Dioxygenase-catalysed mono-, di- and tri-oxygenation of dialkyl sulfides and thioacetals: chemoenzymatic synthesis of enantiopure cis-diol sulfoxides

Toluene dioxygenase (TDO)-catalysed monooxygenation of methylsulfanylmethyl phenyl sulfide 1 and methylsulfanylmethyl 2-pyridyl sulfide 4, using whole cells of Pseudomonas putida UV4, occurred exclusively at the alkyl aryl sulfur centre to yield the alkyl aryl sulfoxides 2 and 5 respectively. These sulfoxides, accompanied by the dialkyl sulfoxides 3 and 6, were also obtained from naphthalene dioxygenase (NDO)-catalysed sulfoxidation of thioacetals 1 and 4 using intact cells of P. putida NCIMB 8859. Enzymatic oxidation of methyl benzyl sulfide 7, 2-phenyl-1,3-dithiane 19, and 2-phenyl-1,3-dithiolane 23, using TDO, gave the corresponding dialkyl sulfoxides 8, 20 and 24 as minor bioproducts. TDO-catalysed dioxygenation of the alkyl benzyl sulfides 7, 15 and 17 and the thioacetals 19 and 23, with P. putida UV4, yielded the corresponding enantiopure cis-dihydrodiols 9, 16, 18, 21 and 25 as major metabolites and cis-dihydrodiol sulfoxides 14, 22 and 26 as minor metabolites, resulting from a tandem trioxygenation of substrates 7, 19 and 23 respectively. Chemical oxidation, of the enantiopure cis-dihydrodiol sulfides 9, 16, 18 and 21 with dimethyldioxirane (DMD), gave separable mixtures of the corresponding pairs of cis-dihydrodiol sulfoxide diastereoisomers 14 and 27, 28 and 29, 30 and 31, 22 and 32. While dialkyl sulfoxide bioproducts 3, 6, 20 and 24 were of variable enantiopurity (27-greater than or equal to 98% ee), alkyl aryl monosulfoxides 2 and 5, cis-dihydrodiols 9, 16, 18, 21 and 25 and cis-dihydrodiol sulfoxide bioproducts 14, 22 and 26 were all single enantiomers (greater than or equal to 98% ee). The absolute configurations of the products, obtained from enzyme-catalysed (TDO and NDO) and chemical (DMD) oxidation methods, were determined by stereochemical correlation, circular dichroism, and X-ray crystallographic methods.

DPP IV resistance and insulin releasing activity of a novel di-substituted analogue of glucose-dependent insulinotropic polypeptide, (Ser(2)-Asp(13))GIP

Structure-function studies suggest that preservation of the N-terminus and secondary structure of glucose-dependent insulinotropic polypeptide (GIP) is important for biological activity. Therefore, a novel di-substituted analogue of GIP, (Ser(2)-Asp(13))GIP, containing a negatively charged Asp residue in place of an Ala in position 13, seas synthesised and evaluated for in vitro biological activity. Incubation with dipeptidyl peptidase IV (DPP IV) showed the half-lives of GIP and (Ser(2)-Asp(13))GIP to be 2.3 and >4 h, respectively. Insulin releasing studies in clonal pancreatic BRIN-BD11 cells demonstrated that (Ser(2)-Asp(13))GIP (10(-12) to 10(-7) mol/l) was significantly less potent (60-90%; P

Formation of Novel Di-Nuclear Lanthanide Luminescent Sm(III), Eu(III) and Tb(III) Triple Stranded Helicates from a C2 Symmetrically 2,6-Dicarboxylic Amide based 1,3-Xylene Ligand in CH3CN

The synthesis of the C2-symmetrical ligand 1 consisting of two naphthalene units connected to two pyridine-2,6-dicarboxamide moieties linked by a xylene spacer and the formation of LnIII-based (Ln1/4 Sm, Eu, Tb, and Lu) dimetallic helicates [Ln2 · 13] in MeCN by means of a metal-directed synthesis is described. By analyzing the metal-induced changes in the absorption and the fluorescence of 1, the formation of the helicates, and the presence of a second species [Ln2 · 12] was confirmed by nonlinear- regression analysis. While significant changes were observed in the photophysical properties of 1, the most dramatic changes were observed in the metal-centred lanthanide emissions, upon excitation of the naphthalene antennae. From the changes in the lanthanide emission, we were able to demonstrate that these helicates were formed in high yields (ca. 90% after the addition of 0.6 equiv. of LnIII), with high binding constants, which matched well with that determined from the changes in the absorption spectra. The formation of the LuIII helicate, [ Lu2 · 13 ] , was also investigated for comparison purposes, as we were unable to obtain accurate binding constants from the changes in the fluorescence emission upon formation of [Sm2 · 13], [Eu2 · 13], and [Tb2 · 13].

Linking past cultural developments to palaeoenvironmental changes in Estonia

Connections between environmental and cultural changes are analysed in Estonia during the past c. 4,500 years. Records of cereal-type pollen as (agri)cultural indices are compared with high-resolution palaeohydrological and annual mean temperature reconstructions from a selection of Estonian bogs and lakes (and Lake Igelsjon in Sweden). A broad-scale comparison shows increases in the percentage of cereal-type pollen during a decreasing trend in annual mean temperatures over the past c. 4,300 years, suggesting a certain independence of agrarian activities from environmental conditions at the regional level. The first cereal-type pollen in the region is found from a period with a warm and dry climate. A slow increase in pollen of cultivated land is seen around the beginning of the late Bronze Age, a slight increase at the end of the Roman Iron Age and a significant increase at the beginning of the Middle Ages. In a few cases increases in agricultural pollen percentages occur in the periods of warming. Stagnation and regression occurs in the periods of cooling, but regression at individual sites may also be related to warmer climate episodes. The cooling at c. 400-300 cal b.p., during the 'Little Ice Age' coincides with declines in cereal-type and herb pollen curves. These may not, however, be directly related to the climate change, because they coincide with war activities in the region.

Peat multi-proxy data from Mannikjarve bog as indicators of late Holocene climate changes in Estonia

As part of a wider project on European climate change over the past 4500 years, a 4.5-m peat core was taken from a lawn microform on Mannikjarve bog, Estonia. Several methods were used to yield proxy-climate data: (i) a quadrat and leaf-count method for plant macrofossil data, (ii) testate amoebae analysis, and (iii) colorimetric determination of peat humification. These data are provided with an exceptionally high resolution and precise chronology. Changes in bog surface wetness were inferred using Detrended Correspondence Analysis (DCA) and zonation of macrofossil data, particularly concerning the occurrence of Sphagnum balticum, and a transfer function for water-table depth for testate amoebae data. Based on the results, periods of high bog surface wetness appear to have occurred at c. 3100, 3010-2990, 2300, 1750-1610, 1510, 14 10, 1110, 540 and 3 10 cal. yr BP, during four longer periods between c. 3170 and 2850 cal. yr BP, 2450 and 2000 cal. yr BP, 1770 and 1530 cal. yr BP and in the period from 880 cal. yr BP until the present. In the period between 1770 and 1530 cal. yr BP. the extension or initiation of a hollow microtope occurred, which corresponds with other research results from Mannikjarve bog. This and other changes towards increasing bog surface wetness may be the responses to colder temperatures and the predominance of a more continental climate in the region, which favoured the development of bog microdepressions and a complex bog microtopography. Located in the border zone of oceanic and continental climatic sectors, in an area almost without land uplift, this study site may provide valuable information about changes in palaeohydrological and palaeoclimatological conditions in the northern parts of the eastern Baltic Sea region.

Poly[[dibromomercury(II)]-di-mu-pyrazine-kappa N-4 : N ']

The crystal structure of [HgBr2(Pyp)(2)](n) (Pyp = pyrazine, C4H4N2) consists of almost linear HgBr2 molecules which are linked by pyrazine molecules to form double strands of a coordination polymer in the [010] direction. The Hg and Br atoms lie on mirror planes.