Affinity states of biocides determine bioavailability and release rates in marine paints.

A challenge for the next generation marine antifouling (AF) paints is to deliver minimum amounts of biocides to the environment. The candidate AF compound medetomidine is here shown to be released at very low concentrations, ie ng ml(-1) day(-1). Moreover, the release rate of medetomidine differs substantially depending on the formulation of the paint, while inhibition of barnacle settlement is independent of release to the ambient water, ie the paint with the lowest release rate was the most effective in impeding barnacle colonisation. This highlights the critical role of chemical interactions between biocide, paint carrier and the solid/aqueous interface for release rate and AF performance. The results are discussed in the light of differential affinity states of the biocide, predicting AF activity in terms of a high surface affinity and preserved bioavailability. This may offer a general framework for the design of low-release paint systems using biocides for protection against biofouling on marine surfaces.

Vibrational study of tolazoline hydrochloride by using FTIR-Raman and DFT calculations.

Quantum mechanical (QM) calculations have been carried out in order to study the tolazoline hydrochloride theoretical structure and vibrational properties. This compound was characterized by infrared and Raman spectroscopies in the solid phase. For a complete assignment of the IR and Raman spectra, the density functional theory (DFT) calculations were combined with Pulay's Scaled Quantum Mechanics Force Field (SQMFF) methodology in order to fit the theoretical frequency values to the experimental ones. An agreement between theoretical and available experimental results was found. Three intense bands in the infrared spectrum characteristic of the protonated species of the compound were detected. Also, the possible charge-transfer and the topological properties for both benzyl and imidazoline rings were studied by means of Natural Bond Orbital (NBO) and Atoms in Molecules theory (AIM) investigation.

A diazonium ion cascade from the nitrosation of tolazoline, an imidazoline-containing drug.

Tolazoline (1-benzylimidazoline), a representative imidazoline-containing drug, reacts readily with nitrite in acetic acid to produce a complex product mixture. Fourteen compounds have been identified as products of this transformation when an 8-fold excess of HNO2 is used. The products, which include N-nitrosoamides, esters, alcohols, and phenylacetic acid, are rationalized as arising from a cascade of reactive diazonium ions. N-Nitrosotolazoline can be isolated from the nitrosation reaction in good yield when the mixture is extracted with CH2Cl2 as the transformation progresses. It nitrosates much more rapidly (50x) than tolazoline to give, among other products, the oxime [1-( N-nitroso-2-imidazolinyl)benzylidene]hydroxylamine, which can also be produced in good yield from the reaction of tolazoline with isopropyl nitrite. At low substrate and nitrite concentrations, the main reaction products are N-nitrosotolazoline, its decomposition product N-2-hydroxyethylphenylacetamide, the above-mentioned oxime, phenyl acetic acid, and 2-hydroxyethyl phenylacetate. The tolazoline nitrosation rate in three buffer systems has been determined at pH 3.4 and 37 degrees C ( kobs = 6.25 x 10 (-5) s (-1) in 0.5 M acetate buffer with a 10 * [NO2(-)] = 250 mM). Because N-nitrosotolazoline exhibits the chemical properties of a direct-acting mutagen and carcinogen, we have used the rate data to estimate its level of formation at nitrite concentrations <3 mM. Cursory examination of the nitrosation chemistry of oxymetazoline, a related drug, is primarily focused at its electron-rich aromatic ring.

Synthesis and biological activities of a new set of irreversibly acting 2-(4'-isothiocyanatobenzyl)imidazoline analogs in rat thoracic aorta.

IBI [2-(4'-isothiocyanatobenzyl)imidazoline, 3] has been shown to cause slow-onset, long-lasting contractions of rat thoracic aorta through a non-alpha-adrenergic receptor (non-alpha-AR) mediated mechanism. A series of IBI-related anlogs 7-14 and 16 was prepared to determine the structural requirements for the interaction with non-alpha-AR in rat aortic strips. All IBI analogs produced concentration-dependent contractile responses on rat thoracic aorta. Whereas the actions of analogs 7, 14, and 16 were partly mediated by alpha-ARs, the stimulatory activities of the remaining IBI analogs were unaffected by phenoxybenzamine pretreatment, suggesting that a non-alpha-adrenergic mechanism is involved. We have shown that the contractile actions of IBI and analogs 10-13 were not blocked with the imidazoline/guanidinium receptive site (IGRS) ligands idazoxan, cirazoline, or clonidine. However, the calcium channel blockers nifedipine or verapamil shifted the concentration-response curve of IBI and its analogs 10-13 to the right and reduced the maximal contractile responses. The action of IBI on rat thoracic aorta was reduced by the omission of extracellular calcium in the medium. These results suggest that the stimulatory activities of IBI and analogs 10-13 are not related to the activation of alpha-AR or IGRS receptors and are likely coupled to the voltage-dependent Ca2+ channels.