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Frank Jensen

Publications and source records attributed to Frank Jensen.

10 recordsLinked to original sources
PubMed2006

Anticancer thiopyrano[2,3-d][1,3]thiazol-2-ones with norbornane moiety. Synthesis, cytotoxicity, physico-chemical properties, and computational studies.

A series of novel 9-substituted-3,7-dithia-5-azatetracyclo[9.2.1.0(2,10).0(4,8)]tetradecen-4(8)-ones-6 have been synthesized by a stereoselective hetero-Diels-Alder reaction of 5-ylidene-4-thioxo-2-thiazolidone derivatives with norbornene-2. All the compounds have been evaluated for antitumor activity in in vitro human tumor cell lines, and 10 of them possessed significant and selective cytotoxicity (MGM logGI50 approximately -4.17 to -4.98, for individual cell lines logGI50 up to -8). COMPARE analyses of differential growth inhibition patterns of compounds at the GI50 level showed high correlations with some of the antitubulin agents. The lipophilicity of the compounds was studied by RP-TLC and found to correlate well with calculated logP values. Docking and structure-activity relationship studies produced seven QSAR models with 2 or 3 variables, with correlation coefficients r2>0.9 and leave-one-out cross-validation correlation coefficients, q2>0.8.

Antineoplastic Agents↗
PubMed2005

Controlled formation and topologies of thiophenolate-based macrocycles: rings, cylinders and bowls.

The Schiff-base condensations of 1,3-diaminopropane with a protected thiophenol dialdehyde in the presence of Ni(2+), Pd(2+) or Zn(2+) can be controlled to yield either mononuclear acyclic, or 2 + 2 and 4 + 4 macrocyclic complexes by the choice of both metal cation and counteranion. The Ni(2+) complex of the 2 + 2 macrocycle contains two square-planar nickel ions and shows an arrangement similar to one observed previously: the mu-S atoms of the thiophenolate groups are pyramidal and lie on the same side of the plane defined by the four N atoms of the macrocycle to give a V-shaped molecule. By contrast, the Zn(2+) complex of the 2 + 2 macrocycle undergoes oligomerization to yield a bowl-shaped hexanuclear complex that includes a mu(3)-carbonate anion. Essential for this topology is the presence of three mu(3)-S-thiophenolato groups that link the three macrocyclic units to form a Zn(3)S(3) ring that seals the bottom part of the bowl. In this arrangement, one of the pyramidal mu(3)-S atoms in each dinuclear Zn(2+) complex is inverted relative to the arrangement observed for the dinickel complexes. Molecular modelling suggests that inversion about the mu-S atoms of the 2 + 2 macrocyclic complexes is readily accessible at room temperature and that the contrasting arrangements observed for the Ni(2+) and Zn(2+) complexes are those energetically most favourable for the respective metal ions. Rare 4 + 4 macrocyclic complexes are isolated as neutral dinuclear complexes for Ni(2+) and Pd(2+) and as a tetranuclear complex cation for Zn(2+). The topologies of these systems contrast significantly: those with two square-planar Ni(2+) or Pd(2+) ions form extended rings, while that with Zn(2+) forms a sulfur-lined cylinder which hosts acetonitrile molecules in the crystalline state. Reaction conditions can also be optimised to produce 2 + 1 acyclic ligands as their mononuclear Ni(2+) and Pd(2+) complexes, providing potentially useful building blocks for production of more complicated macrocyclic and supramolecular systems.

Journal Article↗
PubMed2005

Squeezing the [Cu-OH...H2O-Cu]3+ bridge by cryptate encapsulation.

Treatment of cryptand L(1) with Cu(II) generates a H3O2(-)-bridged dicopper(II) cryptate, 2, where the guest anion has responded to steric constraint by a significant shortening of the O-O distance to 2.325(9) A; computational optimization at the B3LYP/6-31(d) level suggests that the bridging O-H...O H-bond is bent (approximately 157 degrees) but that the barrier to interchange of the bridging H atom is low (<4 kJ mol(-1)). This cryptate, rather than the [Cu2L(1)muCN]3+ species recently claimed to derive from cleavage of the C-C bond of the solvent, is the product of acetonitrile recrystallization of the initially formed reaction product, 1.

Journal Article↗
PubMed2005

Contracted basis sets for density functional calculations: segmented versus general contraction.

The differences between segmented and general contracted basis sets of double and triple zeta quality are analyzed for first and second row elements. Based on coverage of the exponent space and the performance for molecular properties, it is shown that a segmented contraction requires duplication of one primitive function compared to a general contraction for double zeta type basis sets. For triple zeta basis sets, segmentation necessitates either addition of one primitive function and expanding to a quadruple valence space, or addition of two primitive functions. For molecular properties depending on the valence orbitals, such as atomization energies, equilibrium distances, and vibrational frequencies, some of the inner functions describing the core orbitals can be removed without significantly affecting the accuracy. Several of the popular basis sets in common use correspond to such core-pruned basis sets.

Journal Article↗
PubMed2004

Polarization consistent basis sets. V. The elements Si-Cl.

Polarization consistent basis sets, optimized for density functional calculations, are proposed for the elements Si-Cl. Their performance for atomization energies, equilibrium geometries, harmonic vibrational frequencies, and associated infrared intensities is compared with other commonly used basis sets. Atomization energies can be predicted to within 0.01 kJ/mol per atom of the basis set limit by extrapolation of the pc-2, -3, and -4 results. Equilibrium bond distances and harmonic vibrational frequencies can be calculated to within 10(-5) A and 0.5 cm(-1), respectively, of the basis set limit. The pc-n basis sets are shown to give comparable or better accuracy than other alternatives, while containing fewer or equal number of primitive basis functions.

Journal Article↗
PubMed2002

Electron capture dissociation of weakly bound polypeptide polycationic complexes.

We have previously reported that, in electron capture dissociation (ECD), rupture of strong intramolecular bonds in weakly bound supramolecular aggregates can proceed without dissociation of weak intermolecular bonds. This is now illustrated on a series of non-specific peptide-peptide dimers as well as specific complexes of modified glycopeptide antibiotics with their target peptide. The weak nature of bonding is substantiated by blackbody infrared dissociation, low-energy collisional excitation and force-field simulations. The results are consistent with a non-ergodic ECD cleavage mechanism.

Anti-Bacterial Agents↗
PubMed1997

Kinetic Isotope Effects and Transition State Geometries. A Theoretical Investigation of E2 Model Systems.

Ab initio calculations at the MP2/6-31+G level have been performed on E2 model systems to investigate whether differences in kinetic isotope effects correlate with changes in transition state geometries. By combining various nucleophiles (NH(2)(-), OH(-), F(-), PH(2)(-), SH(-), Cl(-)) and leaving groups (NH(3), Br(-), Cl(-), F(-), SH(-)) for reactions of the type Nu(-) + CH(3)CH(2)X, a large diversity of transition structures from reactant-like to product-like are generated. For each reaction one primary and two different alpha-secondary kinetic isotope effects are calculated. The primary kinetic isotope effects depend strongly on the nucleophilic placement in the periodic system, which mainly is due to differences in equilibrium isotope effects. When this effect is subtracted, the primary kinetic isotope effects display the expected maximum for symmetric transition structures, although the maximum is broad. The secondary kinetic isotope effects associated with the leaving group provide a qualitative correlation with the hybridization at the carbon, but the corresponding effects at the carbon where the hydrogen abstraction takes place is uncorrelated with the transition state geometry.

Journal Article↗
PubMed1996

Ring Strain Effects on the Interconversion of Intermediates in the Reaction of Organic Sulfides with Singlet Oxygen.

Ab initio methods are used to investigate ring strain effects on sulfide-singlet oxygen reaction intermediates. The optimized persulfoxide and thiadioxirane structures derived from 3-, 4-, and 5-membered ring sulfides showed minor albeit systematic changes in geometry. These persulfoxides and thiadioxiranes are best described as distorted tetrahedral and trigonal bipyramidal in nature, respectively. We find that the persulfoxy sulfur becomes less sulfonium-ion-like in character with decreasing ring size. In addition, the persulfoxide and the thiadioxirane are nearly isoenergetic in all cases and their interconversion barriers are nearly identical. We speculate that the anticipated ring strain effect in the persulfoxide is compensated for by a weaker sulfur-oxygen interaction and the corresponding relaxation of the need to attain the energetically preferred tetrahedral geometry.

Journal Article↗