title: Kinetic studies of redox and related reactions of some new isoalloxazines

authors: Gumbley, Stewart John

abstract: This thesis describes the synthesis of three new isoalloxazines with special structural characteristics which we hoped would, and in fact did, modify their chemical reactivity so as to improve our understanding of mechanisms of flavin reactions generally: kinetic studies of their reactions with a dithiol, reduced nicotinamide and sulphite were made.

A new general synthesis is described for the preparation of o-nitro-(N-alkylamino) aromatic compounds via nucleophilic displacement by alkylamine of a methoxy group ortho to a nitro group. Two new compounds, the isomers 1-(2'-hydroxyethylamino)-2-nitronaphthalene and 2-(2'-hydroxyethylamino)-1-nitronaphthalene, were prepared by this method.

These compounds were used to synthesize two isoalloxazines which each have an additional benzene ring fused either at the 6,7-bond of the isoalloxazine nucleus (7-(2'-hydroxyethyl)-10-methylnaphtho[1,2-g]pteridine- 9,11(7H,10H)-dione; isoalloxazine A) or at the 8,9-bond (12-(2'-hydroxyethyl)-9-methylnaphtho[2,1-g]pteridine- 8,10(9H,12H)-dione; isoalloxazine B). The third new isoalloxazine (10-(2'-hydroxyethyl)-3-methylbenzo[g]pteridine- 2,4(3H,10H)-dione; isoalloxazine C) was prepared by a conventional route.

Kinetic studies, the first recorded for isoalloxazines of the type of A and B, were undertaken for reactions with 1,3-dithio-2-propanol, with NADH and with sulphite.

In the case of the dithiopropanol reaction, a linear free-energy relationship was observed between the logarithm of the second order rate constant and the polarographic half-wave potential, E⅟₂ (slope 26 ± 1 V⁻¹). The conclusion drawn from this is that, if the redox reaction occurs through an addition-elimination sequence, the 5-, 6- and 8-positions are not essential centres for thiol oxidation.

In the case of the reaction with NADH, direct evidence was obtained for the formation of a kinetically important complex between the isoalloxazine and NADH from the observation of saturation kinetics. This is the first reported instance of the observation of such direct evidence for complex formation with NADH. The rate constants for the three isoalloxazines follow the reverse order expected from the E⅟₂ values and from the rates of reaction with DTP. The equilibrium constants (Kₑ) for the complexing of tryptophan with the isoalloxazines were measured by fluorescence quenching. A linear free-energy relationship was not observed between the logarithm of Kₑ and the logarithm of the rate constant for NADH oxidation. It was concluded that the unexpectedly high rate of reaction of A relative to that of B was due to the formation by A of a complex with NADH closer to the hydride acceptor site, the 5-position, than is the case for isoalloxazine B; and that the productivity of the complex therefore is markedly determined by the orientation of the NADH molecule with respect to the isoalloxazine within the complex.

The anaerobic nucleophilic addition reaction of sulphite with isoalloxazines A and C is a two step process of the form X⇌Y→Z, whereas the reaction with B is a single equilibrium step. The reduced isoalloxazine products from A and C are oxidized by molecular oxygen to new isoalloxazines but that from B is not. The new isoalloxazine from C reacts further with sulphite to yield a reduced species different from that of the anaerobic reaction, while the product from A does not react further. These observations provide support for the mechanism previously suggested in the literature for the reaction of sulphite with isoalloxazines. A small rate depression was observed for A relative to B and C in a plot of logarithm of rate constant against E ⅟₂. This is interpreted as being due to steric crowding at the 5-position caused by the α-hydrogen on the naphthalene moiety, an effect not observed in the dithiol reaction which more likely involves nucleophilic addition at the 4a- rather than the 5-position.

text: Kinetic studies of redox and related reactions of some new isoalloxazines This thesis describes the synthesis of three new isoalloxazines with special structural characteristics which we hoped would, and in fact did, modify their chemical reactivity so as to improve our understanding of mechanisms of flavin reactions generally: kinetic studies of their reactions with a dithiol, reduced nicotinamide and sulphite were made.

A new general synthesis is described for the preparation of o-nitro-(N-alkylamino) aromatic compounds via nucleophilic displacement by alkylamine of a methoxy group ortho to a nitro group. Two new compounds, the isomers 1-(2'-hydroxyethylamino)-2-nitronaphthalene and 2-(2'-hydroxyethylamino)-1-nitronaphthalene, were prepared by this method.

These compounds were used to synthesize two isoalloxazines which each have an additional benzene ring fused either at the 6,7-bond of the isoalloxazine nucleus (7-(2'-hydroxyethyl)-10-methylnaphtho[1,2-g]pteridine- 9,11(7H,10H)-dione; isoalloxazine A) or at the 8,9-bond (12-(2'-hydroxyethyl)-9-methylnaphtho[2,1-g]pteridine- 8,10(9H,12H)-dione; isoalloxazine B). The third new isoalloxazine (10-(2'-hydroxyethyl)-3-methylbenzo[g]pteridine- 2,4(3H,10H)-dione; isoalloxazine C) was prepared by a conventional route.

Kinetic studies, the first recorded for isoalloxazines of the type of A and B, were undertaken for reactions with 1,3-dithio-2-propanol, with NADH and with sulphite.

In the case of the dithiopropanol reaction, a linear free-energy relationship was observed between the logarithm of the second order rate constant and the polarographic half-wave potential, E⅟₂ (slope 26 ± 1 V⁻¹). The conclusion drawn from this is that, if the redox reaction occurs through an addition-elimination sequence, the 5-, 6- and 8-positions are not essential centres for thiol oxidation.

In the case of the reaction with NADH, direct evidence was obtained for the formation of a kinetically important complex between the isoalloxazine and NADH from the observation of saturation kinetics. This is the first reported instance of the observation of such direct evidence for complex formation with NADH. The rate constants for the three isoalloxazines follow the reverse order expected from the E⅟₂ values and from the rates of reaction with DTP. The equilibrium constants (Kₑ) for the complexing of tryptophan with the isoalloxazines were measured by fluorescence quenching. A linear free-energy relationship was not observed between the logarithm of Kₑ and the logarithm of the rate constant for NADH oxidation. It was concluded that the unexpectedly high rate of reaction of A relative to that of B was due to the formation by A of a complex with NADH closer to the hydride acceptor site, the 5-position, than is the case for isoalloxazine B; and that the productivity of the complex therefore is markedly determined by the orientation of the NADH molecule with respect to the isoalloxazine within the complex.

The anaerobic nucleophilic addition reaction of sulphite with isoalloxazines A and C is a two step process of the form X⇌Y→Z, whereas the reaction with B is a single equilibrium step. The reduced isoalloxazine products from A and C are oxidized by molecular oxygen to new isoalloxazines but that from B is not. The new isoalloxazine from C reacts further with sulphite to yield a reduced species different from that of the anaerobic reaction, while the product from A does not react further. These observations provide support for the mechanism previously suggested in the literature for the reaction of sulphite with isoalloxazines. A small rate depression was observed for A relative to B and C in a plot of logarithm of rate constant against E ⅟₂. This is interpreted as being due to steric crowding at the 5-position caused by the α-hydrogen on the naphthalene moiety, an effect not observed in the dithiol reaction which more likely involves nucleophilic addition at the 4a- rather than the 5-position.

year: 1976

title: Adaptive user interfaces for the Semantic Web

authors: Turner, Emmanuel King

subjects: Semantic Web

abstract: The Semantic Web aims to democratise data by making data open, shareable and recombinable (Berners-Lee, Hendler, & Lassila, 2001). To achieve these characteristics, Semantic Web data, different to data on the web, is structured. However, unlike traditional databases, the structure of Semantic Web data does not have to follow a single predefined schema. we believe that approaches for building user interfaces for data with a known structure are inadequate for the Semantic Web. In this thesis, we propose an adaptive user interface that categorises the Semantic Web data into groups and orders data according to user preference. Placing similar data items close together may make it easier for users to locate data items.

text: Adaptive user interfaces for the Semantic Web The Semantic Web aims to democratise data by making data open, shareable and recombinable (Berners-Lee, Hendler, & Lassila, 2001). To achieve these characteristics, Semantic Web data, different to data on the web, is structured. However, unlike traditional databases, the structure of Semantic Web data does not have to follow a single predefined schema. we believe that approaches for building user interfaces for data with a known structure are inadequate for the Semantic Web. In this thesis, we propose an adaptive user interface that categorises the Semantic Web data into groups and orders data according to user preference. Placing similar data items close together may make it easier for users to locate data items.

year: 2018

title: How many deaths were caused by the Tarawera eruption?

authors: Lowe, David J.

abstract: Most texts and brochures describing the Tarawera eruption of 10 June, l 886, record that it resulted in about 150 fatalities (e.g., Scott & Nairn, 1989; Ansell & Taber, 1996). Indeed, a figure of 153 deaths is recorded at the excellent new visitors' centre at the Buried Village, Te Wairoa, and in a number of other contexts. Elsewhere, numbers ranging from as few as about one hundred to possibly 'thousands' of deaths have been suggested (e.g., Houghton & Johnston, 1999).

text: How many deaths were caused by the Tarawera eruption? Most texts and brochures describing the Tarawera eruption of 10 June, l 886, record that it resulted in about 150 fatalities (e.g., Scott & Nairn, 1989; Ansell & Taber, 1996). Indeed, a figure of 153 deaths is recorded at the excellent new visitors' centre at the Buried Village, Te Wairoa, and in a number of other contexts. Elsewhere, numbers ranging from as few as about one hundred to possibly 'thousands' of deaths have been suggested (e.g., Houghton & Johnston, 1999).

year: 2001