Noninvasive conventional imaging methods are established technologies in modern drug discovery and development providing valuable morphological, physiological, and metabolic information to characterize disease phenotypes, to evaluate the efficacy of therapy and to identify and develop potential biomarkers for clinical drug evaluation. The development of target-specific or molecular imaging has added a new dimension: molecular events such as the target expression, the drug–target interaction, or the activation of signal transduction pathways can be studied in the intact organism with high spatial and temporal resolution. Molecular imaging is inherently a multimodality approach. In this article, we review the role of molecular imaging for drug discovery and development focusing on nonnuclear imaging methods, i.e., magnetic resonance imaging (MRI) and optical imaging techniques based on fluorescence and bioluminescence readouts. Examples discussed are direct visualization of target expression using target-specific ligands or reporter genes, pathway imaging, and cell-trafficking studies.
Calculated molecular electronicproperties of 20 recently reported cyclic peroxy ketals have been rationalized with their in vitro antimalarial activity with the overall goal to guide the design for safer and effective peroxide-containing antimalarial agents. Stereoelectronicproperties were calculated on the optimized geometry of each compound using the ab initio 3-21G* quantum chemical basis set. Potency appears to be related to electronic properties rather than structural properties such as bond lengths and bond angles though an aliphatic cyclic ring seems to be a structural requirement for potent activity. Electronic properties such as differences in molecular polarity, in electrostatic potential profiles about the peroxide bond and the aromatic ring, in peroxide bond strength, and in the LUMO orbital energy of the molecules are all associated with potency. The three-dimensionalisopotential profile beyondthe van der Waals surface at −10 kcal/mol for the more potent analogs has a distinct large negative potential region by the aromatic ring extending to the methoxy moiety, suggesting a site for initial recognition interaction with the receptor away from the peroxide bond. The HOMO and LUMO isodensity surfaces for all molecules are located on the aromatic ring. The peroxide bond strength of the compounds is around 100 kcal/mol greater than the peroxide-containing clinically used antimalarial artemisinin compounds. In addition, density of the peroxy ketals also appears related to potent activity. The above features of the cyclic peroxy ketals are consistent with these compounds being less potent than the artemisinin compounds, but at the same time are less likely to be as neurotoxic as the artemisinins.
In the course of the present work CaF2 epitaxialfilms were grown on Si(111) substrates by means ofMBE. The Si substrates were chemically cleaned priorto insertion into the system. The final volatile oxidewas desorbed in situ by heating to 850Ĉ. CaF2 was evaporated from aKnudsen-type cell by use of a graphite crucible, whilethe growth temperature was held at 650 Ĉ.RHEED (Reflection High Energy Electron Diffraction)has been used to monitor the film growth in situand to study the epitaxial quality. Also we have usedthe MeV He+ RBS channeling technique to look atdefects and to measure strain in the CaF2 layer.Usually good crystallographic properties are achievedunder optimum growth conditions, with values ofχmin < 5%. Electrical properties aremeasured by use of a special MIS structure.
The charge transfer complex (CTC)tetrathiafulvalene-9-dicyanomethylene-2,4,5,7-tetranitrofluorene(DT 4 NF) displays a degree of charge transfer Z = 0.7.This value is situated close to the border between intermediateand strong CTC's. Under the view, that CTC's with values 0.4 <Z < 0.7 in general are molecular electrical conductors, fourdifferent CTC's were prepared formed of tetrathiafulvalene andacceptors which were derived from9-dicyanomethylene-2,4,5,7-tetranitrofluorene (DT 4 NF) withsubstituents of less electronegative capacity. The degree of chargetransfer was determined by use of IR- and Raman spectroscopy.It was found, that its value decreased in all the studied cases. Inparticular, for the complex with the acceptor 9-dicyanomethylene-4,5,7-trinitrofluorene-2-carboxylic acid(DC2TNF), Z was found within the limits representative ofmolecular electrical conductors. This result is explained by thefact, that the nitro substituent of the 2-position fluorene skeletonwas exchanged by a group of similar volume (carboxyl), but withless electron-withdrawing effect.
We report quantum mechanical computations and experimental evidence which suggest that the backbone conformation of globular proteins depends generally on the conservation of that part of the hydrogen bond network or ribbon which is joined, in general, directly to the backbone and is largely independent of the remainder of this whole network of hydrogen bonds. The familiar hydrogen bonds of the α helix and the β sheet form about one-half of this ribbon of hydrogen bonds. Both water molecules and hydrogen bonding side chain groups are involved in the formation of the ribbon.This view of the three-dimensional structure of globular proteins in terms of the `molecule' allows us to deal with the non-secondary structure as well as with the familiar secondary structure. It also suggests that the ribbon contains approximately the same number of hydrogen bonds within all three structures – the α helix, the β sheet and the coil – and that this is the reason for the ease of interconversion of these three structures.
CaF 2 epitaxial layers were prepared by MBE and investigated by RBS and ion channeling measurements. Films of about 30 nm thickness were found to be strained by tensile stress causing a rhombohedral symmetry of the layers. These results are interpreted in terms of the different thermal expansion coefficients of substrate and deposit, respectively.
The chemical properties of beta zeolite are interconnected with its structure in a complicated way. In general terms, the strength of the acid sites in the beta phase depends strongly on its structure, topology and composition. The quantum chemical calculations of the beta zeolite cluster model have been carried out in order to predict how the cluster's local structure influences the geometric parameters and thus affects the chemical functionality of the beta zeolite. Computer simulations of a beta zeolite model with one lattice aluminium, or boron, or titanium or vanadium ions and of its acidic centres have been carried out. The acidity of the framework oxygen atoms in the vicinity of the lattice atom centre has been calculated and compared. The reactivity of catalytic species comprisingthe lattice ion and a hydroperoxo ligand has been studied as an oxidising site.
The charge transfer in charge transfer complexes, based on Zinc-naphtholimines (Zn[RNAFIN]2) with TCNQ is studied in the present paper. New electronic states form with the effect of corresponding transition bands in vibrational spectra. This proves the existence of mixed valence complexes. Band peak shifts in the visible spectral region are manifest, which provide for the evaluation of the charge transfer (CT). In this work the CT is calculated by use of the C≡N stretch band shift.Due to this results, we prove that an increase of the ligand volume of the donor (RNAFIN) abates the degree of charge transfer.
tructural properties and intermediate range order insodium-alumino silicate glasses of general formulaeNa 2 OċxAl 2 O 3 ċ(3-x)SiO 2 have beeninvestigated at different concentrations ofAl 2 O 3 by means of molecular dynamicssimulations. The influence on the calculatedstructural parameters of the initial randomnessexpressed by the starting structure has been analysedand discussed. The results obtained support the hypothesis that acontinuous transition between two limiting structuresis responsible for the anomalous variation in thediffusion properties observed between 5and 10% of Al 2 O 3 addition.
The paper reports Monte Carlo and molecular dynamicsresults for pure liquid dimethyl sulfoxide (DMSO) at298 K and 1 atm. The classical 6–12 Lennard–Jones plusCoulomb pairwise potential was used to calculateintermolecular interaction energy. Potentialparameters for the liquid were optimized in this work.Some thermodynamic and dynamical properties obtained,such as heat of vaporization, density and diffusioncoefficient, are in good agreement with theexperimental values. The present model is comparedwith other models for DMSO reported previously. It isshown to be an improvement over earlier potentials.The structure factors and the radial distributionfunctions (rdf), are compared with experimentalresults for the liquid. The analysis shows that thestructure of DMSO is not completely understood yet anddeserves deeper investigation. The geometry of thedimer that corresponds to the rdf plots obtained, isreported. The results suggest that the dipole momentof this dimer plays an important role in the structureof the liquid.
Magnetic interactions in the three copper(II)-complex polymers, [Cu(PZ)(NO 3 ) 2 ] n , [Cu(PM)(NO 3 ) 2 (H 2 O) 2 ] n , and [Cu(PM) 2 (NO 3 ) 2 ] n are discussed on the basis of extended Hückel calculations inthe formulas PZ and PM stand for pyrazine and pyrimidine, respectively. Interactions between the Cu-3d orbitals and the σ lone-pair orbitals of pyrazine and pyrimidine are analyzed from the viewpoint of `through-space' and `through-bond' interactions using binuclear complexes to model the three copper(II) polymers. Three conclusions can be drawn from the orbital interaction analysis: (1) in the first polymer, a superexchange pathway is formed with the σ bond of Cu–-N and the through-bond interaction between the lone pairs of the nitrogen atoms of pyrazine will lead to an antiferromagnet state; (2) in the second polymer a superexchange pathway is formed with the σ bond of Cu–-N and the through-space interaction between the lone pairs of the nitrogen atoms of pyrimidine, and as a result an antiferromagnetic state will be preferred; and (3) in the third polymer., there is no effective pathway in respect of overlap interaction and the HOMO and the LUMO are actually degenerate, and thus a ferromagnetic state will arise. The band structures are analyzed to characterize the magnetic properties of the antiferromagnetic polymers, [Cu(PZ)(NO 3 ) 2 ] n and [Cu(PM)(NO 3 ) 2 (H 2 O) 2 ], and the ferromagnetic polymer, [Cu(PM) 2 (NO 3 ) 2 ] n .
Photochromic and thermochromicanus have been encapsulated in an organic-inorganichybrid network, produced by theSol-Gel method. It was found that the photochromic anils have been transformed to thermochromic, something observed for the first time in rigid glasses. Spectroscopic investigations indicate a common infrastructure responsible for the coloured xerogel.
Single crystalline Si(111) samples were alloyedby a bombardment of both 60 and 200 keV energetic Ge+ ions. The implantation dose was variedbetween 1014 and 1017 cm-2. Rutherford backscattering and channeling analysis was applied in order to study the formation of a single crystalline Si–Ge alloy layer, both prior and after a thermal treatment at a temperature of 900 Ĉ. Thethickness and the depth of the implanted layer, as well as their composition and crystalline quality was determined, and it was found that a single crystalline Si–Ge alloy layer was created, with both depth and composition depending on the ion energy and the ion dose.
Computational techniques have become important tools in the preliminary stages of the design of new molecules. The mutual arrangements of interacting molecular parts and the required accessibility of important reactive groups on the peripheral regions of possible new molecules can be tested by computational means before the expensive and often complex synthetic methods are used to the actual construction of these molecules. There are some common features involved in the computational representation of molecular fragments and the synthetic methodologies used in the process of incorporating actual molecular fragments in such “engineered” molecules. One trend that appears to link these two approaches is based on the following observation: the greater local “autonomy” is shown by the calculated electron density contribution of a given molecular fragment, the more likely that this fragment can be regarded as a suitable building block of the molecule, and it is also more likely that there are convenient synthetic methods for the “delivery” of this fragment to its desired “target” location in the new molecule to be synthesized. For a precise formulation of this statement, a new concept, the “degree of molecular fragment autonomy” is introduced, using the inherent properties of molecular electron densities.
Selective recognition in the title compound, (C14H14FeO3)2 ċ (C10H8N2), between ferrocenyl carbonyl propanoic acid and 4,4'-bipyridine through strong O–-HċN intermolecular hydrogen bonds results in a novel supramolecular architecture. Its crystal structure has been solved by single-crystal X-ray diffraction methods while its characterization has been studied by IR and DSC.
General expressions for the tangential and radial forces for two current elements moving contra-wise to each other in a helical manner are derived. The two repulsive forces are calculated as a function of velocity, with explicit values given for parameters, appropriate to DNA. The calculated electrodynamic respulsive forces oppose the stabilizing standard radial and tangential forces in the helix and, if large enough, can result in strand separation. The currents required are of the same order of magnitude as observed intra-cellular currents and as passed recently through short segments of duplex DNA. A speculative mechanism involving a resistance-capacitance membrane network in series with a resistance DNA network is formulated. Strand separation in DNA may well originate in such an electrodynamic system.
1,3- bis-[4-(N-aza-15-crown-5)-benzylidene]cyclopentanone-2 ( I), a ketocyanine dye, was synthesized. The electronic absorption and emission spectra, protolytic interactions in aqueous alcohol media and complex formation with alkali earth metals in acetonitrile were studied for the dye ( I) and for several model compounds. It was shown that protonation of both dialkylamino groups of all compounds studied takes place at closely similar pH values. The complexation of alkali earth metals with azacrown derivative ( I) takes place at azacrown moieties and the carbonyl group. The sequence of binding to these sites is different for Mg 2+ and Ba 2+ ions. The effective ejection of Ba 2+ ion out of the azacrown cycle was observed in the excited state, though, as in the case of Mg 2+ ion, such process occurred only partially. The results obtained suggest that this azacrown derivative of dibenzylidene cyclopentanone is sensitive to alkali earth ions and has prospects for different biologically oriented applications.
Di-anil of 2-hydroxy-5-methyl-isophthaldehyde was investigated for thermochromic and photochromic properties in the solid state. The compound has been found to exhibit remarkable thermochromic behavior, due to its structural characteristics, with strong contribution of the quinoid form in the ground state at room temperature.
