Biomedical subjects
Publications and source records attributed to Josef Michl.
For future use in self-assembly of surface structures, the adsorption on the surface of mercury of a series of tetraphenylcyclobutadienecyclopentadienylcobalt double-decker sandwich complexes with five mercury and sulfur containing "tentacles" on the cyclopentadienyl deck has been examined by combined electrochemical and Langmuir trough techniques.
We discuss possible improvements in the efficiency of dye-sensitized photovoltaic cells using dyes capable of singlet fission into two triplets, thus producing two electron-hole pairs from a single photon. It is pointed out that, in addition to derivatives of large alternant hydrocarbons, those of biradicals are also likely candidates for a favorable ordering of excited-state energy levels, E(T2), E(S1) > 2E(T1). A large number of potentially favorable structures has been examined by the semiempirical Pariser-Parr-Pople method and some also by the time-dependent density functional theory method. Several likely candidates have been identified for experimental examination.
The geometries of 35 conformers of Me(SiMe2)nMe (n = 4, 1; n = 5, 2; n = 6, 3; n = 7, 4) were optimized at the MP2/VTDZ level, and CCSD(T) single-point calculations were done at three MP2/VTDZ conformer geometries of 1. The relative ground-state energies of the conformers of 1-4 in the gas phase were obtained from the MP2/VTDZ electronic energy, zero-point vibrational energy, and thermal corrections at 0, 77, and 298 K. Relative energies in an alkane solvent at 77 and 298 K were obtained by the addition of solvation energies, obtained from the SM5.42R model. The calculated energies of 26 of the conformers (n = 4-6) have been least-squares fitted to a set of 15 additive increments associated with each Si-Si bond conformation and each pair of adjacent bond conformations, with mean deviations of 0.06-0.20 kcal/mol. An even better fit for the energies of 24 conformers (mean deviations, 0.01-0.09 kcal/mol) has been obtained with a larger set of 19 increments, which also contained contributions from selected combinations of conformations of three adjacent bonds. The utility of the additive increments for the prediction of relative conformer energies in the gas phase and in solution has been tested on the remaining nine conformers (n = 6, 7). With the improved increment set, the average deviation from the SM5.42R//MP2 results for solvated conformers at 298 K was 0.18 kcal/mol, and the maximum error was 0.98 kcal/mol.
PNC-28 is a p53 peptide from its mdm-2-binding domain (residues 17-26), which contains the penetratin sequence enabling cell penetration on its carboxyl terminal end. We have found that this peptide induces necrosis, but not apoptosis, of a variety of human tumor cell lines, including several with homozygous deletion of p53, and a ras-transformed rat acinar pancreatic carcinoma cell line, BMRPA1. Tuc3. On the other hand, PNC-28 has no effect on untransformed cells, such as rat pancreatic acinar cells, BMRPA1, and human breast epithelial cells and no effect on the differentiation of human stem cells. In this study, we now test PNC-28 in vivo for its ability to block the growth of BMRPA1. Tuc3 cells. When administered over a 2-week period in the peritoneal cavities of nude mice containing simultaneously transplanted tumors, PNC-28 causes complete destruction of these tumors. When delivered concurrently with tumor explantation at a remote site, PNC-28 causes a complete blockade of any tumor growth during its 2-week period of administration and 2 weeks posttreatment, followed by weak tumor growth that plateaus at low tumor sizes compared with tumor growth in the presence of a control peptide. When administered after tumor growth has occurred at a site remote from the tumor, PNC-28 causes a decrease in tumor size followed by a slow increase in tumor growth that is significantly slower than growth in the presence of control peptide. These results suggest that PNC-28 may be effective in treating cancers especially if delivered directly to the tumor.
In prior studies, we have found that oncogenic ras-p21 protein induces oocyte maturation using pathways that differ from those activated by insulin-induced wild-type ras-p21. Both oncogenic and wild-type ras-p21 require interactions with raf, but unlike oncogenic ras-p21, insulin-activated wild-type ras-p21 does not depend completely on activation of MEK and MAP kinase (MAPK or ERK) on the raf kinase pathway. To determine what raf-dependent but MAPK-independent pathway is activated by wild-type ras-p21, we have analyzed gene expression in oocytes induced to mature either with oncogenic ras-p21 or with insulin using a newly available Xenopus gene array. We find a number of proteins that are preferentially expressed in one or the other system. Of these, two proteins, both dual function kinases, T-Cell Origin Protein Kinase (TOPK) and the nuclear kinase, DYRK1A, are preferentially expressed in the insulin system. Confirming this finding, blots of lysates of oocytes, induced to mature with oncogenic ras-p21 and insulin, with anti-TOPK and anti-DYRK1A show much higher protein expression in the lysates from the insulin-matured oocytes. Neither of these kinases activates or is activated by MAPK and is therefore an attractive candidate for being on a signal transduction pathway that is unique to insulin-activated wild-type ras-p21-induced oocyte maturation.
In pentane solution, 2 equiv of the icosahedral CB(11)Me(12)(*) radical cleaves the Si-Si bond of hexaalkyldisilanes by boron to silicon methyl transfer with formation of 2 equiv of methyltrialkylsilanes. The loss of a methyl radical converts the CB(11)Me(12)(*) radical into an internally charge-compensated "boronium ylide" CB(11)Me(11) with a naked vertex, which can be formally viewed as a deprotonated hypercloso carborane. It has been isolated as an air-sensitive solid, stable only below approximately -60 degrees C. The naked vertex appears to be in position 12 since the material reacts instantaneously with alcohols and ethers to form the 12-alkoxy anions 12-CB(11)Me(11)OR. It reacts with many other nucleophiles to yield more complex mixtures containing similar products. DFT calculations for the four CB(11)Me(11) isomers give closed-shell ground-state electronic structures. For the isomer with naked vertex 12, a DFT computational search failed to reveal any skeletal dimers, apparently due to excessive methyl-methyl repulsions, and only a cyclic dimer bound through weak interactions of one of the 7-methyl hydrogen atoms on each cage with the empty exocyclic orbitals on B12 of the other cage was found. Natural hybrid orbital populations suggest that the three possible isomers of monomeric boronium ylides are close to true singlet ylides, with triplet states approximately 50 kcal/mol higher. The calculated electronic structure of the carbonium ylide is close to a singlet carbene, with a triplet state approximately 16 kcal/mol higher. An attempted preparation of Me(3)C(+)CB(11)Me(12)(-) yielded neopentane and products consistent with a sequential loss of methyl groups from the carborane cage with a transient formation of similar boronium ylides. Probable mechanisms of these methyl transfer reactions are considered, and the possibly quite general role of "ylide" structures in Lewis acid induced substitution reactions on the boron vertices of carboranes and boranes is noted.
We report an easy access to the salts of the LiC(BMe)11- anion, which greatly simplifies the synthesis of compounds carrying the -C(BMe)11- substituent, including the title anions. The previously recognized and puzzling spontaneous oligomerization of the solid lithium salts CH2=CH(CH2)(n-2)C(BMe)11- Li+ upon storage under ambient conditions is now shown to proceed by a radical mechanism, with the "naked" Li+ cation acting as a catalyst. The degree of polymerization is higher in solution, especially when azoisobutyronitrile (AIBN) is used as initiator (up to approximately 50). Initiation by the thermal decomposition of AIBN is also catalyzed by naked Li+, and this initiator is effective at room temperature. Di-tert-butyl peroxide and UV irradiation can also be used. The observation of Li+ catalysis agrees with a prior prediction from ab initio calculations, according to which Li+ complexation of ethylene strongly lowers the activation energy for methyl radical addition. The results bear on the current discussion of the possible sensitivity of radical clocks to their molecular environment and suggest that naked Li+ will catalyze the radical polymerization of simple terminal alkenes.
Solutions of Li+ salts of highly alkylated derivatives of the monocarbadodecaborate anion in 1,2-dichloroethane catalyze the radical polymerization of simple terminal alkenes, dienes, and alkynes under ambient conditions, initiated by azoisobutyronitrile, di-tert-butyl peroxide, or atmospheric air.
Angular distributions of electrons scattered elastically and inelastically from cold solid molecular films of ethylene and nitrogen in various proportions, grown from the gas phase at different temperatures, have been studied by high-resolution electron energy loss spectroscopy. The probing depth of dipole and impact scattering has been investigated by covering the sample by overlayers of argon of increasing thickness. The angular distribution measured for elastically and inelastically dipole-scattered electrons was found to be peaked about the specular direction for all surface conditions studied, while a diffuse angular distribution was possible for electrons that underwent dipole-forbidden scattering. These results allow us to identify favorable conditions for monitoring the composition of a solid sample during the course of reactions occurring under exposure to low-energy electrons.
[reaction: see text] We report the synthesis of cis-endo-bicyclo[1.1.1]pentane-1,2,3,4-tetracarboxylic acid and several of its derivatives with differentiated bridgehead and bridge positions, starting with tetracyclo[3.2.0.0(1,6).0(2,6)]heptane.
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One-electron reduction of the "extended viologen" dication 1 yields the red cation radical 2, characterized by strong near-IR absorption. It has been generated and studied by pulse radiolytic, electrochemical, redox titration, UV-visible, and electron paramagnetic resonance spectroscopic methods. All results are in agreement with a fully delocalized electronic structure for 2.
Molecular dynamics simulations of the response to oscillating electric field elicited from an altitudinal dipolar molecular rotor mounted on the Au(111) surface and previously studied experimentally in static fields show unidirectional rotation in one of the three pairs of conformational enantiomers. The simulations are based on the universal force field and take into account electronic friction in the metal through its effect on the image charges. The rotor consists of two cobalt sandwich posts whose upper decks carry a biphenyl-like rotator with a dipole moment perpendicular to the rotation axle, mounted parallel to the surface. A phase diagram of rotor performance at 10 K as a function of field frequency and amplitude contains five unidirectional rotation regions: synchronous, half-synchronous (every other cycle skipped), quarter-synchronous (only indistinctly), asynchronous, and essentially no response. The nature of the subharmonic "single-molecule parametric oscillator" behavior is understood in mechanistic detail. Simulations at higher temperatures distinguish the thermal ("Brownian") and driven regimes of rotation, elucidated in terms of time-dependent potential energy surfaces for the rotation.
[structure: see text] A self-assembly path toward prismatic molecular rotors based on transversely reactive terminally metalated molecular rods and pyridine-terminated star connectors has been extended. The concept has been tested on the assembly of trigonal and tetragonal prisms from the biphenyl rod, [Ph2P(CH2)3PPh2]Pt+ -C6H4-C6H4-Pt+ [Ph2P(CH2)3PPh2], and the star-shaped connectors, 1,3,5-tris(4-ethynylpyridyl)benzene and [tetrakis(4-pyridyl)cyclobutadiene]cyclopentadienylcobalt, respectively. The prisms have been fully characterized by NMR and MS, including diffusion-ordered NMR and collision-induced dissociation, and their chiral structures optimized by molecular mechanics are discussed.
We report the synthesis and spectral characterization of the first five members of an oligomeric series built from alternating p-connected 1,4-benzene and 1,4-pyridinium rings, 1[n]-4[n], n=1-5, with p-phenylene-bis-4,4'-(1-aryl-2,6-diphenylpyridinium) ("extended viologen") as the repeating unit. The lengths of these rodlike molecules range from 2 to 9 nm. The monomer was obtained from p-phenylene-bis-4,4'-(2,6-diphenylpyrylium) (5) and p-phenylenediamine (6) or p-aminoacetanilide (9). Higher oligomers were synthesized by stepwise elaboration of the monomer by reactions with the appropriate bis-pyrylium (5) or pyrylium-phenylene-pyridinium (8) salts. Eight different counterions were used, and dodecamethylcarba-closo-dodecaborate was found to offer particularly favorable solubility characteristics. Ultraviolet absorption spectra of the oligomers suggest that the individual extended viologen segments interact only weakly, as a result of the strongly twisted orientation of the benzene rings that separate them. The UV spectrum of the monomer was interpreted by comparison with semiempirical INDO/S calculations performed at a DFT optimized geometry.
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In the presence of a strong base, benzal chloride (C(6)H(5)CHCl(2)) and its p-substituted derivatives react with [nido-B(11)H(14)](-) to yield [closo-1-p-X-C(6)H(4)-CB(11)H(11)](-) (X = H, F, Cl, Br, I, Ph), presumably by insertion of an arylhalocarbene and oxidation. On a 1-g scale, the yields are 30-40%, except in the case of p-iodobenzal chloride, which yields only 12% of the insertion product.