K 114

Measured partition coefficients for parent and alkyl polycyclic aromatic hydrocarbons in 114 historically contaminated sediments: part 2. Testing the K(OC)K(BC) two carbon-type model.[Pubmed:18020686]

Environ Toxicol Chem. 2007 Dec;26(12):2505-16.

Polycyclic aromatic hydrocarbon (PAH) desorption partition coefficients between black carbon and water (K(BC)) were determined using 114 historically contaminated and background sediments from eight different rural and urban waterways. Black carbon was measured after oxidation at 375 degrees C for 24 h. Organic carbon-water partition coefficients (K(OC)) required for the calculation of K(BC) values were determined for two- to six-ring parent and C1- to C4-alkyl PAHs based on the lower range of measured K(OC) values from the same sediments and comparisons to literature K(OC) values. Approximately 2,050 log K(BC) values were determined on sediments having a range of total organic carbon from 0.3 to 42% by weight, black carbon from 0.1 to 40% by weight, and total PAH concentrations (U.S. Environmental Protection Agency 16 parent PAHs) from 0.2 to 8,600 microg/g. Contrary to expectations, PAH partitioning was not better explained using the combined K(OC) and K(BC) models rather than the simple K(OC) model (i.e., K(BC) values for each individual PAH ranged nearly three orders of magnitude). No effect of PAH concentration on measured K(BC) values was apparent. Values of K(BC) also showed no trends with total organic carbon, black carbon, or the presence or absence of a non- aqueous phase liquid. Multiple linear regression analysis with K(OC) and K(BC) as fitted values also failed to explain the variance of the experimental data (r(2) values typically less than 0.20, and standard errors greater than two orders of magnitude). These results demonstrate that models of PAH partitioning that account for different carbon types, although useful for understanding partitioning mechanisms, cannot yet be used to accurately predict PAH partitioning from historically contaminated sediments.

Mechanism of A beta(1-40) fibril-induced fluorescence of (trans,trans)-1-bromo-2,5-bis(4-hydroxystyryl)benzene (K114).[Pubmed:16313197]

Biochemistry. 2005 Dec 6;44(48):15937-43.

K114, (trans,trans)-1-bromo-2,5-bis(4-hydroxystyryl)benzene, is a fluorescent Congo Red analogue that binds tightly to amyloid fibrils, but not the monomeric proteins, with a concomitant enhancement in fluorescence. The mechanism for the low aqueous fluorescence and the subsequent enhancement by A beta(1-40) fibrils was investigated by fluorescence spectroscopy and binding analysis. K114's unusually low buffer fluorescence is due to self-quenching in sedimentable aggregates or micelles which upon interacting with amyloid fibrils undergo an enhancement in fluorescence intensity and shifts in the excitation and emission spectra. These spectral changes are suggestive of a stabilization of the phenolate anion, perhaps by hydrogen bonding, rather than an increase in the microenvironment dielectric constant or dye immobilization. 1,4-Bis(4-aminophenylethenyl)-2-methoxybenzene, which lacks the phenol moiety, and X-34, which contains a stabilized phenol (pK approximately 13.4), do not display the phenolate anion fluorescence in the presence of fibrils. The apparent affinity of K114 for fibril binding is 20-30 nM with a stoichiometry of 2.2 mol of K114/mol of A beta(1-40) monomer. Competition studies indicate that K114 and Congo Red share a site, but K114 does not bind to sites on A beta(1-40) fibrils for neutral benzothiazole (BTA-1), cationic thioflavin T, or the hydrophobic (S)-naproxen and (R)-ibuprofen molecules. Comparison of benzothiazole binding stoichiometry which has been suggested to reflect disease-relevant amyloid structures to that of Congo Red analogues which reflect total fibril content may be useful in defining biologically pertinent conformational forms of amyloid.

A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114.[Pubmed:12950445]

J Neurochem. 2003 Sep;86(6):1359-68.

Proteinaceous inclusions with amyloidogenic properties are a common link between many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Histological and in vitro studies of amyloid fibrils have advanced the understanding of protein aggregation, and provided important insights into pathogenic mechanisms of these neurodegenerative brain amyloidoses. The classical amyloid dyes Congo Red (CR) and thioflavin T and S, have been used extensively to detect amyloid inclusions in situ. These dyes have also been utilized to monitor the maturation of amyloid fibrils assembled from monomer subunits in vitro. Recently, the compound (trans,trans)-1-bromo-2,5-bis-(3- hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB), derived from the structure of CR, was shown to bind to a wide range of amyloid inclusions in situ. More importantly it was also used to label brain amyloids in live animals. Herein, we show that an analogue of BSB, (trans,trans)-1-bromo-2,5-bis-(4-hydroxy)styrylbenzene (K114), recognizes amyloid lesions, and has distinctive properties which allowed the quantitative monitoring of the formation of amyloid fibrils assembled from the amyloid-beta peptide, alpha-synuclein, and tau.