Large Water-Soluble Cyclophanes with Convergent Intracavity Functionality

New tricyclic spacers, readily available through fourfold Mannich reaction of substituted dibenzyl ketones, were introduced into a series of ten H₂O-soluble cyclophanes with spacious preorganized cavity binding sites. These spacers provide H₂O-solubility with amine or crown-ether functionality remote from the cyclophane cavity while directing functional groups such as keto or OH groups in a precise geometrical array inside the cavity. The cyclophanes were designed to include organic substrates via a combination of apolar and specific polar functional group interactions. The X-ray crystal-structure analysis of the tritopic receptor 18 with one potential neutral-molecule and two cation-binding sites showed a large rectangular open cavity with dimensions of roughly 9 × 14 Å and a spacing of 9.7 Å between the O-atoms of two convergent C?O groups. Despite the binding-site preorganization, cyclophanes incorporating two of the new spacers did not show any substrate binding in aqueous solutions. The failure of these systems to function as receptors is mainly due to steric hindrance to important cyclophane aromatic ring-guest interactions. Also, the favorable solvation of the intracavity functionality may prevent the formation of complexes. Hybrid receptors constructed from the novel spacers and diphenylmethane units were found to bind flat aromatic substrates as well as bulky [4.2]paracyclophanes. The observed large differences in stability (ΔΔG°> 2 kcal mol^?1) of the complexes formed by three structurally closely related hybrid receptors with convergent C?O, OH or CH₂ groups and 6-hydroxynaphthalene-2-carbonitrile as guest can be explained by a strong solvation effect of the convergent functional groups on apolar inclusion complexation.     

Synthesis of Benzazepine Analogues of Noscapine

The synthesis of benzazepine analogues of the opium alkaloid noscapine ( 1 ) is described. The benzazepines 2 and 3 were prepared starting from nornarceine ethyl ester ( 4 ; readily available from 1 ) in several steps. X-Ray analysis of compound 2 revealed that it is not a diastereosisomer mixture but a racemate of the threo-form and thus has the same configuration as 1 .     

Synthesis of β -Cyperone via Fungal Hydroxylation of thujone-derived tricyclic cyclopropanes

Synthesis of optically active sesquiterpenes with a eudesmane C-skeleton from the chiral starting material thujone involves transformation of a tricyclic intermediate (1R,2R,4S)-1,7-dimethyl-4-(1-methylethyl)tricyclo[4.4.0.0^2,4]dec-6-en-8-one ( 2 ) into the bicyclic compound β -cyperone ( 5 ). Hydroxylation of 2 at C(5) or C(11) permits subsequent opening of the cyclopropane ring and rearrangement to β -cyperone. In this publication, studies involving hydroxylation of 2 by fungal cultures are presented. The resultant products are useful intermediates in efficient synthesis of eudesmane sesquiterpenes. Of five fungi tested, Rhizopus oryzae ATCC 11145 proved most versatile. It hydroxylates at the exocyclic C(11) position in high yield (70%) and, to a lesser extent, at C(5) (5%). Enzymatic activity appears at the end of growth phase and at least 2.2 g of 2 per liter can be metabolized without significant loss of product yield. A second fungus, Cunninghamella echinulata ATCC 9244, proved most useful for hydroxylation of derivatives of 2 for the preparation of derivatives of β -cyperone, although product yields were low (2–20%), some derivatives were nonreactive, and hydroxylation at C(9) occurred. The relationship between precursor structure and enzyme affinity is discussed.     

Energy levels of small titanium oxide clusters obtained from SCF calculations

The energy levels of small titanium oxide clusters [(TiO₂)₂, and (TiO₂H)₃, and (TiO₂H)₂] have been calculated using ab initio SCF methods. Both crystal and relaxed geometries have been considered. Systematic changes in the valencelevel structure resulting from geometry relaxation are found, which may be related to band-gap changes experimentally observed for small titanium oxide particles. In addition, a Ti? OH local surface state is found to be well described within a limited cluster model. © 1994 John Wiley & Sons, Inc.     

Publication list

The helium atom in its ground state, subject to strong magnetic fields, is treated using a variational method. Trial functions consisting of Gaussians with nonlinear parameters variationally optimized are used. The form of these functions is a generalized s-symmetry-state properly modified to admit spatial deformation along the direction on which the magnetic field is applied. © 1994 John Wiley & Sons, Inc.     

Why define atoms in real space?

The physics of a system is determined by a variation of the action integral, i.e., by a variation of the space–time volume integral of the Lagrange function. If one demands that the properties of an atom in a molecule be derived from physics, the atom must generate its own space–time volume, requiring that its boundaries be defined in real space. The variations in the action are related to the actions of generators of infinitesimal unitary transformations. In the general case, the action integral is altered by generators acting in both the spacelike and timelike surface bounding the space–time volume, whereas for a total isolated system, the physics is totally determined by their action in just the spacelike surfaces at the two time endpoints. It is shown and illustrated for a one-dimensional system that the definition of an atom corresponds to the possibility of choosing a subsystem in such a way that the contributions to the change in action resulting from the evolution in time of its spatial boundaries vanishes identically. The properties of these subsystems and of the total system of which they are a part are, therefore, determined by one and the same action principle. This choice of subsystem corresponds to the possibility of augmenting the Lagrange function by the divergence of the gradient of the electron density a step that, while leaving the equations of motion unchanged, modifies the generating operators in the required manner. © 1994 John Wiley & Sons, Inc.     

Theory of relaxed density matrices: Application to second-order response properties

The evaluation of second derivatives of the electronic energy for nonvariational wave functions using an energy functional is discussed. It is shown that, in certain cases, the formation of the first-order relaxed density matrix leads to an efficient algorithm for the calculation of second-order response properties. Detailed formulas are given for second-order Møller–Plesset perturbation theory. © 1994 John Wiley & Sons, Inc.     

Density functionals for exchange and correlation energies: Exact conditions and comparison of approximations

A set of exact conditions is compiled for the purpose of developing and testing approximations for the exchange-correlation energy as a functional of the electron density. Special emphasis is placed upon recently developed density-scaling relationships. Commonly used generalized gradient approximations are compared against several of these conditions. A direct tabular comparison of these functionals (not of calculated properties) with one another is also made. © 1994 John Wiley & Sons, Inc.