Focus on the Use of Resveratrol in Bladder Cancer.

Bladder cancer is the most common tumor of the urinary system, with a high incidence in the male population. Surgery and intravesical instillations can eradicate it, although recurrences are very common, with possible progression. For this reason, adjuvant therapy should be considered in all patients. Resveratrol displays a biphasic dose response both in vitro and in vivo (intravesical application) with an antiproliferative effect at high concentrations and antiangiogenic action in vivo (intraperitoneal application) at a low concentration, suggesting a potential role for it in clinical management as an adjuvant to conventional therapy. In this review, we examine the standard therapeutical approach to bladder cancer and the preclinical studies that have investigated resveratrol in xenotransplantation models of bladder cancer. Molecular signals are also discussed, with a particular focus on the STAT3 pathway and angiogenic growth factor modulation.

Photodissociation Dynamics of CO-Forming Channels on the Ground-State Surface of Methyl Formate at 248 nm: Direct Dynamics Study and Assessment of Generalized Multicenter Impulsive Models.

The photodissociation dynamics of methyl formate in the electronic ground state S0, initiated by a 248 nm-wavelength laser, is studied by direct dynamics simulations. We analyze five channels, where four of them have as products CH3OH + CO, one leading to the formation of three fragments, H2CO + H2 + CO, and a channel characterized by a roaming transition state. The analysis of energy distribution among the degrees of freedom of the product and the comparison with experimental results previously published by other groups provide the ingredients to distinguish the examined dissociation pathways. The interpretation of the results proves that the characterization of dissociation mechanisms must rely on a dynamics approach involving multiple electronic states, including considerations on the features of the S1/S0 conical intersection. Here, we also assess the generalized multicenter impulsive model, GMCIM, that has been designed for dissociation processes with exit barriers, and the energy distribution in the products is predicted on the basis of information from the saddle points and the intrinsic reaction coordinates. Main features, advantages, limits, and future perspectives of the method are reported and discussed.

Molecular beam scattering experiments on noble gas-propylene oxide: Total integral cross sections and potential energy surfaces of He- and Ne-C3H6O.

The interactions of He and Ne with propylene oxide have been investigated with the molecular beam technique by measuring the total (elastic + inelastic) integral cross section as a function of collision velocity. Starting from the analysis of these experimental data, potential energy surfaces, formulated as a function of the separation distance and orientation of propylene oxide with respect to the interacting partners, have been built: The average depth of potential wells (located at intermediate separation distances) has been characterized by analyzing the observed "glory" quantum effects, and the strength of long-range attractions has been obtained from the magnitude and the velocity dependence of the smooth component of measured cross sections. The surfaces, tested and improved against new ab initio calculations of minima interaction energies at the complete basis set level of theory, are defined in the full space of relative configurations. This represents a crucial condition to provide force fields useful to carry out, in general, important molecular property simulations and to evaluate, in the present case, the spectroscopic features and the dynamical selectivity of weakly bound complexes formed by propylene oxide, a prototype chiral species, during collisions in interstellar clouds and winds, in the space and planetary atmospheres. The adopted formulation of the interaction can be readily extended to similar systems, involving heavier noble gases or diatomic molecules (H2, O2, and N2) as well as to propylene oxide dimers.

UV Photodissociation of Halothane in a Focused Molecular Beam: Space-Speed Slice Imaging of Competitive Bond Breaking into Spin-Orbit-Selected Chlorine and Bromine Atoms.

A molecular beam of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) is focused by a hexapolar electrostatic field and photolyzed by UV laser radiation at 234 nm. Angular and speed distributions of chlorine and bromine photofragments emitted from halothane are measured for both spin-orbit states independently. Although the dissociation energy of the C-Cl bond is larger than that of C-Br, the relative yield of Cl to Br was found to be approximately 2. Measured speed and angular distributions of atomic fragments show distinct kinetic energy release and scattering characteristics: for bromine, observed fast and aligned fragments exhibit a signature of a direct mode of dissociation for the C-Br bond, via the electronically excited potential energy surface denoted nσ*(C-Br), of repulsive nature; for chlorine, a variation in the features is observed for the dissociation pathway through nσ*(C-Cl), from a modality similar to the bromine case, leading to fragments with appreciable kinetic energy release and pronounced directionality, to a modality involving slow products, nearly isotopically distributed. The origin of this behavior can be attributed to nonadiabatic interaction operating between the nσ*(C-Br) and nσ*(C-Cl) surfaces. These results are not only relevant for a detailed understanding of adiabatic versus diabatic coupling mechanisms in the manifold of excited states populated by photon absorption, but they also point out the possibility of selectively inducing specific dissociation pathways, even when involving energetically unfavorable outcomes, such as, in this case, the prevailing rupture of the stronger C-Cl bond against that of the weaker C-Br bond.

Vectorial imaging of the photodissociation of 2-bromobutane oriented via hexapolar state selection.

Molecular orientation techniques are becoming available in the study of elementary chemical processes, in order to highlight those structural and dynamical properties that would be concealed by random rotational motions. Recently successful orientation was achieved for asymmetric-top and chiral molecules of much larger complexity than hitherto. In this work, we report and discuss the correlation between the vectors' photofragment recoil velocity v, transition dipole moment µ, and permanent dipole moment d in a dissociation experiment on hexapole oriented 2-bromobutane, photoinitiated by a linearly polarized laser. The sliced ion images of the Br*(2P1/2) and Br(2P3/2) photofragments were acquired at 234.0 and 254.1 nm, respectively, by a (2 + 1) resonance-enhanced multiphoton ionization technique. A detailed analysis of the sliced ion images obtained at a tilting angle 45° of laser polarization provides information on the correlation of the three vectors, which are confined by two polar angles α and χ and one azimuthal angle φµd in the recoil frame. The sliced ion images of Br fragments eliminated individually from the enantiomers at 254.1 nm yield an asymmetric factor close to zero; for this reason the photofragment angular distributions do not show significant differences. The elimination of the Br* fragment at 234.0 nm is mainly correlated with a parallel transition, giving rise to a large anisotropy parameter of 1.85, and thus can be considered as a single state excitation. The resulting recoil frame angles are optimized to 163° ± 8° and 164° ± 1° for α and χ, respectively, whereas φµd is approaching 0° for the best fit. Since for the present molecule, the three vectors have an only slight spatial arrangement, the photofragment angular distributions of the two enantiomers do not show appreciable differences. Theoretical and computational simulations provide us the basis to state that oriented enantiomers can be discriminated on-the-fly in photodissociation processes even initiated by non-circularly polarized light, provided that the three vectors encountered above have specific three-dimensional arrangements. The fact that Br fragment elimination involves a multi-potential dissociation carries uncertainties in theoretical estimates of the vector direction. Therefore, this work represents a preliminary but significant step on the road to chiral discrimination on-the-fly, which is shown to be best propitiated in molecules where vectors are far from having degenerate mutual angular directions.

Stereodynamic Imaging of Bromine Atomic Photofragments Eliminated from 1-Bromo-2-methylbutane Oriented via Hexapole State Selector.

Both single-laser and two-laser experiments were conducted to look into the ion-imaging of Br*(2P1/2) and Br(2P3/2) photofragmented from 1-bromo-2-methylbutane in the range 232-240 nm via a detection scheme of (2+1) resonance-enhanced multiphoton ionization. The angular analysis of these photofragment distributions yields the anisotropy parameter ß = 1.88 ± 0.06 for the Br* excited state which arises from a parallel transition, while ß = 0.63 ± 0.09 for the Br ground state indicates the contribution from both a perpendicular transition and a non-adiabatic transition. When a hexapole coupled with an orienting field was implemented, the parent molecules are spatially oriented to yield an orientation efficiency |⟨cos Î¸⟩| of 0.15. Besides the χ angle between the recoil velocity v and the transition dipole moment µ, orienting molecules allows for the evaluation of the angle α between v and the permanent molecular dipole moment d. The angular analysis of Br* photofragment distribution yields χ = 11.5° and α in the range from 160° to 180° with weak dependency. In the two-laser experiments, the angular anisotropy of Br photofragment distribution was found to be smaller (0.38 ± 0.10) when the photolysis wavelength was red-shifted to 240 nm, suggesting the increasing contributions from perpendicular transitions.

"Transitivity": A Code for Computing Kinetic and Related Parameters in Chemical Transformations and Transport Phenomena.

The Transitivity function, defined in terms of the reciprocal of the apparent activation energy, measures the propensity for a reaction to proceed and can provide a tool for implementing phenomenological kinetic models. Applications to systems which deviate from the Arrhenius law at low temperature encouraged the development of a user-friendly graphical interface for estimating the kinetic and thermodynamic parameters of physical and chemical processes. Here, we document the Transitivity code, written in Python, a free open-source code compatible with Windows, Linux and macOS platforms. Procedures are made available to evaluate the phenomenology of the temperature dependence of rate constants for processes from the Arrhenius and Transitivity plots. Reaction rate constants can be calculated by the traditional Transition-State Theory using a set of one-dimensional tunneling corrections (Bell (1935), Bell (1958), Skodje and Truhlar and, in particular, the deformed ( d -TST) approach). To account for the solvent effect on reaction rate constant, implementation is given of the Kramers and of Collins-Kimball formulations. An input file generator is provided to run various molecular dynamics approaches in CPMD code. Examples are worked out and made available for testing. The novelty of this code is its general scope and particular exploit of d -formulations to cope with non-Arrhenius behavior at low temperatures, a topic which is the focus of recent intense investigations. We expect that this code serves as a quick and practical tool for data documentation from electronic structure calculations: It presents a very intuitive graphical interface which we believe to provide an excellent working tool for researchers and as courseware to teach statistical thermodynamics, thermochemistry, kinetics, and related areas.

Transient isomers in the photodissociation of bromoiodomethane.

The photochemistry of halomethanes is fascinating for the complex cascade reactions toward either the parent or newly synthesized molecules. Here, we address the structural rearrangement of photodissociated CH2IBr in methanol and cyclohexane, probed by time-resolved X-ray scattering in liquid solution. Upon selective laser cleavage of the C-I bond, we follow the reaction cascade of the two geminate geometrical isomers, CH2I-Br and CH2Br-I. Both meta-stable isomers decay on different time scales, mediated by solvent interaction, toward the original parent molecule. We observe the internal rearrangement of CH2Br-I to CH2I-Br in cyclohexane by extending the time window up to 3 µs. We track the photoproduct kinetics of CH2Br-I in methanol solution where only one isomer is observed. The effect of the polarity of solvent on the geminate recombination pathways is discussed.

Double photoionization of propylene oxide: A coincidence study of the ejection of a pair of valence-shell electrons.

Propylene oxide, a favorite target of experimental and theoretical studies of circular dichroism, was recently discovered in interstellar space, further amplifying the attention to its role in the current debate on protobiological homochirality. In the present work, a photoelectron-photoion-photoion coincidence technique, using an ion-imaging detector and tunable synchrotron radiation in the 18.0-37.0 eV energy range, permits us (i) to observe six double ionization fragmentation channels, their relative yields being accounted for about two-thirds by the couple (C2H4+, CH2O+) and one-fifth by (C2H3+, CH3O+); (ii) to measure thresholds for their openings as a function of photon energy; and (iii) to unravel a pronounced bimodality for a kinetic-energy-released distribution, fingerprint of competitive non-adiabatic mechanisms.

Stereodirectional images of molecules oriented by a variable-voltage hexapolar field: Fragmentation channels of 2-bromobutane electronically excited at two photolysis wavelengths.

The asymmetric-top molecule 2-bromobutane is oriented by means of a hexapole state selector; the angular distribution of the bromine atom photofragment, for the two fine-structure components, is acquired by velocity-map ion imaging. The molecular beam, spatially oriented along the time-of-flight axis, is intersected with a linearly polarized laser, whose polarization is tilted by 45° with respect to the detector surface. To obtain the mixing ratio of the perpendicular and parallel transitions, the fragment ion images and angular distributions can be appropriately simulated to give insight on the population mechanism of the specific electronic state involved at each selected excitation wavelength. The photofragment images obtained at 238.6 nm yielded an asymmetry factor ß1 of 0.67, indicative of the extent of molecular orientation, and an anisotropy parameter ß2 of 1.03, which is a signature of a prevailing parallel transition along the C-Br axis. When the photolysis wavelength is tuned to 254.1 nm, the corresponding angular distribution is less asymmetric (ß1 = 0.24) and the obtained small value ß2 = 0.12 is a characteristic of a predominantly perpendicular transition. The photofragment angular distributions are also affected by hexapole voltage, especially regarding the asymmetry factor, and this aspect provides information on the effect of molecular orientation.

Rovibrationally Excited Molecules on the Verge of a Triple Breakdown: Molecular and Roaming Mechanisms in the Photodecomposition of Methyl Formate.

For the photodissociation of the simplest of esters, methyl formate HCOOCH3, the energy threshold for triple fragmentation into H, CH3O, and CO was measured by previous ion-imaging experiments at a sequence of wavelengths. The translational energy features of product CO in the ground vibrational level (υ = 0) and for selected rotational states were characterized. In this integrated experimental and theoretical approach (i) the focus is at a laser energy barely below that threshold; (ii) Fourier-transform infrared emission spectroscopy measurements probe the rovibrational energy deposition in CO(υ) for υ > 0 and the emergence of the roaming phenomenon; (iii) accompanying quantum chemical calculations describe the selective rupture of bonds; and (iv) molecular dynamics simulations of dissociation are performed, introducing an approach explicitly involving outcomes from paths originated nonadiabatically through conical intersections. Quantitative information on energy disposal is provided: we found extensive vibrational excitation of CO, while rotational bands are colder and bimodal, due to contributions from direct and roaming modes.

Interactions of Hydrogen Molecules with Halogen-Containing Diatomics from Ab Initio Calculations: Spherical-Harmonics Representation and Characterization of the Intermolecular Potentials.

For the prototypical diatomic-molecule-diatomic-molecule interactions H2-HX and H2-X2, where X = F, Cl, Br, quantum-chemical ab initio calculations are carried out on grids of the configuration space, which permit a spherical-harmonics representation of the potential energy surfaces (PESs). Dimer geometries are considered for sets of representative leading configurations, and the PESs are analyzed in terms of isotropic and anisotropic contributions. The leading configurations are individuated by selecting a minimal set of mutual orientations of molecules needed to build the spherical-harmonic expansion on geometrical and symmetry grounds. The terms of the PESs corresponding to repulsive and bonding dimer geometries and the averaged isotropic term, for each pair of interacting molecules, are compared with representations in terms of a potential function proposed by Pirani et al. (see Chem. Phys. Lett. 2004, 394, 37-44 and references therein). Connections of the involved parameters with molecular properties provide insight into the nature of the interactions.

Hexapole-Oriented Asymmetric-Top Molecules and Their Stereodirectional Photodissociation Dynamics.

Molecular orientation is a fundamental requisite in the study of stereodirected dynamics of collisional and photoinitiated processes. In this past decade, variable hexapolar electric filters have been developed and employed for the rotational-state selection and the alignment of molecules of increasing complexity, for which the main difficulties are their mass, their low symmetry, and the very dense rotational manifold. In this work, for the first time, a complex molecule such as 2-bromobutane, an asymmetric top containing a heavy atom (the bromine), was successfully oriented by a weak homogeneous field placed downstream from the hexapolar filter. Efficiency of the orientation was characterized experimentally, by combining time-of-flight measurements and a slice-ion-imaging detection technique. The application is described to the photodissociation dynamics of the oriented 2-bromobutane, which was carried out at a laser wavelength of 234 nm, corresponding to the breaking of the C-Br bond. The Br photofragment is produced in both the ground Br ((2)P3/2) and the excited Br ((2)P1/2) electronic states, and both channels are studied by the slice imaging technique, revealing new features in the velocity and angular distributions with respect to previous investigations on nonoriented molecules.

Roads leading to roam. Role of triple fragmentation and of conical intersections in photochemical reactions: experiments and theory on methyl formate.

The exploration of alternative roads that open to molecules with sufficient energy to yield different products permits prediction and eventually control of the outcomes of chemical reactions. Advanced imaging techniques for monitoring laser-induced photodissociation are here combined with dynamical simulations, involving ample sets of classical trajectories generated on a quantum chemical potential energy surface. Methyl formate, HCOOCH3, is photodissociated at energies near the triple fragmentation threshold into H, CO and OCH3. Images of velocity and rotational distributions of CO exhibit signatures of alternative routes, such as those recently designated as transition-state vs. roaming-mediated. Furthermore, a demonstration of the triple fragmentation route is given, and also confirmed by H-atom product imaging and FTIR time-resolved spectra of the intermediate HCO radical. In addition, the relevance of nonadiabatic transitions promoted by a conical intersection is clarified by simulations as the privileged "reactivity funnel" of organic photochemistry, whereby the outcomes of molecular photoexcitation are delivered to electronic ground states.

Control of conformers combining cooling by supersonic expansion of seeded molecular beams with hexapole selection and alignment: experiment and theory on 2-butanol.

Selection and alignment of rotamers and, more in general, of conformers in the gas phase is a challenge that we tackle experimentally by supersonic expansion of seeded molecular beams and hexapolar electrostatic fields with quadrupole mass detection. The studied system involves the nine conformers of the asymmetric-top molecule 2-butanol, which coexist because of nearly free rotations around a CC and a CO bond. From the measured time-of-flight of a 2-butanol supersonic molecular beam seeded in either He or Ar, the corresponding velocity distributions are obtained. The different nature and masses of the seeding gas decrease selectively the vibrational temperature and determine the population of the conformers, which is assessed on the basis of their statistical distribution, derived from high level accompanying quantum mechanical calculations. The use of a hexapolar electrostatic field permits us to induce a variation of the population distribution as a function of the applied voltage and of the selective focusing and alignment of the conformers. A technique, recently developed for treating asymmetric tops and involving extensive trajectory simulations, is applied to obtain the link between the focusing curves, i.e. the dependence of the beam intensity on the hexapole voltage, and the conformers' populations and alignment. Perspectives are provided for photo- and stereo-dynamics experiments, particularly appealing also on account that 2-butanol is the simplest chiral alcohol.

Directions of chemical change: experimental characterization of the stereodynamics of photodissociation and reactive processes.

This perspective article aims at accounting for the versatility of some current experimental investigations for exploring novel paths in chemical reactions. It updates a previous one [Phys. Chem. Chem. Phys., 2005, 5, 291] and is limited to work by the authors. The use of advanced molecular beam techniques together with a combination of modern tools for specific preparation, selection and detection permits us to discover new trends in reactivity in the gas phase as well as at interfaces. We specifically discuss new facets of stereodynamics, namely the effects of molecular orientation and alignment on reactive and photodissociation processes. Further topics involve roaming paths and triple fragmentation in photodissociation probed by imaging techniques, chirality effects in collisions and deviations from Arrhenius behavior in the temperature dependence of chemical reactions.

Synthesis and Characterization of ZIF-90 Nanoparticles as Potential Brain Cancer Therapy.

Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood-brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system.

Cranberry/Chondroitin Sulfate Co-precipitate as a New Method for Controlling Urinary Tract Infections.

Urinary tract infections (UTI), which are among the most frequent cases of infectious diseases, mainly affect women. The most common treatment approach involves the use of antibiotics, although this solution is not always the most suitable, mainly because of the resistance that bacterial strains develop. Proanthocyanidins are a class of polyphenols, abundantly contained in cranberry extracts, which have shown beneficial effects in the treatment of urinary tract infections, due to their anti-adhesive properties toward bacteria, with respect to the membranes of the cells of the urothelium and intestine, thus reducing their virulence. In this work, we demonstrate via microscopy and scattering measurements how a mixture of cranberry and chondroitin sulfate can form a crosslinked structure with barrier properties. By using a design of experiment (DOE), we optimized the mass ratio to obtain a precipitate between cranberry extract and chondroitin sulfate in the presence of N-acetylcysteine and hyaluronic acid. By using transepithelial electrical resistance (TEER) chambers, we confirmed the barrier properties of the best mixture obtained with the DOE. Lastly, the antibiofilm action was investigated against five strains of Escherichia coli with different antibiotic sensitivity. The precipitate displayed a variable inhibitory effect in biofilm formation with major effects in UTI with an antibiotic resistance profile.

LY294002 Inhibits Intermediate Conductance Calcium-Activated Potassium (KCa3.1) Current in Human Glioblastoma Cells.

Glioblastomas (GBs) are among the most common tumors with high malignancy and invasiveness of the central nervous system. Several alterations in protein kinase and ion channel activity are involved to maintain the malignancy. Among them, phosphatidylinositol 3-kinase (PI3K) activity and intermediate conductance calcium-activated potassium (KCa3.1) current are involved in several aspects of GB biology. By using the electrophysiological approach and noise analysis, we observed that KCa3.1 channel activity is LY294002-sensitive and Wortmannin-resistant in accordance with the involvement of PI3K class IIß (PI3KC2ß). This modulation was observed also during the endogenous activation of KCa3.1 current with histamine. The principal action of PI3KC2ß regulation was the reduction of open probability in intracellular free calcium saturating concentration. An explanation based on the "three-gate" model of the KCa3.1 channel by PI3KC2ß was proposed. Based on the roles of KCa3.1 and PI3KC2ß in GB biology, a therapeutic implication was suggested to prevent chemo- and radioresistance mechanisms.

Quantum chemistry of C(3)H(6)O molecules: structure and stability, isomerization pathways, and chirality changing mechanisms.

Electronic structure calculations were carried out to study the various isomers of formula C(3)H(6)O, as a part of our current quantum chemical and dynamical approaches to intra- and intermolecular kinetics for the C(n)H(2n)O (n = 1, 2, 3) molecules. The usefulness of the GRRM (global reaction route mapping) program developed by Ohno and Maeda in predicting the structure of all isomers and of the transition states connecting them is fully exploited. All the isomers are identified as local minima on the MP2/CC-PVDZ potential energy surface. Acetone is the most stable isomer. In increasing order of stability the others are propanal, 2-propenol, 1-propenol, allyl alcohol, methyl vinyl ether, cyclopropanol, propylene oxide, and oxetane. Various isomerization paths connecting them are identified. All the transition states are fully characterized using intrinsic reaction coordinate calculations. The isomerization reactions may proceed through a single step or involve an intermediate species which is either a carbene or a diradical. Special attention is devoted to propylene oxide, a favorite molecule in current photochemical and stereodynamical studies because of its chiral nature. It is a rigid molecule, and chirality switching is found to be supported by its isomers. Two different chirality switching mechanisms which are assisted by propanal and allyl alcohol are presented.