Photocytotoxic 3d-Metal Scorpionates with a 1,8-Naphthalimide Chromophore Showing Photoinduced DNA and Protein Cleavage Activity

Ternary 3d-metal complexes of formulation [M(Tp(Ph))(py-nap)](ClO4)(1-3), where M is Co(II) (1), Cu(II) (2), and Zn(II) (3); Tp(Ph) is anionic tris (3-phenylpyrazolyl)borate; and py-nap is a pyridyl ligand with a conjugated 1,8-naphthalimide moiety, have been prepared from the reaction of metal perchlorate with KTp(Ph) and py-nap in CH2Cl2. The complexes have been characterized from analytical and physicochemical data. The complexes are stable in solution as evidenced from the electrospray ionization mass spectrometry data. The complexes show good binding propensity with calf thymus (CT) DNA, giving binding constant (K-b) values of similar to 10(5) M-1 and a molecular ``light-switch'' effect that results in an enhancement of the emission intensity of the naphthalimide chromophore on binding to CT DNA. The complexes do not show any hydrolytic cleavage of DNA. They show poor chemical nuclease activity in the presence of 3-mercaptopropionic acid or hydrogen peroxide (H2O2). The Co(II) and Cu(II) complexes exhibit oxidative pUC19 DNA cleavage activity in UV-A light of 365 rim. The Zn(II) complex shows moderate DNA photocleavage activity at 365 nm. The Cu(II)complex 2 displays photoinduced DNA cleavage activity in red light of 647.1 nm and 676 rim and near-IR light of >750 rim. A mechanistic studyin UV-A and visible light suggests the involvement of the hydroxyl radical as the reactive species in the DNA photocleavage reactions. The complexes also show good bovine serum albumin (BSA) protein binding propensity, giving K-BSA values of similar to 10(5) M-1. Complexes 1 and 2 display significant photoinduced BSA cleavage activity in UV-A light. The Co(II) complex 1 shows a significant photocytotoxic effect in HeLa cervical cancer cells on exposure to UV-A light of 365 nm, giving an IC50 value of 32 mu M. The IC50 value for the py-nap ligand alone is 41.42 mu m in UV-A light. The IC50 value is >200 mu M in the dark, indicating poor dark toxicity of 1. The Cu(II) complex 2 exhibits moderate photocytotoxicity and significant dark toxicity, giving IC50 values of 18.6 mu m and 29.7 mu m in UV-A light and in the dark, respectively.

Sequence of reactions leading to cytochrome-p-450 synthesis-effect of drugs

The effect of phenobarbital on the rates of the synthesis of the protein and heme moieties of cytochrome P-450 has been studied. For this purpose, cytochrome P-450 has been partially purified as its P-420 derivative and the labeled amino acid incorporation into the protein has been studied after subjecting a partially purified preparation to sodium dodecyl sulfate gel electrophoresis. The incorporation studies into the protein species after sodium dodecyl sulfate gel electrophoresis reveal that the drug primarily accelerates the rate of apoprotein synthesis followed by an increase in the rate of heme synthesis. The messenger for apocytochrome P-450 appears to be fairly stable.

Studies of phosphazenes. Part I. Reactions of octachlorocyclotetraphosphazatetraene with ethylamine

The reaction of octachlorocyclotetraphosphazatetraene, N4P4Cl8, with ethylamine has been investigated. Seven derivatives, N4P4Cl8–n(NHEt)n[n= 1, 2 (two isomers), 3, 4 (two isomers), and 8] have been isolated and their structures established by 1H and 31P n.m.r. spectroscopy. A non-geminal chlorine atom replacement scheme is observed. Attempts to prepare penta- or hexa-ethylamino derivatives were unsuccessful: only sticky, non-crystalline resins were obtained from 1 : 10 or 1 : 12 reactions. The preparation and n.m.r. spectroscopic data of mixed ethylamino(methoxy)-derivatives. N4P4(NHEt)–8-n(OMe)n[n= 6, 4 (two isomers)], and an ethylamino-(dimethylamino)-derivative, N4P4(NHEt)2(NMe2)6, are generally consistent with the proposed structures. The reaction pattern is discussed.

The Macroeconomic Effects of Fiscal Policy in a Small Open Economy under a Flexible Exchange Rate Regime

This licentiate's thesis analyzes the macroeconomic effects of fiscal policy in a small open economy under a flexible exchange rate regime, assuming that the government spends exclusively on domestically produced goods. The motivation for this research comes from the observation that the literature on the new open economy macroeconomics (NOEM) has focused almost exclusively on two-country global models and the analyses of the effects of fiscal policy on small economies are almost completely ignored. This thesis aims at filling in the gap in the NOEM literature and illustrates how the macroeconomic effects of fiscal policy in a small open economy depend on the specification of preferences. The research method is to present two theoretical model that are extensions to the model contained in the Appendix to Obstfeld and Rogoff (1995). The first model analyzes the macroeconomic effects of fiscal policy, making use of a model that exploits the idea of modelling private and government consumption as substitutes in private utility. The model offers intuitive predictions on how the effects of fiscal policy depend on the marginal rate of substitution between private and government consumption. The findings illustrate that the higher the substitutability between private and government consumption, (i) the bigger is the crowding out effect on private consumption (ii) and the smaller is the positive effect on output. The welfare analysis shows that the less fiscal policy decreases welfare the higher is the marginal rate of substitution between private and government consumption. The second model of this thesis studies how the macroeconomic effects of fiscal policy depend on the elasticity of substitution between traded and nontraded goods. This model reveals that this elasticity a key variable to explain the exchange rate, current account and output response to a permanent rise in government spending. Finally, the model demonstrates that temporary changes in government spending are an effective stabilization tool when used wisely and timely in response to undesired fluctuations in output. Undesired fluctuations in output can be perfectly offset by an opposite change in government spending without causing any side-effects.

ESR study of exchange coupled pairs in copper diethyldithiocarbamate—explanation of the low temperature hyperfine anomaly

A study of the hyperfine interaction in the ESR of Cu-Cu pairs in single crystals of copper diethyldithiocarbamate as a function of temperature has shown distinct differences in the hyperfine structure in the two fine structure transitions at 20 K, the spectrum not having the same hyperfine intensity pattern in the low field fine structure transition in contrast to that of the high field transition. The details of the structure of both the fine structure transitions in the 20 K spectrum have now been explained by recognizing the fact that the mixing of the nuclear spin states caused by the anisotropic hyperfine interaction affects the electron spin states | + 1 > and | −> differently. This has incidentally led to a determination of the sign ofD confirming the earlier model. The anomalous hyperfine structure is found to become symmetric at 77 K and 300 K. It is proposed that the reason for this lies in the dynamics of spin-lattice interaction which limits the lifetime of the spin states in each of the electronic levels | − 1 >, | 0 > and | + 1 > The estimate of spin-lattice relaxation time agrees with those indicated from other studies. The model proposed here for the hyperfine interaction of pairs in the electronic triplet state is of general validity.

Reinvestigation of the reactions of hexachlorocyclotriphosphazatriene with ethylenediamine and ethanolamine

Abstract is not available.

Contribution of the condensed-phase reactions in the combustion of solid rocket fuels

Abstract is not available.

Direct Synthesis of Functionalized Unsymmetrical beta-Sulfonamido Disulfides by Tetrathiomolybdate Mediated Aziridine Ring-Opening Reactions

Direct synthesis of unsymmetrical beta-sulfonamido disulfides by ring-opening of aziridines by using benzyltriethyl-ammonium tetrathiomolybdate 1 as a sulfur transfer reagent in the presence of symmetrical disulfides as thiol equivalents has been reported. Reaction of benzyl and alkyl disulfides gave unsymmetrical beta-sulfonamido disulfides as the only product in very good yields. From the Study, it has been observed that aryl disulfides containing p-NO2, p-Cl, and p-CN led to the formation of the corresponding beta-aminosulfides as the exclusive products. However, un-substituted aryl disulfides and the one containing electron-donating substituents (p-Me) provide a mixture of beta-sulfonamido mono- and disulfides as the products.

Tributyltin chloride-sodium cyanoborohydride mediated tandem radical cyclisation-reductive demethoxylation sequence

Reaction of the bromoketals 3, 7a-g and 11 with tri-n-butyltin chloride and sodium cyanoborohydride in the presence of a catalytic amount of AIBN furnished the ethers 5, 8a-g and 13 via a tandem sequence comprising of a radical cyclisation reaction and tri-n-butylhalostannane and sodium cyanoborohydride mediated reductive demethoxylation of the resulting cyclic ketals.

Non-enzymatic reactions involving vitamin B6: Spectroscopic investigations on the effect of pH and metal ions on the decyclization reactions of the pyridoxal-histamine cyclized Schiff base

The effect of pH and metal ions (Cu2+, Zn2+, Cd2+, Mn2+, Cr3+, Co3+, and Mg2+) on the decyclization reactions of pyridoxal-histamine cyclized Schiff base has been studied using electronic spectroscopy. The study reveals that the cyclization reaction is irreversible with respect to pH and metal ions. Interest in this work derives from the possible involvement of cyclization reactions in the inhibitory activity of a number of pyridoxal-dependent enzymes.

An NAD(P)(+)-dependent secondary-alcohol dehydrogenase of Alcaligenes eutrophus: Purification, characterization and its application for the production of chiral alcohols

A soil micro-organism identified as Alcaligenes eutrophus capable of utilizing nerolidol, a sesquiterpene alcohol as the sole source of carbon, contains an inducible NAD(P)(+)-linked secondary-alcohol dehydrogenase (SADH), The enzyme was purified 252-fold from crude cell-free extract by a combination of salt precipitation, ion-exchange and affinity-matrix chromatography, Native and SDS/PAGE PAGE of the purified enzyme showed a single protein band and the enzyme appears to be a homotetramer having an apparent molecular mass of 139 kDa comprising four identical subunits of 38.5 kDa, The isoelectric point (pi) of SADH was determined to be 6.2, Depending on pH of the reaction media, the enzyme carried out both oxidation and reductions of various terpenoids and steroids, At pH 5.5, the enzyme catalysed the stereospecific reduction of prochiral ketones to optically active (S)-alcohols and the oxidation reaction was predominated over the former at pH 9.5, NADP(+) and NADPH were respectively preferred over NAD(+) and NADH for oxidation and reduction reactions, The K-m values for testosterone, NADP(+) and NAD(+) were 11.8, 55.6, and 122 mu M respectively, Neither enzyme was significantly inhibited by metal-binding agents, but some thiol-blocking compounds inhibited it, SADH tolerates moderate concentrations of water-miscible organic solvents such as ethanol, methanol, acetone and dioxan, Some of the properties of this enzyme were found to be significantly different from those thus far described.

Complexity of collaborative work in residential aged care facilities: An analysis of information exchange for medication management

Information exchange (IE) is a critical component of the complex collaborative medication process in residential aged care facilities (RACFs). Designing information and communication technology (ICT) to support complex processes requires a profound understanding of the IE that underpins their execution. There is little existing research that investigates the complexity of IE in RACFs and its impact on ICT design. The aim of this study was thus to undertake an in-depth exploration of the IE process involved in medication management to identify its implications for the design of ICT. The study was undertaken at a large metropolitan facility in NSW, Australia. A total of three focus groups, eleven interviews and two observation sessions were conducted between July to August 2010. Process modelling was undertaken by translating the qualitative data via in-depth iterative inductive analysis. The findings highlight the complexity and collaborative nature of IE in RACF medication management. These models emphasize the need to: a) deal with temporal complexity; b) rely on an interdependent set of coordinative artefacts; and c) use synchronous communication channels for coordination. Taken together these are crucial aspects of the IE process in RACF medication management that need to be catered for when designing ICT in this critical area. This study provides important new evidence of the advantages of viewing process as a part of a system rather than as segregated tasks as a means of identifying the latent requirements for ICT design and that is able to support complex collaborative processes like medication management in RACFs. © 2012 IEEE.

Medication errors in residential aged care facilities: A distributed cognition analysis of the information exchange process

Background Medication safety is a pressing concern for residential aged care facilities (RACFs). Retrospective studies in RACF settings identify inadequate communication between RACFs, doctors, hospitals and community pharmacies as the major cause of medication errors. Existing literature offers limited insight about the gaps in the existing information exchange process that may lead to medication errors. The aim of this research was to explicate the cognitive distribution that underlies RACF medication ordering and delivery to identify gaps in medication-related information exchange which lead to medication errors in RACFs. Methods The study was undertaken in three RACFs in Sydney, Australia. Data were generated through ethnographic field work over a period of five months (May–September 2011). Triangulated analysis of data primarily focused on examining the transformation and exchange of information between different media across the process. Results The findings of this study highlight the extensive scope and intense nature of information exchange in RACF medication ordering and delivery. Rather than attributing error to individual care providers, the explication of distributed cognition processes enabled the identification of gaps in three information exchange dimensions which potentially contribute to the occurrence of medication errors namely: (1) design of medication charts which complicates order processing and record keeping (2) lack of coordination mechanisms between participants which results in misalignment of local practices (3) reliance on restricted communication bandwidth channels mainly telephone and fax which complicates the information processing requirements. The study demonstrates how the identification of these gaps enhances understanding of medication errors in RACFs. Conclusions Application of the theoretical lens of distributed cognition can assist in enhancing our understanding of medication errors in RACFs through identification of gaps in information exchange. Understanding the dynamics of the cognitive process can inform the design of interventions to manage errors and improve residents’ safety.

Proton translocation coupled to electron transfer reactions in terminal oxidases

Terminal oxidases are the final proteins of the respiratory chain in eukaryotes and some bacteria. They catalyze most of the biological oxygen consumption on Earth done by aerobic organisms. During the catalytic reaction terminal oxidases reduce dioxygen to water and use the energy released in this process to maintain the electrochemical proton gradient by functioning as a redox-driven proton pump. This membrane gradient of protons is extremely important for cells as it is used for many cellular processes, such as transportation of substrates and ATP synthesis. Even though the structures of several terminal oxidases are known, they are not sufficient in themselves to explain the molecular mechanism of proton pumping. In this work we have applied a complex approach using a variety of different techniques to address the properties and the mechanism of proton translocation by the terminal oxidases. The combination of direct measurements of pH changes during catalytic turnover, time-resolved potentiometric electrometry and optical spectroscopy, made it possible to obtain valuable information about various aspects of oxidase functioning. We compared oxygen binding properties of terminal oxidases from the distinct heme-copper (CcO) and cytochrome bd families and found that cytochrome bd has a high affinity for oxygen, which is 3 orders of magnitude higher than that of CcO. Interestingly, the difference between CcO and cytochrome bd is not only in higher affinity of the latter to oxygen, but also in the way that each of these enzymes traps oxygen during catalysis. CcO traps oxygen kinetically - the molecule of bound dioxygen is rapidly reduced before it can dissociate. Alternatively, cytochrome bd employs an alternative mechanism of oxygen trapping - part of the redox energy is invested into tight oxygen binding, and the price paid for this is the lack of proton pumping. A single cycle of oxygen reduction to water is characterized by translocation of four protons across the membrane. Our results make it possible to assign the pumping steps to discrete transitions of the catalytic cycle and indicate that during in vivo turnover of the oxidase these four protons are transferred, one at a time, during the P→F, F→OH, Oh→Eh, and Eh→R transitions. At the same time, each individual proton translocation step in the catalytic cycle is not just a single reaction catalyzed by CcO, but rather a complicated sequence of interdependent electron and proton transfers. We assume that each single proton translocation cycle of CcO is assured by internal proton transfer from the conserved Glu-278 to an as yet unidentified pump site above the hemes. Delivery of a proton to the pump site serves as a driving reaction that forces the proton translocation cycle to continue.