Studies on Transformations of H-Phosphonates into DNA Analogues Containing P-S or P-C Bonds

In this thesis, mechanistic and synthetic studies on transformations of H-phosphonates into DNA analogues containing P-S or P-C bonds are described. Configurational stability of dinucleoside H-phosphonates and the stereochemical course of their sulfurisation in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were investigated. In light of these studies, the reported stereoselective sulfurisation of dinucleoside H-phosphonates and benzoylphosphonates in the presence of DBU was proved to be incorrect. Efficient protocols for the synthesis of new nucleotide analogues with non-ionic C-phosphonate internucleotide linkages were developed. The synthesis of dinucleoside 2-pyridylphosphonates was successfully performed by a DBU-promoted reaction of H-phosphonate diesters with N-methoxypyridinium salts. The thio analogues, 2-pyridyl- and 4-pyridyl phosphonothioate diesters, could be obtained by modifying the reactions developed for their oxo counterparts. Dinucleoside 3-pyridylphosphonates were prepared via a palladium(0)-catalysed cross coupling strategy that could be extended also to the synthesis of nucleotide analogues with metal-complexing properties, i.e. terpyridyl- and bipyridylphosphonate derivatives. Oligonucleotides modified with pyridylphosphonate internucleotide linkages have been prepared and preliminary studies on their hybridisation properties and resistance towards enzymatic degradation were performed. Finally, nucleotidic units for the incorporation of pyridylphosphonate groups at the 5’-terminus of oligonucleotides were designed. Condensations of such units with a suitably protected nucleoside afforded after oxidation the expected dinucleoside (3’-5’)-phosphates with pyridylphosphonate monoester functions at the 5’-ends.

On the lifecycle of aerosol particles : Sources and dispersion over Scandinavia

Aerosol particles are likely important contributors to our future climate. Further, during recent years, effects on human health arising from emissions of particulate material have gained increasing attention. In order to quantify the effect of aerosols on both climate and human health we need to better quantify the interplay between sources and sinks of aerosol particle number and mass on large spatial scales. So far long-term, regional observations of aerosol properties have been scarce, but argued necessary in order to bring the knowledge of regional and global distribution of aerosols further. In this context, regional studies of aerosol properties and aerosol dynamics are truly important areas of investigation. This thesis is devoted to investigations of aerosol number size distribution observations performed through the course of one year encompassing observational data from five stations covering an area from southern parts of Sweden up to northern parts of Finland. This thesis tries to give a description of aerosol size distribution dynamics from both a quantitative and qualitative point of view. The thesis focuses on properties and changes in aerosol size distribution as a function of location, season, source area, transport pathways and links to various meteorological conditions. The investigations performed in this thesis show that although the basic behaviour of the aerosol number size distribution in terms of seasonal and diurnal characteristics is similar at all stations in the measurement network, the aerosol over the Nordic countries is characterised by a typically sharp gradient in aerosol number and mass. This gradient is argued to derive from geographical locations of the stations in relation to the dominant sources and transport pathways. It is clear that the source area significantly determine the aerosol size distribution properties, but it is obvious that transport condition in terms of frequency of precipitation and cloudiness in some cases even more strongly control the evolution of the number size distribution. Aerosol dynamic processes under clear sky transport are however likewise argued to be highly important. Southerly transport of marine air and northerly transport of air from continental sources is studied in detail under clear sky conditions by performing a pseudo-Lagrangian box model evaluation of the two type cases. Results from both modelling and observations suggest that nucleation events contribute to integral number increase during southerly transport of comparably clean marine air, while number depletion dominates the evolution of the size distribution during northerly transport. This difference is largely explained by different concentration of pre-existing aerosol surface associated with the two type cases. Mass is found to be accumulated in many of the individual transport cases studied. This mass increase was argued to be controlled by emission of organic compounds from the boreal forest. This puts the boreal forest in a central position for estimates of aerosol forcing on a regional scale.