Role of sulphuric acid, ammonia and galactic cosmic rays in atmospheric aerosol nucleation.

Atmospheric aerosols exert an important influence on climate through their effects on stratiform cloud albedo and lifetime and the invigoration of convective storms. Model calculations suggest that almost half of the global cloud condensation nuclei in the atmospheric boundary layer may originate from the nucleation of aerosols from trace condensable vapours, although the sensitivity of the number of cloud condensation nuclei to changes of nucleation rate may be small. Despite extensive research, fundamental questions remain about the nucleation rate of sulphuric acid particles and the mechanisms responsible, including the roles of galactic cosmic rays and other chemical species such as ammonia.

Evidence for the role of organics in aerosol particle formation under atmospheric conditions.

New particle formation in the atmosphere is an important parameter in governing the radiative forcing of atmospheric aerosols. However, detailed nucleation mechanisms remain ambiguous, as laboratory data have so far not been successful in explaining atmospheric nucleation. We investigated the formation of new particles in a smog chamber simulating the photochemical formation of H(2)SO(4) and organic condensable species.

Determination of the aerosol yield of isoprene in the presence of an organic seed with carbon isotope analysis.

We examined a new method to determine the aerosol yield of precursors of secondary organic aerosols in the presence of organic seed particles. To distinguish between the oxidation products of the compound in question and the organic seed, the compound was labeled with stable isotopes and aerosol samples were analyzed by isotope ratio mass spectrometry (IRMS). 13C labeled isoprene was obtained from isoprene emitting plants that were exposed to (13)CO2.

Synthesis of 2-amino-5-benzoyl-4-(2-furyl)thiazoles as adenosine A(2A) receptor antagonists.

The discovery and synthesis of a series of 2-amino-5-benzoyl-4-(2-furyl)thiazoles as adenosine A(2A) receptor antagonists from a small-molecule combinatorial library using a high-throughput radioligand-binding assay is described. Antagonists were further characterized in the A(2A) binding assay and an A(1) selectivity assay. Selected examples exhibited excellent affinity for A(2A) and good selectivity versus the A(1) receptor.

Sulfonamido-aryl ethers as bradykinin B1 receptor antagonists.

The synthesis and identification of sulfonamido-aryl ethers as potent bradykinin B1 receptor antagonists from a approximately 60,000 member encoded combinatorial library are reported. Two distinct series of compounds exhibiting different structure-activity relationships were identified in a bradykinin B1 whole-cell receptor-binding assay. Specific examples exhibit K(i) values of approximately 10nM.

Using proton transfer reaction mass spectrometry for online analysis of secondary organic aerosols.

Proton-transfer-reaction mass spectrometry (PTR-MS) is a useful tool in ambient trace gas analysis, especially for the analysis of oxygenated volatile organic compounds (OVOC). Many OVOCs are produced during photooxidation of volatile organic compounds and contribute to both the gas phase and secondary organic aerosols (SOA). The inlet system of the PTR-MS instrument was modified to allow also for the measurement of the particulate phase of an aerosol with a high time resolution.

O/C and OM/OC ratios of primary, secondary, and ambient organic aerosols with high-resolution time-of-flight aerosol mass spectrometry.

A recently developed method to rapidly quantify the elemental composition of bulk organic aerosols (OA) using a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) is improved and applied to ambient measurements. Atomic oxygen-to-carbon (O/C) ratios characterize the oxidation state of OA, and O/C from ambient urban OA ranges from 0.2 to 0.

Combined determination of the chemical composition and of health effects of secondary organic aerosols: the POLYSOA project.

Epidemiological studies show a clear link between increased mortality and enhanced concentrations of ambient aerosols. The chemical and physical properties of aerosol particles causing these health effects remain unclear. A major fraction of the ambient aerosol particle mass is composed of secondary organic aerosol (SOA).

Successful screening of large encoded combinatorial libraries leading to the discovery of novel p38 MAP kinase inhibitors.

Screening of more than 2 million compounds comprising 41 distinct encoded combinatorial libraries revealed a novel structural class of p38 mitogen-activated protein (MAP) kinase inhibitors. The methodology used for screening large encoded combinatorial libraries combined with the statistical interpretation of screening results is described. A strong preference for a particular triaminotriazine aniline amide was discovered based on biological activity observed in the screening campaign.

Discovery and characterization of triaminotriazine aniline amides as highly selective p38 kinase inhibitors.

The p38 mitogen-activated protein (MAP) kinases are a family of serine/threonine protein kinases that play important roles in cellular responses to inflammation and external stress. Inhibitors of the p38 MAP kinase have shown promise for potential treatment of inflammatory disorders such as rheumatoid arthritis, acute coronary syndrome, psoriasis, and Crohn's disease. We identified a novel class of p38 inhibitors via high-throughput screening.

Real-time measurement of oligomeric species in secondary organic aerosol with the aerosol time-of-flight mass spectrometer.

Real-time detection of oligomers in secondary organic aerosols has been carried out with an aerosol time-of-flight mass spectrometer sampling particles generated in a smog chamber. The photooxidation products of 1,3,5-trimethylbenzene and NOx were studied over a range of initial 1,3,5-trimethylbenzene concentrations (137-1180 ppb), while keeping the 1,3,5-trimethylbenzene to NOx ratio nearly constant. The photooxidation products of a mixture of alpha-pinene (initial concentration 191 ppb), 1,3,5-trimethylbenzene (60 ppb), and NOx were also investigated.

5-Cyanopyrimidine derivatives as a novel class of potent, selective, and orally active inhibitors of p38alpha MAP kinase.

A novel class of 5-cyanopyrimidine-based inhibitors of p38alpha MAP kinase has been investigated. Analogues optimized through SAR iterations display low nanomolar enzymatic and cellular activity. The in vivo efficacy of this class of p38 inhibitors was demonstrated by 3a and 3b (>50% reduction in TNF levels when orally dosed at 5 mg/kg, 5 h prior to LPS administration in an acute murine model of inflammation).

The discovery of novel chemotypes of p38 kinase inhibitors.

In the late 1970s and the early 1980s the initial p38 chemotype, the triaryl imidazoles, was discovered as an off-target effect during the development of cyclooxygenase and 5-lipoxygenase inhibitors long before the identity of the p38 kinase was known. During the last 10 years a number of novel p38 chemotypes were discovered via high throughput screening. More recently, the first series of p38 inhibitors discovered by xray crystallographic and virtual screening was announced.

Effect of humic and fulvic acid concentrations and ionic strength on copper and lead binding.

We investigated the influence of humic and fulvic acid concentration (in the range of 1-1000 mg/L) on the binding of the two trace metals Cu(II) and Pb(II). The ability of the non-ideal competitive adsorption (NICA)-Donnan model to correctly predict Cu and Pb binding at low humic or fulvic acid concentration and lower ionic strength (0.01 M NaNO3), based on model parameters obtained from experiments conducted at high humic or fulvic acid concentrations (approximately 1000 mg/L) and higher ionic strength (0.

The discovery of orally active triaminotriazine aniline amides as inhibitors of p38 MAP kinase.

A new structural class of triaminotriazine aniline amides possessing potent p38 enzyme activity has been discovered. The initial hit (compound 1a) was identified through screening the Pharmacopeia ECLiPS compound collection. SAR modification led to the identification of a short acting triaminotriazine aniline methoxyamide (compound 1m) possessing in vitro and in vivo oral activity in animal models of acute and chronic inflammatory disease.

Thermodynamic analysis of receptors based on guanidinium/boronic acid groups for the complexation of carboxylates, alpha-hydroxycarboxylates, and diols: driving force for binding and cooperativity.

The thermodynamics of guanidinium and boronic acid interactions with carboxylates, alpha-hydroxycarboxylates, and diols were studied by determination of the binding constants of a variety of different guests to four different hosts (7-10). Each host contains a different combination of guanidinium groups and boronic acids. The guests included molecules with carboxylate and/or diol moieties, such as citrate, tartrate, and fructose, among others.

Ion-pairing molecular recognition in water: aggregation at low concentrations that is entropy-driven.

Investigations into the thermodynamic parameters that characterize the binding of citrate to tris-guanidinium host 1 in water are reported. The parameters K(a), DeltaH degrees, DeltaS degrees, and DeltaG degrees for the binding event were quantified using isothermal titration calorimetry (ITC) techniques. The 1:1 binding stoichiometry was verified by a Job plot derived from NMR data, and the microcalorimetry data was collected for solutions of 1 and citrate ranging from 1 to 100 mM using phosphate buffer concentrations of 5 and 103 mM.

A Chemosensor for Citrate in Beverages.

Competitive binding like that in immunoassays is the principle behind the chemosensor based on receptor 1, which was used to measure the concentration of citrate (2) in a series of common beverages. Citrate displaces the fluorescent colorimetric probe 5-carboxylfluorescein (3) from 1, and the process can be monitored by UV or fluorescence spectroscopy.