Binding of chemicals to melanins re-examined: adsorption of some drugs to the surface of melanin particles.

This work presents a first attempt to study the interaction of some drugs with melanins, realistically considered as solid aggregates of primary particles. This situation appears similar to the adsorption of organic molecules onto the surface of colloidal absorbers, as active carbon, zeolites or titanium dioxide. We have applied some of the most popular theoretical models used in technological applications with the aim to give a more realistic picture of the melanin-drug interaction responsible for some observed side effects in vivo. Moreover, this approach can simplify the problem of the search of the physical parameters dominating the binding processes, by reducing the phenomenon to a simple physisorption/chemisorption, at least in a first approximation. We have studied the binding to melanin of gentamicin, methotrexate and chlorpromazine, molecules with different physico-chemical and structural characteristics. Our study demonstrates the possibility to fit experimental adsorption data with Langmuir, Freundlich, Tempkin and Dubinin-Radushkevich equations. In such a way we obtain binding parameters useful to characterize the drug-surface interaction in terms of energy and of mean affinity.

Population exposure to hazardous air quality due to the 2015 fires in Equatorial Asia.

Vegetation and peatland fires cause poor air quality and thousands of premature deaths across densely populated regions in Equatorial Asia. Strong El-Niño and positive Indian Ocean Dipole conditions are associated with an increase in the frequency and intensity of wildfires in Indonesia and Borneo, enhancing population exposure to hazardous concentrations of smoke and air pollutants. Here we investigate the impact on air quality and population exposure of wildfires in Equatorial Asia during Fall 2015, which were the largest over the past two decades. We performed high-resolution simulations using the Weather Research and Forecasting model with Chemistry based on a new fire emission product. The model captures the spatio-temporal variability of extreme pollution episodes relative to space- and ground-based observations and allows for identification of pollution sources and transport over Equatorial Asia. We calculate that high particulate matter concentrations from fires during Fall 2015 were responsible for persistent exposure of 69 million people to unhealthy air quality conditions. Short-term exposure to this pollution may have caused 11,880 (6,153-17,270) excess mortalities. Results from this research provide decision-relevant information to policy makers regarding the impact of land use changes and human driven deforestation on fire frequency and population exposure to degraded air quality.

Using satellite-based measurements to explore spatiotemporal scales and variability of drivers of new particle formation.

New particle formation (NPF) can potentially alter regional climate by increasing aerosol particle (hereafter particle) number concentrations and ultimately cloud condensation nuclei. The large scales on which NPF is manifest indicate potential to use satellite-based (inherently spatially averaged) measurements of atmospheric conditions to diagnose the occurrence of NPF and NPF characteristics. We demonstrate the potential for using satellite-based measurements of insolation (UV), trace gas concentrations (sulfur dioxide (SO2), nitrogen dioxide (NO2), ammonia (NH3), formaldehyde (HCHO), and ozone (O3)), aerosol optical properties (aerosol optical depth (AOD) and Ångström exponent (AE)), and a proxy of biogenic volatile organic compound emissions (leaf area index (LAI) and temperature (T)) as predictors for NPF characteristics: formation rates, growth rates, survival probabilities, and ultrafine particle (UFP) concentrations at five locations across North America. NPF at all sites is most frequent in spring, exhibits a one-day autocorrelation, and is associated with low condensational sink (AOD × AE) and HCHO concentrations, and high UV. However, there are important site-to-site variations in NPF frequency and characteristics, and in which of the predictor variables (particularly gas concentrations) significantly contribute to the explanatory power of regression models built to predict those characteristics. This finding may provide a partial explanation for the reported spatial variability in skill of simple generalized nucleation schemes in reproducing observed NPF. In contrast to more simple proxies developed in prior studies (e.g., based on AOD, AE, SO2, and UV), use of additional predictors (NO2, NH3, HCHO, LAI, T, and O3) increases the explained temporal variance of UFP concentrations at all sites.

A band model for melanin deducted from optical absorption and photoconductivity experiments.

Natural and synthetic melanins have been studied by optical absorption and photoconductivity measurements in the range 200--700 nm. Both optical absorption and photoconductivity increase in the ultraviolet region, and a negative photoconductivity was observed with a maximum near 500 nm. This behaviour has been interpreted by the band model of amorphous materials and an "optical gap" of 3.4 eV has been determined.

Magnetic investigations of human mesencephalic neuromelanin.

Pigmentation of neurons in substantia nigra is due to neuromelanin, a pigment that stores large amounts of iron. Human mesencephalic neuromelanin has been investigated by means of magnetic susceptibility measurements as a function of temperature. Magnetic measurements provide a physico-chemical characterization of the iron cluster buried in the organic melanin matrix and support the view that iron is not simply chelated, but rather is organized in a three-dimensional network. The paramagnetism of isolated iron ions is observed, in agreement with electron paramagnetic resonance spectroscopy. Furthermore, antiferromagnetic grains with a large size distribution function are present. These grains contain N spins coupled antiferromagnetically; however, N(1/2) spins are decoupled from the grain bulk and parallelly aligned. The latter subgrains are superparamagnetic with a blocking temperature ranging between 5 K and room temperature. This behavior has not been observed in synthetic melanin, where the paramagnetic contribution is strongly enhanced. Preliminary results on pigment isolated from patients affected by Parkinson's disease, a neurodegenerative pathology involving primarily pigmented neurons in substantia nigra pars compacta, show a lower total magnetization compared to control neuromelanin. The temperature behavior of zero field cooling and field cooling magnetizations is similar for both. The significant depletion of iron content in Parkinson's disease neuromelanin could indicate a progressive Fe migration from its storage environment to the cytosol.

The interaction of melanin with 8-methoxypsoralen: effect on radiative and nonradiative transitions. A fluorescence and pulsed photoacoustic study.

The interaction of 8-methoxypsoralen (8-MOP) with synthetic eumelanin was investigated using static and time-resolved fluorescence and pulsed photoacoustic calorimetry. Due to the strong overlap of the absorption bands of melanin and 8-MOP, a method is presented to account for the systematic errors introduced by the optical filter effect exerted by each absorbing species in the fluorescence and the photoacoustic measurements. As a preliminary step to the understanding of the nonradiative behavior of the psoralen-melanin complexes, the photoacoustic parameters of 8-MOP in various solvents were determined. Spectroscopic data indicate the absence of interaction at the ground-state level, whereas the singlet excited state of 8-MOP is quenched by the pigment; the average fluorescence lifetimes are independent of the melanin concentration, thus indicating a static quenching mechanism. The photoacoustic data show that the quenching process involves an increased intersystem crossing probability, which is almost unaffected by the presence of oxygen, as expected for a molecule essentially acting as a type I photosensitizing agent.

On the approximation of stochastic processes by approximate identity neural networks.

The ability of a neural network to learn from experience can be viewed as closely related to its approximating properties. By assuming that environment is essentially stochastic it follows that neural networks should be able to approximate stochastic processes. The aim of this paper is to show that some classes of artificial neural networks exist such that they are capable of providing the approximation, in the mean square sense, of prescribed stochastic processes with arbitrary accuracy. The networks so defined constitute a new model for neural processing and extend previous results concerning approximating capabilities of artificial neural networks.

Effect of U.V. irradiation and of various chemical conditions on the oxidation of NADH by pheomelanins.

The oxidation reaction of NADH with synthetic and natural pheomelanins was studied under various physicochemical conditions in order to obtain information about the molecular steps involved in the electron transfer process. The comparison with the previous data on eumelanins suggests that the reaction pathways are the same and that the greater photosensitivity of pheomelanins, observed in other experiments, is manifested in the redox reactions with NADH as an increased formation of quinone groups and of superoxide anions.

Involvement of superoxide ions in the oxidation of NADH by melanins.

The reactions of oxidation of NADH by Dopa and Dopamine-melanins show inhibition with low quantities of Superoxide dismutase, the enzyme which catalyzes the reaction: O2- + O2- + 2H+ leads to H2O2 + O2 and which has been used as an indicator of the involvement of superoxide ions in many biochemical systems. The reaction was also investigated in the presence of metal ions (Cu2, Zn2+ and Co2+) that are able to increase the extent of oxidation, and also in this case the inhibition effect of superoxide dismutase was observed. The results are interpreted in terms of a single electron pathway involving the superoxide ion and NAD.

Fluorescence depolarization studies of melanosomal membranes from different sources.

In the present paper we report a comparative study of physical properties and biochemical composition of isolated melanosomal membranes extracted from bovine eyes and from an equine spleen melanoma. Some biophysical characteristics of such membranes were obtained by steady-state and time resolved fluorescence spectroscopy using DPH as fluorescent probe. By these methods we have measured both static fluorescence polarization and fluorescence lifetimes and from the experimental data we have calculated the rotational correlation times by Perrin's equation. Since dynamic and static parameters, such as fluidity and molecular order, can be determined by these methods, the results are discussed on the basis of the recent theories of the role of the biochemical composition in the molecular structure and properties of membranes.

Oxygen adsorption and photoreduction on fractal melanin particles.

The main putative functions of melanins in living cells, that is photoprotection and dark or light-dependent oxido-reductive activity, still requires an interpretation which takes into account the micro-mesoscopic structure of native melanin particles. It is indeed well established that a different chemical composition of melanins, even if derived from different biosynthetic pathways, has only a little influence on the biological and physical properties of the solid aggregates, the common form in which the pigment is found [P.R. Crippa et al., Chemistry of melanins, in: A. Brossi (Ed.) The Alkaloids, vol. 36, Academic Press, New York, 1989, pp. 253-323]. In the present work a model for interfacial electron transfer is proposed describing the process of light induced superoxide formation through a monoelectronic reduction of dioxygen adsorbed on melanin solid surface. This process is presumed to be dependent on the surface fractal characteristics, and its kinetics must be interpreted as a heterogeneous interfacial reaction involving light produced carriers and the adsorbed acceptor, like in colloidal inorganic semiconductors such as TiO(2).

13C solid-state cross polarization/magic-angle-spinning nuclear magnetic resonance spectra of natural and synthetic melanins.

The availability of NMR spectrometers operating in cross polarization/magic angle spinning (CP-MAS) has provided a powerful tool for the structural elucidation of insoluble materials. In this 13C NMR study of eumelanins we report the first direct evidence of the presence of different chemical functionalities in synthetic and natural eumelanins. These spectra contain useful information for the characterization of melanins from different sources.

Photoacoustic studies of non-radiative relaxation of excited states in melanin.

Photoacoustic measurements made at various chopping frequencies on dense acqueous melanin suspensions have revealed a significant dependence upon pH and redox state. It is shown that such behaviour, differing from the simple predictions of the Rosencwaig-Gersho theory, can be explained in terms of finite carrier diffusion and recombination times. The implications of these findings with respect to the amorphous semiconductor model proposed to describe the dynamic role of epidermal melanin are discussed. From the experimental data, values of physical parameters were calculated which allow a qualitative correlation between chemical states and electronic behaviour and, consequently, some aspects of the molecular biology of the melanosome, founded on a rigorous base.

Quantitative radiation effects in hemoproteins and their constituents.

In order to verify the "radiation protection" effect of prosthetic groups in irradiated conjugated proteins and the influence of their electronic structure on intramolecular excitation transfer, two series of substances were examined. The first was composed of ferrihemoglobin and its constituents and the second was composed of similar hemoproteins with heme groups with major differences in electronic structure. The results point to a strong radiation protection effect of the heme groups and a dependence of radical yield of hemoproteins on the electronic structure of the heme. A possible interpretation of this latter effect is discussed.

Application of photoacoustic phase angle spectroscopy (phi AS) to eumelanins and pheomelanins.

A new technique, based on the measurement of the phase angle of the photoacoustic signal, was used for investigating the absorption spectra of melanins in the dry state. The main advantages of such a method are the insensitivity to scattering of the light and the applicability to nontransparent or highly adsorbing and thermally thick samples. The spectra obtained on different kinds of natural and synthetic melanins show much more details than the corresponding ones obtained spectrophotometrically on aqueous suspensions of the pigment. Some relevant features of the spectra still cannot be interpreted, yet we were able to show the presence in eumelanins of dopachrome at 475 nm and melanochrome at 540 nm, and in pheomelanins of compounds previously isolated from red chicken feathers. Moreover, the well known trend of the optical absorption, i.e., its decrease with increasing wavelength, was unambiguously confirmed.

Quenching of the excited states of 8-methoxypsoralen by synthetic Eumelanin.

The interaction of 8-methoxypsoralen (8-MOP) with synthetic eumelanin was investigated using static and time-resolved fluoresence and pulsed photoacoustic calorimetry. Spectroscopic data indicate the absence of interaction in the ground state, whereas the singlet excited state of 8-MOP is quenched by the pigment; the average fluorescence lifetimes are independent of the melanin concentration, thus indicating a static mechanism. Photoacoustic data show that the quenching process involves an increased intersystem crossing probability, which is almost unaffected by the presence of oxygen, as expected for a molecule essentially acting as a type I photosensitizing agent.

Oxidation of NADH by melanin: effect of UV light and copper ions.

The oxidation reaction of NADH with synthetic melanin from L-dopa was investigated under various physicochemical conditions both by spectrophotometric measurements and ESR spectroscopy. The different amounts of NADH oxidized and the effects on the formation and decay of melanin free radicals were compared. Some hypotheses on a common physical mechanism involved in electron transfer reaction and in electron excitation through a liquid-solid interface are presented.