Development of an internal searching algorithm for parameterization of the MM2/MM3 force fields

Application of Allinger's MM2/MM3 force fields to molecules of real interest is frequently hindered by the lack of parameters for various heterocyclic systems and for poly-functionalized molecules. A common approach to this problem is to manually choose missing parameters “by analogy” with those that are part of the force field's internal parameter set. Naturally, this is generally attempted only by those possessing extensive experience with force fields. In order to use the MM2/MM3 force fields to study herbicides, an algorithm has been developed to automate this process for the non MM2 specialist. Using a set of “relative cost” criteria for atom type replacement, the algorithm searches the force field parameter set and selects the most appropriate parameters for a given molecule whose MM2 output file contains “missing parameter” errors. The program selects parameter error messages from a standard MM2 output file, finds analogous parameters, asks the user to verify their appropriateness and creates a standard MM2 parameter deck for the molecule of interest.     

The cleavage of 2,5-dihydro-2-furanylcarbene

Atomic carbon reacts with 2,5-dihydrofuran to effect deoxygenation and by C-H insertion to give 2,5-dihydro-2-furanylcarbene which subsequently cleaves to two molecules of acetylene and formaldehyde.     

In vitro metabolite identification using fast gradient high performance liquid chromatography combined with tandem mass spectrometry.

Metabolite identification can provide critical information for further synthesis during the lead optimization stage of drug discovery. Fast chromatographic gradient methodology was explored to reduce the analysis time for metabolite identification by liquid chromatography/tandem mass spectrometry while maintaining chromatographic separation of all components of interest. Short HPLC columns (2 cm) containing 3 microm particles were used and the chromatographic conditions involved elevated flow rates (1.0-2.5 mL/min) and fast, full range linear gradients (<2 min). Detection was accomplished by fast scanning triple quadrupole mass spectrometers or a quadrupole time-of-flight mass spectrometer. Analysis of liver microsomal incubations of several compounds indicates that separation of isomeric metabolites as well as the parent compound is feasible with analysis times not exceeding 2 minutes.     

Small-angle neutron scattering studies of an adsorbed non-ionic surfactant (C12E24) on hydrophobised silica particles in water

Small-angle neutron scattering (SANS) studies of aqueous dispersions of St?ber silica particles (which have been hydrophobised by having 1-octadecanol grafted to their surface), carrying an adsorbed layer of the nonionic surfactant C12E24, in water, have been performed as a function of temperature. Using mixtures of D2O and H2O, the composition of the continuous phase was adjusted to have the same scattering length density as the silica particles. Hence, only the scattering from the 1-octadecanol and C12E24 layers was detected. The data have been analyzed using both a surface Guinier analysis and a two-layer structure model. It has been found that a step profile best describes the inner combined adsorbed layer (1-octadecanol grafted chains, plus the penetrating alkyl chains from the surfactant) and a semi-Gaussian profile the extended poly(ethylene oxide) outer layer. Both analyses demonstrated that the combined surface layer contracted with increasing temperature.     

A superior polypyridine ligand for platinum(II) lumaphors. Methyl substituents with a large stereoelectronic influence

This research deals with the synthesis and characterization of a new series of platinum(II) polypyridine complexes that incorporate a relatively rigid and hydrophobic ligand. The parent complex Pt(php)Cl(+), where php denotes 2-(2'-pyridyl)-1,10-phenanthroline, resembles Pt(trpy)Cl(+), where trpy denotes 2,2':6',2'-terpyridine, but is photoluminescent in solution. Hence php derivatives should prove to be superior tags and/or spectroscopic probes for biological systems. A theoretical analysis reveals some of the advantages of php over trpy as a platform. Due to a ligand pi system with a relatively small HOMO-LUMO gap, the emission from Pt(php)Cl(+) exhibits significant vibrational structure and a mixed (3)pi-pi*/(3)d-pi* orbital parentage. In deoxygenated dichloromethane solution the php complex exhibits an emission quantum yield of 3.1 x 10(-3) and an excited-state lifetime of 0.23 micros at room temperature. However, methyl groups have an unusually strong stereoelectronic influence, particularly at the 5,6-positions of the phenanthroline moiety. The platinum(II) complex with 2-(2'-pyridyl)-3,5,6,8-tetramethyl-1,10-phenanthroline is the best emitter with an emission yield of 0.055 and a lifetime of 9.3 micros in dichloromethane. Strongly donating solvents like dimethylformamide are potent quenchers of the emission. The methods of characterization used include absorption and emission spectroscopies, electrochemistry, and, in the case of [Pt[2-(2'-pyridyl)-4,7-dimethyl-1,10-phenanthroline]Cl]O(3)SCF(3), X-ray crystallography. Another intriguing finding is that methyl substituents have preferred orientations with respect to the phenanthroline ligand.     

Biomimetic anchor for surface-initiated polymerization from metal substrates

In this paper, we demonstrate the first use of a catecholic initiator for surface-initiated polymerization (SIP) from metal surfaces to create antifouling polymer coatings. A new bifunctional initiator inspired by mussel adhesive proteins was synthesized, which strongly adsorbs to Ti and 316L stainless steel (SS) substrates, providing an anchor for surface immobilization of grafted polymers. Surface-initiated atom transfer radical polymerization (SI-ATRP) was performed through the adsorbed biomimetic initiator to polymerize methyl methacrylate macromonomers with oligo(ethylene glycol) (OEG) side chains. X-ray photoelectron spectroscopy, surface FT-IR, and contact angle analysis confirmed the sequential grafting of initiator and polymer, and ellipsometry indicated the formation of polymer coatings of up to 100 nm thickness. Cell adhesion experiments performed with 3T3-Swiss albino fibroblasts showed substantially reduced cell adhesion onto polymer grafted Ti and 316L SS substrates as compared to the unmodified metals. Moreover, micropatterning of grafted polymer coatings on Ti surfaces was demonstrated by combining SI-ATRP and molecular assembly patterning by lift-off (MAPL), creating cell-adhesive and cell-resistant regions for potential use as cell arrays. Due to the ability of catechols to bind to a large variety of inorganic surfaces, this biomimetic anchoring strategy is expected to be a highly versatile tool for polymer thin film surface modification for biomedical and other applications.     

Strukturen und Eigenschaften der Natriumperoxoborat-Hydrate

The structural features of the sodium peroxoborates are explained by combining the results of different methods of investigation. An anion ring (see “Inhaltsübersicht”) is the essential structural element of all these compounds. There exist one hexahydrate, one tetrahydrate and two modifications of the anhydrous compound Na₂[(OH)₂B(O₂)₂B(OH)₂]. Removing OH-groups from the anion ring leads to radical-like structures which are discussed. Preliminary experiments in aqueous solution indicate a hydrolysis equilibrium for the anion ring.     

Atomic force microscopy investigation of the mechanism of calcite microcrystal growth under Kitano conditions

A combined atomic force microscopy (AFM)-inverted optical microscopy technique has been used to image the surface of calcite single microcrystals, with dimensions of 10-20 microm, at high resolution. The microcrystals were grown on a glass substrate using the Kitano method, a process that involves the outgassing of carbon dioxide from a saturated solution of calcium carbonate. The resulting increase in the supersaturation of the solution, with respect to calcium carbonate, induces crystallization. It is demonstrated, for the first time, that calcite microcrystals formed in this way exhibit a single spiral growth hillock on the (104) surface, as evidenced by a spiral step pattern, indicating that growth occurs at steps arising from an individual screw dislocation. The subsequent reactivity of these crystals under Kitano conditions has been followed in situ using AFM imaging.     

Effects of organic solvents on the scission energy of rodlike micelles

The linear viscoelastic response of erucyl bis(hydroxyethyl) methylammonium chloride with added KCl has been studied as a function of temperature and nonpolar solvent addition. The plateau modulus is independent of temperature from 25 to 40 degrees C, in contrast to previous studies with salicylate counterions that showed a plateau modulus increasing with temperature over this range. The average micelle length, L, predicted by the model of Cates, depends experimentally on Escis/kBT, where Escis is the scission energy of the chain and kBT is the Boltzmann constant times the absolute temperature. With ethanol addition, the calculated average contour length, L, decreases by a factor of 4 as ethanol concentration varies from 0 to 1.3 M. This corresponds to an apparent energy for scission, Escis, decrease from 81 +/- 8 to 74 +/- 7 kJ/mol. On the other hand, only 80 mM of hexane is required to cause a decrease in Escis to the same level, and for hexane addition levels above 70 mM a disruption in the plateau modulus indicates the disruption of the rodlike structure. The correspondence between the effect of temperature and the effect of solvent addition allows the development of "solvent/temperature" superposition rules to predict the rheology of these viscoelastic fluids at elevated temperatures.     

Molecular mechanics studies of ketene derivatives and related structures

The MM2 and MM3 force fields have now been parameterized for ketene and its various derivatives. With the addition of the C_sp ? O bond stretching and C?C_sp?O bond bending parameters, calculations were performed on ketene and six substituted ketene compounds. The MM2 results are quite good with only minimal errors in the calculation of C? H bond lengths and H-C-H bond angles. Additionally, C? F bond parameters in MM2 have been re-adjusted to give better results in monofluorinated species, but, unfortunately, resulting in greater error in the polyfluorinated compounds. The results of geometry calculations by MM3 are similar to those obtained by MM2 with the exception of a significant improvement in the geometry of dimethylketene. The MM3 vibrational frequencies calculated in this study are also in good agreement with available experimental and ab initio results with the exception of a few low frequency in-and out-of-plane bending modes. © 1992 by John Wiley & Sons, Inc.