel H). Moreover, the specific resolution of the three types of packings is also estimated, and its comparison yields that Rsp (gel H(HR)) > Rsp (gel H(XL)) > Rsp (gel H), in good agreement with their increasing particle size and decreasing crosslinking degrees. Finally, the errors and inaccuracies committed on the estimation of the sample average molar masses from their respective calibration curves serves the assessment that the packing with lesser secondary mechanisms is the H-type.     

A convenient synthesis of novel pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazinones from imidazo[1,2‐a]pyridines

The imidazo[1,2‐a]pyridine system was investigated as a synthon for the building of very attractive fused triazines, a planar, angular tri‐heterocycle with potential biological activity. Thus ethyl 3‐nitroimidazo[1,2‐a]pyridine‐2‐carboxylate was treated with ammonia or with an excess of primary amines to generate the corresponding substituted nitro carboxamidoimidazopyridines. The nitro substituent in the latter products, was reduced to yield 3‐amino‐2‐carboxamidoimidazo[1,2‐a]pyridine derivatives, which in turn were treated with nitrous acid to furnish 1‐oxo‐2‐substituted pyrido(1′,2′:1,2)imidazo[5,4‐d]‐1,2,3‐triazines.     

Spectrofluorimetric Method for the Determination of Aluminum with Alizarin Red PS

 A simple and direct spectrofluorimetric method has been developed for the determination of aluminum using alizarin red PS (1,2,4-trihydroxy 9,10-anthraquinone-3-sulfonic acid). The method is based on the strong fluorescence (480/564 nm) of Al³⁺ and alizarin red. Experimental parameters such as pH, concentration of the ligand, ionic strength of the solution, reaction time and temperature were optimized in order to maximize the analytical signal. Interferences of several ions (anions and cations) were studied and evaluated. The linear range of the method extends from 3 to 100 μg L⁻¹. Limit of detection (3s_b) was 0.9 μg L⁻¹. The method was tested with a silicate certified reference material. Interferences were eliminated by a liquid extraction with cupferron. Author for correspondence. E-mail: aucelior@rdc.puc-rio.br Received September 10, 2002; accepted January 15, 2003 Published online May 5, 2003     

Multifunctional polyesters as new candidate materials for biomedical applications. Synthesis and structural characterization

The present work was aimed at the development of functional polymeric materials to be used in the targeted delivery of proteic drug and tissue engineering fields. The adopted strategy was based on the design of special polymer classes whose structures and functionality could be easily modified by finely tuned synthetic procedures. Poly(ether ester)s containing H-bonding units were chosen as promising materials for the proposed applications. Commercially available precursors were successfully used for the synthesis of symmetrical diesters containing different H-bonding groups (amide, carbamate, and urea moieties). In all cases, pure products were obtained in good yields. Bulk polycondensation of the monomeric precursors with different mixtures of 1,4-butanediol and PEG 1000 diol afforded a variety of high molecular weight polymeric structures. Physical-chemical characterization of the polymers indicates that their thermal, mechanical, and swelling properties can be tailored by a proper selection of the H-bonding group and of the composition of the feed mixture.     

Conformational dynamics of a bispyridinium cyclophane

A complete study of the conformational behavior of 4,8-diaza-3(1,4),9(4,1)-dipyridina-1,6(1,4)-dibenzenacyclodecaphan-3(1),9(1)-bis(ilium) bishexafluorophosphate is described. This study allows us to conclude that the process observed by which the different chemical shifts of the pyridinium protons show coalescence at a high-temperature 1H NMR is the rotation around the C-N bond, whereas the conformational equilibrium between the four conformers is produced at low temperature.     

HOMO Stabilisation in π‐Extended Dibenzotetrathiafulvalene Derivatives for Their Application in Organic Field‐Effect Transistors

Three new organic semiconductors, in which either two methoxy units are directly linked to a dibenzotetrathiafulvalene (DB‐TTF) central core and a 2,1,3‐chalcogendiazole is fused on the one side, or four methoxy groups are linked to the DB‐TTF, have been synthesised as active materials for organic field‐effect transistors (OFETs). Their electrochemical behaviour, electronic absorption and fluorescence emission as well as photoinduced intramolecular charge transfer were studied. The electron‐withdrawing 2,1,3‐chalcogendiazole unit significantly affects the electronic properties of these semiconductors, lowering both the HOMO and LUMO energy levels and hence increasing the stability of the semiconducting material. The solution‐processed single‐crystal transistors exhibit high performance with a hole mobility up to 0.04 cm² V^?1 s^?1 as well as good ambient stability.