Phoenix, Arizona, revisited : indications of aerosol effects on O{sub 3}, NO{sub 2}, UV-B, and NO{sub 3}.

Fine particulate matter and tropospheric ozone levels are of concern because of their potential for health impacts, as well as their radiative effects. Both ozone and PM-2.5 standards are being exceeded in many urban and regional areas where transport and background levels can appreciably affect observed concentrations. Anthropogenic nitrogen oxides and other primary pollutant species can interact with natural organics to form secondary aerosol products via synthesis of nitric acid and its subsequent reaction with ammonia to yield ammonium nitrate. In addition, natural organics and lower-reactivity organic compounds, particularly aromatic species and monoterpenes, can generate secondary organic aerosols, both of which contribute to the formation of PM-2.5. Long-range transport and chemical transformation of hydrocarbons and NO{sub x} via both photochemical reactions and nighttime chemistry can generate significant regional levels of ozone (O{sub 3}) and other oxidants, such as peroxyacyl nitrates

Multifunctional Nanoparticles Based on a Single-Molecule Modification for the Treatment of Drug-Resistant Cancer

Multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Tocopheryl polyethylene glycol 1000 succinate (TPGS) has been extensively explored for the treatment of MDR in cancer because of its ability to inhibit P-glycoprotein. Here, we have established multifunctional nanoparticles (MFNPs) using a single-molecule modification of TPGS, which can deliver a hydrophobic drug, paclitaxel (PTX), and a hydrophilic drug, fluorouracil (5-FU), and overcome MDR in cancer. Our data indicated that, when delivered into a PTX-resistant cell line using MFNPs, the combination of PTX and 5-FU was more cytotoxic than each agent individually

D-α-tocopheryl polyethylene glycol 1000 succinate: a view from FTICR MS and Tandem MS

d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is an important polymeric excipient frequently used in drug formulation. However, differing compositions of the TPGS samples between batches are believed to result in variable performance of the formulated product. Herein, a high performance method using Fourier-transform ion cyclotron resonance (FTICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) to analyze the composition of TPGS samples and the structure of TPGS was established. Aided by high mass accuracy and high resolution, the full MS overview of TPGS is able to provide composition information, and diagnostic fragments from collisionally activated dissociation (CAD) and electron capture dissociation (ECD) MS/MS can be used for the identification of the TPGS structure. ECD and CAD show different preferences in bond cleavage, and an interesting cross-ring cleavage was generated by CAD. Fragmentation information from ECD/ECD MS3 is useful for providing confidence in the results. The influence of different ionization agents (Na+, Li+, and Ag+) on fragmentation of TPGS was investigated with the silver adduct providing different fragments. In addition to the methodology study, the MS and MS/MS results from four batches of TPGS samples from two manufacturers were compared. This method can be utilized for the composition and structure study of many other polymeric compounds. FTICR MS/MS demonstrated its promising role as a structural characterization tool complementary to traditional spectroscopy techniques

Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate.

Trypanothione reductase is a flavoenzyme unique to trypanosomatid parasites. Here we show that unsaturated Mannich bases irreversibly inactivate trypanothione reductase from Trypanosoma cruzi, the causative agent of Chagas' disease. The inhibitory potency of the compounds strongly increased upon storage of the DMSO stock solutions. HPLC, NMR, and mass spectrometry data of potential intermediates revealed a divinyl ketone as the active compound inactivating the enzyme. ESI- and MALDI-TOF mass spectrometry of trypanothione reductase modified by the Mannich base or the divinyl ketone showed specific alkylation of the active site Cys52 by a 5-(2'chlorophenyl)-3-oxo-4-pentenyl substituent. The reaction mechanism and the site of alkylation differ from those in Plasmodium falciparum thioredoxin reductase where the C-terminal redox active dithiol is modified. After deamination, unsaturated Mannich bases are highly reactive in polycondensation with trypanothione. Interaction of these compounds with both trypanothione and trypanothione reductase could account for their potent trypanocidal effect against Trypanosoma brucei