Consequences of thimerosal on human erythrocyte hemoglobin: Assessing functional and structural protein changes induced by an organic mercury compound.

BACKGROUND: Thimerosal (TM) is an organic mercury compound used as a preservative in many pharmacological inputs. Mercury toxicity is related to structural and functional changes in macromolecules such as hemoglobin (Hb) in erythrocytes (Ery). METHOD: Human Hb and Ery were used to evaluate O2 uptake based on the TM concentration, incubation time, and temperature. The influence of TM on the sulfhydryl content, production of reactive oxygen species (ROS), and membrane fragility was also evaluated. Raman spectra and atomic force microscopy (AFM) profiles for Ery in the presence and absence of TM were calculated, and docking studies were performed. RESULTS: At 37 °C, with 2.50 µM TM (higher concentration) and after 5 min of incubation in Hb and Ery, we observed a reduction in O2 uptake of up to 50 %, while HgCl2, which was used as a positive control, showed a reduction of at least 62 %. Total thiol assays in the presence of NEM (thiol blocker) quantified the preservation of almost 60 % of free SH in Ery. Based on the Raman spectrum profile from Ery-TM, structural differences in the porphyrinic ring and the membrane lipid content were confirmed. Finally, studies using AFM showed changes in the morphology and biomechanical properties of Ery. Theoretical studies confirmed these experimental results and showed that the cysteine (Cys) residues present in Hb are involved in the binding of TM. CONCLUSION: Our results show that TM binds to human Hb via free Cys residues, causing conformation changes and leading to harmful effects associated with O2 transport.

Are the Absorption Spectra of Doxorubicin Properly Described by Considering Different Tautomers?

The elucidation of the action of doxorubicin (DOX) has been considered a challenge for cancer therapy. Using theoretical approaches, we investigated the structure and electronic properties of DOX as a function of pH, which we thought likely to be related to the influence of its tautomers. Regarding the relative stabilities among the tautomers, the results obtained from PM6 were the most similar to those obtained from DFT. The theoretical absorption spectrum for each tautomeric species simply showed a single absorption peak located around 400 nm, in contrast to the experimental absorption spectra in the literature that showed four absorption bands. The experimental evidence was properly explained by considering four tautomeric conformers of DOX. The spectroscopic study of the deprotonated tautomers also suggested the presence of four deprotonated tautomers at more basic pH values. The spectrum at pH 10.08 can be explained by the presence of protonated and deprotonated doxorubicin species.

Semiempirical quantum chemistry model for the lanthanides: RM1 (Recife Model 1) parameters for dysprosium, holmium and erbium.

Complexes of dysprosium, holmium, and erbium find many applications as single-molecule magnets, as contrast agents for magnetic resonance imaging, as anti-cancer agents, in optical telecommunications, etc. Therefore, the development of tools that can be proven helpful to complex design is presently an active area of research. In this article, we advance a major improvement to the semiempirical description of lanthanide complexes: the Recife Model 1, RM1, model for the lanthanides, parameterized for the trications of Dy, Ho, and Er. By representing such lanthanide in the RM1 calculation as a three-electron atom with a set of 5 d, 6 s, and 6 p semiempirical orbitals, the accuracy of the previous sparkle models, mainly concentrated on lanthanide-oxygen and lanthanide-nitrogen distances, is extended to other types of bonds in the trication complexes' coordination polyhedra, such as lanthanide-carbon, lanthanide-chlorine, etc. This is even more important as, for example, lanthanide-carbon atom distances in the coordination polyhedra of the complexes comprise about 30% of all distances for all complexes of Dy, Ho, and Er considered. Our results indicate that the average unsigned mean error for the lanthanide-carbon distances dropped from an average of 0.30 Å, for the sparkle models, to 0.04 Å for the RM1 model for the lanthanides; for a total of 509 such distances for the set of all Dy, Ho, and Er complexes considered. A similar behavior took place for the other distances as well, such as lanthanide-chlorine, lanthanide-bromine, lanthanide, phosphorus and lanthanide-sulfur. Thus, the RM1 model for the lanthanides, being advanced in this article, broadens the range of application of semiempirical models to lanthanide complexes by including comprehensively many other types of bonds not adequately described by the previous models.

Water-soluble Tb3+ and Eu3+ complexes with ionophilic (ionically tagged) ligands as fluorescence imaging probes.

This article describes a straightforward and simple synthesis of ionically tagged water-soluble Eu(3+) and Tb(3+) complexes (with ionophilic ligands) applied for bioimaging of invasive mammal cancer cells (MDA-MB-231). Use of the task-specific ionic liquid 1-methyl-3-carboxymethyl-imidazolium chloride (MAI·Cl) as the ionophilic ligand (ionically tagged) proved to be a simple, elegant, and efficient strategy to obtain highly fluorescent water-soluble Eu(3+) (EuMAI) and Tb(3+) (TbMAI) complexes. TbMAI showed an intense bright green fluorescence emission selectively staining endoplasmic reticulum of MDA-MB-231 cells.