Priscilla L. Silva

Thermo-solvatochromism of zwitterionic probes in aqueous alcohols: effects of the properties of the probe and the alcohol

Thermo-solvatochromism of 2,6-dichloro-4-(2,4,6-triphenylpyridinium-1-yl)phenolate, 1-methylquinolinium-8-olate and 4-[2-(1-methylpyridinium-4-yl)ethenyl]phenolate, in the temperature range 10 to 60 °C (ethanol and 2-methoxyethanol) and 25 to 60 °C (2-methyl-2-propanol), has been investigated in binary water–alcohol mixtures. Thermo-solvatochromic data have been treated according to a recently introduced model that explicitly considers the presence of 1∶1 alcohol–water H-bonded species, ROH–W, in bulk solution, and its exchange equilibria with water and alcohol in the probe solvation micro-sphere. The composition of the latter is given in terms of the appropriate set of solvent fractionation factors. These indicate that all probes are more solvated by alcohol than by water. Additionally, solvation by ROH–W is favoured over solvation by either of the two precursor solvents. Comparison of the data of six alcohols (three from a recent study, methanol, 1-propanol and 2-propanol) showed that solvation by alcohols is affected more by probe–ROH hydrophobic interactions than by H-bonding to the probe phenoxy oxygen. Temperature increase results in a gradual desolvation of all probes, due to a decrease in the H-bonding of all components of the binary solvent mixture. The energy of the temperature-induced desolvation (10 to 60 °C) was found to range from 0.8 to 2.5 kcal mol−1.

Solvation in pure liquids: what can be learned from the use of pairs of indicators?

The solvation of six solvatochromic probes in a large number of solvents (33-68) was examined at 25 degrees C. The probes employed were the following: 2,6-diphenyl-4-(2,4,6-triphenylpyridinium-1-yl) phenolate (RB); 4-[(E)2-(1-methylpyridinium-4-yl)ethenyl] phenolate, MePM; 1-methylquinolinium-8-olate, QB; 2-bromo-4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl] phenolate, MePMBr, 2,6-dichloro-4-(2,4,6-triphenyl pyridinium-1-yl) phenolate (WB); and 2,6-dibromo-4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl] phenolate, MePMBr(2), respectively. Of these, MePMBr is a novel compound. They can be grouped in three pairs, each with similar pK(a) in water but with different molecular properties, for example, lipophilicity and dipole moment. These pairs are formed by RB and MePM; QB and MePMBr; WB and MePMBr(2), respectively. Theoretical calculations were carried out in order to calculate their physicochemical properties including bond lengths, dihedral angles, dipole moments, and wavelength of absorption of the intramolecular charge-transfer band in four solvents, water, methanol, acetone, and DMSO, respectively. The data calculated were in excellent agreement with available experimental data, for example, bond length and dihedral angles. This gives credence to the use of the calculated properties in explaining the solvatochromic behaviors observed. The dependence of an empirical solvent polarity scale E(T)(probe) in kcal/mol on the physicochemical properties of the solvent (acidity, basicity, and dipolarity/polarizability) and those of the probes (pK(a), and dipole moment) was analyzed by using known multiparameter solvation equations. For each pair of probes, values of E(T)(probe) (for example, E(T)(MePM) versus E(T)(RB)) were found to be linearly correlated with correlation coefficients, r, between 0.9548 and 0.9860. For the mercyanine series, the values of E(T)(probe) also correlated linearly, with (r) of 0.9772 (MePMBr versus MePM) and 0.9919 (MePMBr(2) versus MePM). The response of each pair of probes (of similar pK(a)) to solvent acidity is the same, provided that solute-solvent hydrogen-bonding is not seriously affected by steric crowding (as in case of RB). We show, for the first time, that the response to solvent dipolarity/polarizability is linearly correlated to the dipole moment of the probes. The successive introduction of bromine atoms in MePM (to give MePMBr, then MePMBr(2)) leads to the following linear decrease: pK(a) in water, length of the phenolate oxygen-carbon bond, length of the central ethylenic bond, susceptibility to solvent acidity, and susceptibility to solvent dipolarity/polarizability. Thus studying the solvation of probes whose molecular structures are varied systematically produces a wealth of information on the effect of solute structure on its solvation. The results of solvation of the present probes were employed in order to test the goodness of fit of two independent sets of solvent solvatochromic parameters.

Prolactin Promotes Breast Cancer Cell Migration through Actin Cytoskeleton Remodeling.

The role of prolactin on breast cancer development and progression is debated. Breast cancer progression largely depends on cell movement and on the ability to remodel the actin cytoskeleton. In this process, actin-binding proteins are requested to achieve fibrillar actin de-polymerization and relocation at the cell membrane. Kinases such as focal adhesion kinase (FAK) are later required to form actin/vinculin-enriched structures called focal adhesion complexes, which mediate firm adhesion to the extracellular matrix. These controllers are regulated by c-Src, which forms multiprotein signaling complexes with membrane receptors and is regulated by a number of hormones, including prolactin. We here show that breast cancer cells exposed to prolactin display an elevated c-Src expression and phosphorylation. In parallel, increased moesin and FAK expression and phosphorylation are found. These molecular changes are associated to relocation to the plasma membrane of cytoskeletal actin fibers and to increased horizontal cell movement. In conclusion, prolactin regulates actin remodeling and enhances breast cancer cell movement. This finding broadens the understanding of prolactin actions on breast cancer cells, highlighting new pathways that may be relevant to on breast cancer progression.

Effects of hyperprolactinemia on the tibial epiphyseal plate of mice treated with sex hormones

Abstract The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the tibial epiphyseal plate of hormone-treated oophorectomized mice. For this purpose, 18 animals with intact ovaries were allocated to two groups, M (metoclopramide) and V (vehicle). One hundred and eight oophorectomized animals were allocated to 12 subgroups: Oophx/V (vehicle); Ooph/M (metoclopramide); Oophx/V + E (vehicle + estradiol); Oophx/M + E (metoclopramide + estradiol); Oophx/V + P (vehicle + progesterone); Oophx/M + P (metoclopramide + progesterone); Oophx/V + T (vehicle + testosterone); Oophx/M + T (metoclopramide + testosterone); Oophx/V + E + P (Vehicle + estradiol + progesterone); Oophx/M + E + P (metoclopramide + estradiol + progesterone); Oophx/V + E + P + T (vehicle + estradiol + progesterone + testosterone); Oophx/M + E + P + T (metoclopramide + estradiol + progesterone + testosterone). After a 50-day treatment was performed histomorphometric and immunohistochemical cell death analysis. In the epiphyseal plate of the hyperprolactinemic and/or oophorectomized animals, cell proliferation and bone formation decreased, inducing intensified cell death. In the sex steroid-treated animals, estrogen boosted cell proliferation; progesterone, bone formation and testosterone, both cell proliferation and bone formation. These findings suggest that oophorectomy and hyperprolactinemia changed epiphyseal plate morphology causing cartilage degeneration. Treatment with combined sex steroids may diminish such deleterious effects.