Electronic couplings and on-site energies for hole transfer in DNA: systematic quantum mechanical/molecular dynamic study

The electron hole transfer (HT) properties of DNA are substantially affected by thermal fluctuations of the π stack structure. Depending on the mutual position of neighboring nucleobases, electronic coupling V may change by several orders of magnitude. In the present paper, we report the results of systematic QM/molecular dynamic (MD) calculations of the electronic couplings and on-site energies for the hole transfer. Based on 15 ns MD trajectories for several DNA oligomers, we calculate the average coupling squares 〈 V2 〉 and the energies of basepair triplets X G+ Y and X A+ Y, where X, Y=G, A, T, and C. For each of the 32 systems, 15 000 conformations separated by 1 ps are considered. The three-state generalized Mulliken-Hush method is used to derive electronic couplings for HT between neighboring basepairs. The adiabatic energies and dipole moment matrix elements are computed within the INDO/S method. We compare the rms values of V with the couplings estimated for the idealized B -DNA structure and show that in several important cases the couplings calculated for the idealized B -DNA structure are considerably underestimated. The rms values for intrastrand couplings G-G, A-A, G-A, and A-G are found to be similar, ∼0.07 eV, while the interstrand couplings are quite different. The energies of hole states G+ and A+ in the stack depend on the nature of the neighboring pairs. The X G+ Y are by 0.5 eV more stable than X A+ Y. The thermal fluctuations of the DNA structure facilitate the HT process from guanine to adenine. The tabulated couplings and on-site energies can be used as reference parameters in theoretical and computational studies of HT processes in DNA

Estimation of electronic coupling in π -stacked donor-bridge-acceptor systems: correction of the two-state model

Comparison of donor-acceptor electronic couplings calculated within two-state and three-state models suggests that the two-state treatment can provide unreliable estimates of Vda because of neglecting the multistate effects. We show that in most cases accurate values of the electronic coupling in a π stack, where donor and acceptor are separated by a bridging unit, can be obtained as Ṽ da = (E2 - E1) μ12 Rda + (2 E3 - E1 - E2) 2 μ13 μ23 Rda2, where E1, E2, and E3 are adiabatic energies of the ground, charge-transfer, and bridge states, respectively, μij is the transition dipole moments between the states i and j, and Rda is the distance between the planes of donor and acceptor. In this expression based on the generalized Mulliken-Hush approach, the first term corresponds to the coupling derived within a two-state model, whereas the second term is the superexchange correction accounting for the bridge effect. The formula is extended to bridges consisting of several subunits. The influence of the donor-acceptor energy mismatch on the excess charge distribution, adiabatic dipole and transition moments, and electronic couplings is examined. A diagnostic is developed to determine whether the two-state approach can be applied. Based on numerical results, we showed that the superexchange correction considerably improves estimates of the donor-acceptor coupling derived within a two-state approach. In most cases when the two-state scheme fails, the formula gives reliable results which are in good agreement (within 5%) with the data of the three-state generalized Mulliken-Hush model

Estimates of electronic coupling for excess electron transfer in DNA

Electronic coupling Vda is one of the key parameters that determine the rate of charge transfer through DNA. While there have been several computational studies of Vda for hole transfer, estimates of electronic couplings for excess electron transfer (ET) in DNA remain unavailable. In the paper, an efficient strategy is established for calculating the ET matrix elements between base pairs in a π stack. Two approaches are considered. First, we employ the diabatic-state (DS) method in which donor and acceptor are represented with radical anions of the canonical base pairs adenine-thymine (AT) and guanine-cytosine (GC). In this approach, similar values of Vda are obtained with the standard 6-31 G* and extended 6-31++ G* basis sets. Second, the electronic couplings are derived from lowest unoccupied molecular orbitals (LUMOs) of neutral systems by using the generalized Mulliken-Hush or fragment charge methods. Because the radical-anion states of AT and GC are well reproduced by LUMOs of the neutral base pairs calculated without diffuse functions, the estimated values of Vda are in good agreement with the couplings obtained for radical-anion states using the DS method. However, when the calculation of a neutral stack is carried out with diffuse functions, LUMOs of the system exhibit the dipole-bound character and cannot be used for estimating electronic couplings. Our calculations suggest that the ET matrix elements Vda for models containing intrastrand thymine and cytosine bases are essentially larger than the couplings in complexes with interstrand pyrimidine bases. The matrix elements for excess electron transfer are found to be considerably smaller than the corresponding values for hole transfer and to be very responsive to structural changes in a DNA stack

Electronic and vibrational contributions to first hyperpolarizability of donor-acceptor-substituted azobenzene

In this study we report on the electronic and vibrational (hyper)polarizabilities of donor–acceptorsubstituted azobenzene. It is observed that both electronic and vibrational contributions to the electric dipole first hyperpolarizability of investigated photoactive molecule substantially depend on the conformation. The contributions to the nuclear relaxation first hyperpolarizability are found to be quite important in the case of two considered isomers (cis and trans). Although the double-harmonic term is found to be the largest in terms of magnitude, it is shown that the total value of the nuclear relaxation contribution to vibrational first hyperpolarizability is a result of subtle interplay of higher-order contributions. As a part of the study, we also assess the performance of long-range-corrected density functional theory in determining vibrational contributions to electric dipole (hyper)polarizabilities. In most cases, the applied long-range-corrected exchange correlation potentials amend the drawbacks of their conventional counterparts

Analysis of chemical bonding and aromaticity from electronic delocalization descriptors

Interactions between electrons determine the structure and properties of matter from molecules to solids. Therefore, the understanding of the electronic structure of molecules will enable us to extract relevant chemical information. In the first part of this thesis, we focus our attention on the analysis of chemical bonding by means of the Electron Localization Function (ELF) and the Domain-Averaged Fermi Hole analysis (DAFH). In the second part, we assess the performance of some indicators of aromaticity by analyzing their advantages and drawbacks. We propose a series of tests based on well-known aromaticity trends that can be applied to evaluate the aromaticity of current and future indicators of aromaticity in both organic and inorganic species. Moreover, we investigate the nature of electron delocalization in both aromatic and antiaromatic systems in the light of Hückel’s (4n + 2) rule. Finally, we analyze the phenomenon of multiple aromaticity in all-metal clusters.

Development, implementation and application of electronic structural descriptors to the analysis of the chemical bonding, aromaticity and chemical reactivity

En la literatura sobre mecànica quàntica és freqüent trobar descriptors basats en la densitat de parells o la densitat electrònica, amb un èxit divers segons les aplicacions que atenyin. Per tal de que tingui sentit químic un descriptor ha de donar la definició d'un àtom en una molècula, o ésser capaç d'identificar regions de l'espai molecular associades amb algun concepte químic (com pot ser un parell solitari o zona d'enllaç, entre d'altres). En aquesta línia, s'han proposat diversos esquemes de partició: la teoria d'àtoms en molècules (AIM), la funció de localització electrònica (ELF), les cel·les de Voroni, els àtoms de Hirshfeld, els àtoms difusos, etc. L'objectiu d'aquesta tesi és explorar descriptors de la densitat basats en particions de l'espai molecular del tipus AIM, ELF o àtoms difusos, analitzar els descriptors existents amb diferents nivells de teoria, proposar nous descriptors d'aromaticitat, així com estudiar l'habilitat de totes aquestes eines per discernir entre diferents mecanismes de reacció.

Case based reasoning as an extension of fault dictionary methods for linear electronic analog circuits diagnosis

El test de circuits és una fase del procés de producció que cada vegada pren més importància quan es desenvolupa un nou producte. Les tècniques de test i diagnosi per a circuits digitals han estat desenvolupades i automatitzades amb èxit, mentre que aquest no és encara el cas dels circuits analògics. D'entre tots els mètodes proposats per diagnosticar circuits analògics els més utilitzats són els diccionaris de falles. En aquesta tesi se'n descriuen alguns, tot analitzant-ne els seus avantatges i inconvenients. Durant aquests últims anys, les tècniques d'Intel·ligència Artificial han esdevingut un dels camps de recerca més importants per a la diagnosi de falles. Aquesta tesi desenvolupa dues d'aquestes tècniques per tal de cobrir algunes de les mancances que presenten els diccionaris de falles. La primera proposta es basa en construir un sistema fuzzy com a eina per identificar. Els resultats obtinguts son força bons, ja que s'aconsegueix localitzar la falla en un elevat tant percent dels casos. Per altra banda, el percentatge d'encerts no és prou bo quan a més a més s'intenta esbrinar la desviació. Com que els diccionaris de falles es poden veure com una aproximació simplificada al Raonament Basat en Casos (CBR), la segona proposta fa una extensió dels diccionaris de falles cap a un sistema CBR. El propòsit no és donar una solució general del problema sinó contribuir amb una nova metodologia. Aquesta consisteix en millorar la diagnosis dels diccionaris de falles mitjançant l'addició i l'adaptació dels nous casos per tal d'esdevenir un sistema de Raonament Basat en Casos. Es descriu l'estructura de la base de casos així com les tasques d'extracció, de reutilització, de revisió i de retenció, fent èmfasi al procés d'aprenentatge. En el transcurs del text s'utilitzen diversos circuits per mostrar exemples dels mètodes de test descrits, però en particular el filtre biquadràtic és l'utilitzat per provar les metodologies plantejades, ja que és un dels benchmarks proposats en el context dels circuits analògics. Les falles considerades son paramètriques, permanents, independents i simples, encara que la metodologia pot ser fàcilment extrapolable per a la diagnosi de falles múltiples i catastròfiques. El mètode es centra en el test dels components passius, encara que també es podria extendre per a falles en els actius.

What it takes: Issues in implementing electronic portfolios

The purpose of this study was to investigate the issues in implementing electronic portfolios as a school-wide innovation, and to provide a resource guide for the future use of electronic portfolios at Central Institute for the Deaf.

Electronic structure of point defects in controlled self-doping of the TiO2 (110) surface: Combined photoemission spectroscopy and density functional theory study

Point defects in metal oxides such as TiO2 are key to their applications in numerous technologies. The investigation of thermally induced nonstoichiometry in TiO2 is complicated by the difficulties in preparing and determining a desired degree of nonstoichiometry. We study controlled self-doping of TiO2 by adsorption of 1/8 and 1/16 monolayer Ti at the (110) surface using a combination of experimental and computational approaches to unravel the details of the adsorption process and the oxidation state of Ti. Upon adsorption of Ti, x-ray and ultraviolet photoemission spectroscopy (XPS and UPS) show formation of reduced Ti. Comparison of pure density functional theory (DFT) with experiment shows that pure DFT provides an inconsistent description of the electronic structure. To surmount this difficulty, we apply DFT corrected for on-site Coulomb interaction (DFT+U) to describe reduced Ti ions. The optimal value of U is 3 eV, determined from comparison of the computed Ti 3d electronic density of states with the UPS data. DFT+U and UPS show the appearance of a Ti 3d adsorbate-induced state at 1.3 eV above the valence band and 1.0 eV below the conduction band. The computations show that the adsorbed Ti atom is oxidized to Ti2+ and a fivefold coordinated surface Ti atom is reduced to Ti3+, while the remaining electron is distributed among other surface Ti atoms. The UPS data are best fitted with reduced Ti2+ and Ti3+ ions. These results demonstrate that the complexity of doped metal oxides is best understood with a combination of experiment and appropriate computations.

The effects of electronic prescribing on the quality of prescribing

Aims To investigate the effects of electronic prescribing (EP) on prescribing quality, as indicated by prescribing errors and pharmacists' clinical interventions, in a UK hospital. Methods Prescribing errors and pharmacists' interventions were recorded by the ward pharmacist during a 4 week period both pre- and post-EP, with a second check by the principal investigator. The percentage of new medication orders with a prescribing error and/or pharmacist's intervention was calculated for each study period. Results Following the introduction of EP, there was a significant reduction in both pharmacists' interventions and prescribing errors. Interventions reduced from 73 (3.0% of all medication orders) to 45 (1.9%) (95% confidence interval (CI) for the absolute reduction 0.2, 2.0%), and errors from 94 (3.8%) to 48 (2.0%) (95% CI 0.9, 2.7%). Ten EP-specific prescribing errors were identified. Only 52% of pharmacists' interventions related to a prescribing error pre-EP, and 60% post-EP; only 40% and 56% of prescribing errors resulted in an intervention pre- and post-EP, respectively. Conclusions EP improved the quality of prescribing by reducing both prescribing errors and pharmacists' clinical interventions. Prescribers and pharmacists need to be aware of new types of error with EP, so that they can best target their activities to reduce clinical risk. Pharmacists may need to change the way they work to complement, rather than duplicate, the benefits of EP.

The impact of a closed-loop electronic prescribing and administration system on prescribing errors, administration errors and staff time: a before-and-after study

Objectives: To assess the impact of a closed-loop electronic prescribing, automated dispensing, barcode patient identification and electronic medication administration record (EMAR) system on prescribing and administration errors, confirmation of patient identity before administration, and staff time. Design, setting and participants: Before-and-after study in a surgical ward of a teaching hospital, involving patients and staff of that ward. Intervention: Closed-loop electronic prescribing, automated dispensing, barcode patient identification and EMAR system. Main outcome measures: Percentage of new medication orders with a prescribing error, percentage of doses with medication administration errors (MAEs) and percentage given without checking patient identity. Time spent prescribing and providing a ward pharmacy service. Nursing time on medication tasks. Results: Prescribing errors were identified in 3.8% of 2450 medication orders pre-intervention and 2.0% of 2353 orders afterwards (p<0.001; χ2 test). MAEs occurred in 7.0% of 1473 non-intravenous doses pre-intervention and 4.3% of 1139 afterwards (p = 0.005; χ2 test). Patient identity was not checked for 82.6% of 1344 doses pre-intervention and 18.9% of 1291 afterwards (p<0.001; χ2 test). Medical staff required 15 s to prescribe a regular inpatient drug pre-intervention and 39 s afterwards (p = 0.03; t test). Time spent providing a ward pharmacy service increased from 68 min to 98 min each weekday (p = 0.001; t test); 22% of drug charts were unavailable pre-intervention. Time per drug administration round decreased from 50 min to 40 min (p = 0.006; t test); nursing time on medication tasks outside of drug rounds increased from 21.1% to 28.7% (p = 0.006; χ2 test). Conclusions: A closed-loop electronic prescribing, dispensing and barcode patient identification system reduced prescribing errors and MAEs, and increased confirmation of patient identity before administration. Time spent on medication-related tasks increased.