Numerical-Analytic Methods for Differential-Algebraic Systems

The numerical-analytic method is useful to show that a differential equation with a boundary condition has a solution. In this paper we use this method to differential-algebraic systems with boundary conditions. Some existence results are formulated under assumptions that the corresponding functions satisfy Lipschitz conditions in matrix notation.     

Excited-State Proton Transfer in Hydroxynaphthaldehydes Covalently Bound to Proteins

The kinetics and equilibrium of excited-state proton transfer (ESPT) in 2-hydroxynaphthaldehyde-1 (HNA-2.1) bound to proteins (bovine serum albumin, cytochrome c, and lysozyme) by an alkylamino bond was studied by means of fluorimetric steady-state and time-resolved methods. The results were compared to analogous data for 1-hydroxy naphthaldehyde-4 (HNA-1.4) bound to proteins and for other 2-naphthol derivatives bound to proteins by a sulfonamide bond, Conclusions concerning the influence on ESPT of the mode of binding and of intramolecular hydrogen bonds occurring in the case of HNA-2. 1 were drawn. An intramolecular hydrogen bond enhances the rate of ESPT but the molecular environment in the protein leads to an opposite effect by increasing reorganization energy during proton transfer. The results obtained prove that the mode of binding and the kind of group linking fluorophores to proteins influence considerably the rate and mechanism of ESPT. In naphthol groups bound to proteins by an alkylamino bond, proton dissociation depends strongly on the molecular environment in the macromolecule. This is due to the short length of the alkylamino bridge and its small interaction with electronic orbitals of the aromatic system. Fluorophores bound to proteins by a sulfonamide bond show a higher rate of ESPT, which is due partly to the electron withdrawing effect of the linking arm. The efficiency of ESPT for naphthol groups bound to proteins by a sulfonamide bond is, in most cases, sufficient for acidification of the medium and influence of the proton gradient in biological membranes.     

Method of moments approach and coupled cluster theory

Summary The single reference coupled cluster (CC) approach to the many-electron correlation problem is examined from the viewpoint of the method of moments (MM). This yields generally an inconsistent (overcomplete) set of equations for cluster amplitudes, which can be solved either in the least squares sense or by selective projection process restricting the number of equations to that of the unknowns. These resulting generalized MM-CC equations always contain the standard CC equations as a special case. Since, in the MM-CC formalism, the Schrödinger equation will be approximately satisfied on a subspace spanned by non-canonical configurations, this procedure may be helpful in extending the standard single reference CC theory to quasi-degenerate situations. To examine the potential usefulness of this idea, we explore the linear version of the CC approach for systems with a quasi-degenerate reference, in which case the standard linear theory is plagued with singularities due to the intruder states. Implications of this analysis for the structure of the wavefunction are also briefly discussed.Killam Research Fellow 1987–89     

Intershell nl4f electron correlation effects

The pair correlation energies for some nl4f pairs of the ground state of the Yb atom are calculated for the first time. The partial wave (PW ) increments to the second-order pair energies are generated using numerical first-order radial pair functions obtained as the solution of two-dimensional differential equations. The analysis of the PW s contributions shows the dominant role of the df, fg, and gh PW s for the 4d4f pair, of the pf and dg PW s for the 4p4f and 5p4f pairs, and of the sf and pg PW s for the 4s4f, 5s4f, and 6s4f pairs. A discussion of the similarities and differences of the structure of the correlation energy found in this paper with those calculated earlier for smaller atoms is given.     

Synthesis of asymmetric halomesylate mustards with aziridineethanol/alkali metal halides: application to an improved synthesis of the hypoxia prodrug PR-104

Aromatic asymmetric halomesylate mustards are efficiently prepared by reaction of activated aromatic chlorides with aziridineethanol/alkali metal halides, followed by mesylation of the haloalcohol. The reaction conditions are sufficiently mild to be compatible with a range of different substituents and protecting groups, including carboxylate and phosphate esters, and have been used in an improved synthesis of the anticancer bromomesylate mustard PR-104, now in clinical trials.     

COMPARISON OF THE SPECTROSCOPIC PROPERTIES OF 4'-AMINO PHENYLALANINE AS AN UNPROTECTED AMINO ACID AND AS A RESIDUE IN PEPTIDES

Abstract— Ultraviolet absorption and fluorescence spectra of 4'-amino phenylalanine (Aphe) and of some peptides and esters containing Aphe, are characterized. Based on these results, the applicability of Aphe for fluorescence structural investigations of peptides is evaluated. The use of Aphe as an acceptor in fluorescence energy transfer measurements offers the possibility of facilitating the determination of donor fluorescence quantum yield (φ_D) in the absence of energy transfer which usually turns out to be difficult in systems containing donor and acceptor moities. The Aphe residue in peptides also allows a better insight into intramolecular interactions.     

Principle and applications of the protein-purification-parameter screening system

For the purification of a target protein, liquid chromatography is the method of choice, if its activity has to be maintained. The selection of optimum parameters will improve in proportion to the number of individual parameters varied in initial experiments. Here a fast screening method is described, which utilizes automated parallel chromatographic experiments in the batch mode in 96-well plates. The principle of this protein-purification-parameter screening (PPS) system is demonstrated with a mixture of four proteins. An application of PPS for the determination of a purification step of an angiotensin-II-generating enzyme from a crude tissue extract is shown.     

Development and intercalibration of ultraviolet solar actinometers

Ultraviolet (UV) sunlight actinometers were developed based on the photolysis of nitrate and nitrite. Photon exposures ( i.e. time-integrated irradiances) were quantified from the photochemical production of salicylic acid (SA) or p -hydroxybenzoic acid (pHBA) formed by the reaction of the hydroxyl radical with benzoic acid. The solar response bandwidth for the nitrate actinometer in quartz tubing was 322 ± 11 nm during the Spring of 1999, while the response bandwidth of the Mylar D-filtered nitrite actinometer was 355 ± 25 nm. Intercomparisons of the nitrate and nitrite actinometers with a Smithsonian Environmental Research Center SR-18 scanning UV-B radiometer (SERC SR-18) and an Optronics OL-754 spectroradiometer (OL-754) were performed during the summer of 1998, and the winter and spring of 1999. Photon exposures determined by the nitrate actinometer were in excellent agreement with the SERC SR-18, with a slope (95% confidence interval [CI]) of 0.98 ± 0.01 based on SA production and 0.94 ± 0.02 based on pHBA production. Excellent agreement was also found between the nitrite actinometer and the OL-754, with a slope (95% CI) of 1.00 ± 0.01 using SA production and 1.00 ± 0.02 using pHBA production. These actinometers are well suited for use in the water column and are sufficiently sensitive to determine photon exposures below the 0.1% UV light-level.     

Activation of 3-amino-1,2,4-benzotriazine 1,4-dioxide antitumor agents to oxidizing species following their one-electron reduction

The mechanism by which a benzotriazine 1,4-dioxide class of anticancer drugs produce oxidizing radicals following their one-electron reduction has been investigated using tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide, 1) and its 6-methoxy (6), 7-dimethylamino (7), and 8-methyl (8) analogues. By measuring the changes in absorption with pH, we found that the radical anions undergo protonation with radical pK(r) values of 6.19 +/- 0.05, 6.10 +/- 0.03, 6.45 +/- 0.04, and 6.60 +/- 0.04, respectively. The one-electron reduced species underwent a first-order reaction, with increased rate constants from 112 +/- 23 s(-)(1) for 1 to 777 +/- 12 s(-)(1)(6), 1120 +/- 29 s(-)(1) (7), and 825 +/- 89 s(-)(1) (8) at pH 7. No overall change in conductance was observed following the one-electron reduction of 6, and 8 at pH 4.5, consistent with the protonation of the radical anions, but a loss in conductance was seen for one-electron reduced 7 because of further protonation of the initially formed radical. This is assigned to the protonation of the dimethylamino group of the radical species, which has a pK(a) of 8.8 +/- 0.3. All conductance changes take place on a time-scale shorter than those of the above first-order reactions, which are not associated with the formation or loss of charged species. The absorption spectra present at the end of the unimolecular reactions were found to be similar to those formed immediately upon the one-electron oxidation of the respective substituted 3-amino-1,2,4-benzotriazine 1-oxides, and it is suggested that common benzotriazinyl radicals are formed by both routes. All these intermediate radicals underwent dismutation to produce final spectra matched by equal contributions of the parent compound and their respective substituted 3-amino-1,2,4-benzotriazine 1-oxides. By establishing redox equilibria between the intermediate radicals formed on the one-electron oxidation of the respective 3-amino-1,2,4-benzotriazine 1-oxides of the compounds and reference compounds, we found the one-electron reduction potential of the oxidizing radicals to range from 0.94 to 1.31 V. The benzotriazinyl radical of tirapazamine was found to oxidize dGMP and 2-deoxyribose with rate constants of (1.4 +/- 0.2) x 10(8) M(-)(1) s(-)(1) and (3.7 +/- 0.5) x 10(6) M(-)(1) s(-)(1), respectively.     

Role of Time Scales in the Coupled Epidemic-Opinion Dynamics on Multiplex Networks

Modelling the epidemic’s spread on multiplex networks, considering complex human behaviours, has recently gained the attention of many scientists. In this work, we study the interplay between epidemic spreading and opinion dynamics on multiplex networks. An agent in the epidemic layer could remain in one of five distinct states, resulting in the SIRQD model. The agent’s attitude towards respecting the restrictions of the pandemic plays a crucial role in its prevalence. In our model, the agent’s point of view could be altered by either conformism mechanism, social pressure, or independent actions. As the underlying opinion model, we leverage the q-voter model. The entire system constitutes a coupled opinion–dynamic model where two distinct processes occur. The question arises of how to properly align these dynamics, i.e., whether they should possess equal or disparate timescales. This paper highlights the impact of different timescales of opinion dynamics on epidemic spreading, focusing on the time and the infection’s peak.