Electronic structure of nitric oxide adducts of bis(diaryl-1,2-dithiolene)iron compounds: four-membered electron-transfer series [Fe(NO)(L)2]z (z = 1+, 0, 1-, 2-)

Four members of the electron-transfer series [Fe(NO)(S(2)C(2)R(2))2]z (z = 1+, 0, 1-, 2-) have been isolated as solid materials (R = p-tolyl): [1a](BF4), [1a]0, [Co(Cp)2][1a], and [Co(Cp)2]2[1a]. In addition, complexes [2a]0 (R = 4,4-diphenyl), [3a]0 (R = p-methoxyphenyl), [Et(4)N][4a] (R = phenyl), and [PPh(4)][5a] (R = -CN) have been synthesized and the members of each of their electron-transfer series electrochemically generated in CH(2)Cl(2) solution. All species have been characterized electro- and magnetochemically. Their electronic, M?ssbauer, and electron paramagnetic resonance spectra as well as their infrared spectra have been recorded in order to elucidate the electronic structure of each member of the electron-transfer series. It is shown that the monocationic, neutral, and monoanionic species possess an {FeNO}6 (S = 0) moiety where the redox chemistry is sulfur ligand-based, (L)2-(L*)1-: [Fe(NO)(L*)2]+ (S = 0), [Fe(NO)(L*)(L)]0 <--> [Fe(NO)(L)(L*)]0 (S = 1/2), [Fe(NO)(L)2]- (S = 0). Further one-electron reduction generates a dianion with an {FeNO}7 (S = 1/2) unit and two fully reduced, diamagnetic dianions L2-: [Fe(NO)(L)2]2- (S = 1/2).     

A rationally designed macrocyclic cavitand that kills bacteria with high efficacy and good selectivity

An amphiphilic macrocyclic cavitand that shows good antibacterial activity, comparable to that of peptide-based antibiotics was developed by rational design and its antibacterial selectivity over mammalian cells was examined.     

Copper(II) cyclam-based complexes for radiopharmaceutical applications: synthesis and structural analysis

Two molecular structures of the copper(II) complex, Cu(H(2)TETA), have been determined by X-ray crystallography. The Jahn-Teller distortion differs between the two structures; occurring either along the axis of the pendant acetate arms or across the macrocyclic ring. An analysis of deposited data from over one hundred copper(II) cyclam X-ray structures in the Cambridge Structural Database (CSD) reveals that Jahn-Teller distortion across the ring is highly unusual for such compounds in the solid state. Novel chelators based on the piperazino/side-bridged cyclam have been prepared and copper(II) complexes formed. The single crystal X-ray structures of two copper(II) complexes, with either an ester or acid N-pendant arm, have been determined and in both cases the pendant arm is bound to the metal centre.     

Lessons in molecular recognition. 2. Assessing and improving cross-docking accuracy

Docking methods are used to predict the manner in which a ligand binds to a protein receptor. Many studies have assessed the success rate of programs in self-docking tests, whereby a ligand is docked into the protein structure from which it was extracted. Cross-docking, or using a protein structure from a complex containing a different ligand, provides a more realistic assessment of a docking program's ability to reproduce X-ray results. In this work, cross-docking was performed with CDocker, Fred, and Rocs using multiple X-ray structures for eight proteins (two kinases, one nuclear hormone receptor, one serine protease, two metalloproteases, and two phosphodiesterases). While average cross-docking accuracy is not encouraging, it is shown that using the protein structure from the complex that contains the bound ligand most similar to the docked ligand increases docking accuracy for all methods ("similarity selection"). Identifying the most successful protein conformer ("best selection") and similarity selection substantially reduce the difference between self-docking and average cross-docking accuracy. We identify universal predictors of docking accuracy (i.e., showing consistent behavior across most protein-method combinations), and show that models for predicting docking accuracy built using these parameters can be used to select the most appropriate docking method.     

Parallel DFT gradients using the Fourier Transform Coulomb method

The recently described Fourier Transform Coulomb (FTC) algorithm for fast and accurate calculation of Density Functional Theory (DFT) gradients (Füsti-Molnar, J Chem Phys 2003, 119, 11080) has been parallelized. We present several calculations showing the speed and accuracy of our new parallel FTC gradient code, comparing its performance with our standard DFT code. For that part of the total derivative Coulomb potential that can be evaluated in plane wave space, the current parallel FTC gradient algorithm is up to 200 times faster in total than our classical all-integral algorithm, depending on the system size and basis set, with essentially no loss in accuracy. Proposed modifications should further improve the overall performance relative to the classical algorithm.     

Dual functional, polymeric self-assembled monolayers as a facile platform for construction of patterns of biomolecules

We report a facile approach to the construction of patterns of biomolecules based on polymeric self-assembled monolayers (pSAMs) that possess dual functions: "bio-reactive (post-functionalizable)" and "bio-inert (anti-biofouling)" properties. To prepare pSAMs on Si/SiO2 wafers were synthesized new random copolymers by radical polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA), 3-(trimethoxysilyl)propyl methacrylate (TMSMA), and N-acryloxysuccinimide (NAS), and referred to as poly(TMSMA-r-PEGMA-r-NAS). Poly(TMSMA-r-PEGMA-r-NAS) was designed to play triple roles: "surface-reactive", "bio-reactive", and "bio-inert" ones. The pSAMs of poly(TMSMA-r-PEGMA-r-NAS) were formed on Si/SiO2 wafers with 1 h incubation of the substrates in the polymer solution, which showed approximately a 1 nm-thick film as measured by ellipsometry. After the formation of the pSAMs, the feasibility of the pSAMs as a dual functional surface (bio-inert and bio-reactive properties) was examined. The ability of the pSAMs to block nonspecific adsorption of proteins was evaluated against bovine serum albumin as a model protein. High-resolution N(1s) X-ray photoelectron spectroscopy (XPS) analysis on the protein adsorption revealed that significant reduction up to approximately 97% was observed compared to the unmodified Si/SiO2 wafer. In addition, micropatterns of streptavidin with high signal-to-noise ratios were achieved using microcontact printing (microCP) of NH2-bearing biotin onto the pSAMs of poly(TMSMA-r-PEGMA-r-NAS) on glass slides, which suggests that other biomolecules could also be efficiently immobilized onto the pSAMs with high specificity while minimizing nonspecific adsorption. On the other hand, the surface density of both bio-reactive and anti-biofouling functionality could be tailored by simply changing initial feed ratios of each monomer in the polymer synthesis: different molar ratios of the bio-reactive group (NAS: 33%, 20%, and 10%, respectively) were employed. When micropatterns of streptavidin were constructed, the pSAMs with 33% NAS moiety showed the highest immobilization of the protein. Taken together, the present dual functional, random copolymers may have warrant applications in the field of biosensors and biochips.     

Rapidly reversible hydrophobization: an approach to high first-pass drug extraction

We have investigated a rapidly reversible hydrophobization of therapeutic agents for improving first-pass uptake in locoregional drug therapy. This approach involves the attachment of a hydrophobic moiety to the drug by highly labile chemical linkages that rapidly hydrolyze upon injection. Hydrophobization drastically enhances cell-membrane association of the prodrug and, consequently, drug uptake, while the rapid lability protects nontargeted tissues from exposure to the highly active agent. Using the membrane-impermeable DNA intercalator propidium iodide, and melphalan, we report results from in vitro cellular internalization and toxicity studies. Additionally, we report in vivo results after a single liver arterial bolus injection, demonstrating both tumor targeting and increased survival in a mouse tumor model.     

A new arithmetic for linear free radical copolymerization

As a consequence of their method of production, polymer chains are polydisperse in size, composition and sequence distribution. In this work we present a new method of uniquely identifying these “polymer isomers” termed “Digital Encoding of Polymeric Chains”. The method involves replacing distinguishable features of the chain such as monomer units, branches, etc. with a number. This unique sequence of numbers provides a digital code, which, depending on the base of the arithmetic used (binary, ternary) can be translated into a unique decimal equivalent number. We have applied this technique to the case of binary copolymerization in a CSTR at steady state and show how the sequence spectra of the chain populations are conveniently obtained. Furthermore, the technique shows that rich information about the copolymerization kinetics, reactivity ratios and termination mode can be obtained from analysis of the short chains of the distribution. The implications for this in parameter estimation and controlled polymerization are discussed in this paper.     

Syn and anti aryl nitrenium ions

Calculations at several levels of ab initio molecular orbital theory have been carried out on 20 polycyclic aryl nitrenium ions of general structure ArNH⁺ and containing from two to four condensed rings. Electronic interactions between the aryl ring and the NH⁺ group stabilize all ions relative to PhNH⁺ by amounts varying from 14 to 40 kcal mol⁻¹ depending on the ring system and on the site of substitution. Apart from a few symmetrical cases, the ions exist in distinct syn and anti configurations, separated by substantial inversion barriers. At the HF/6‐31G(d) level, the latter are predicted to lie in the rather narrow range of 27.8±2.0 kcal mol⁻¹. Simple PMO analyses are presented based on the analogy with odd alternant hydrocarbon cations. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 231–243, 1999