Molecular determinants for drug-receptor interactions Part 14. X-ray molecular structure and theoretical conformational (MNDO, MM2) studies of the narcotic dualist buprenorphine hydrochloride

The X-ray molecular structure of buprenorphine hydrochloride [(C₂₉H₄₂O₄N)⁺Cl⁻] was determined. The molecule forms colourless tetragonal crystals; the space group is P4₁2₁2₁ with eight molecules per unit cell of dimensions a = 11.507(2) Å and c = 41.952(9) Å. The structure was determined by direct methods and refined by the full-matrix least-squares procedure to R = 0.056 for 2251 observed reflections. The protonated buprenorphine (BPNH⁺) in the solid state adopts the T-shape form typical of benzomorphan compounds; the substituent group at the N atom is in the equatorial configuration and the cyclopropylmethyl side-chain is almost perpendicular to the piperidine ring. Theoretical studies of the conformations and the rotational energetics of BPNH⁺ were performed using both the semiquantitative MNDO and the force field (MM2) methods. The latter method predicted four low energy conformations about the N-C(21) and C(21)-C(22) bonds. Two of these were more significantly populated (59% and 30%). They may easily interconvert through only a single torsional process. The less-populated (30%) conformation was consistent with that adopted in the solid state. The MNDO method predicted different low energy conformations of the N-cyclopropylmethyl moiety. Neither method reproduced the favoured torsional angles adopted by the structurally analogous naltrexone molecule which has the opposite pharmacological profile.     

Dynamical models for state-vector reduction: do they ensure that measurements have outcomes?

Some recent criticisms of a proposed dynamical reduction theory are considered and are proved to be not cogent. By considering the visual perception process, it is made plausible that, at least at the perceptive level, the conditions required by the above-mentioned theory for dynamical reduction to occur are verified. This does not imply the attribution of a specific role to the act of conscious perception in the reduction process.     

A test of particle emission scenarios: Strange particle ratios

We show that a hadron gas model with continuous particle emission instead of freeze-out may solve some of the problems that one encounters in the latter case when studying strange particle ratios such as those by WA85.     

Regio and diastereoselective lactonisation of enolisable 1,3-dicarbonyls by reaction with mesoionic 1,3-oxazolium-5-olates

The one-pot reaction of enolisable 1,3-dicarbonyls and N-methyl-1,3-oxazolium-5-olate derivatives provided enol lactones directly in good yield and with excellent regio- and diastereocontrol.     

Structure Investigation of Bridgehead Aziridine: Synthesis,Theoretical, and Crystallographic Study of 2,4,6‐Triphenyl‐1,3‐diazabicyclo[3.1.0]hex‐3‐ene

A one‐pot three‐component procedure to efficiently create the 1,3‐diazabicyclo[3.1.0]hex‐3‐ene system is reported. The molecular structure of 2,4,6‐triphenyl‐1,3‐diazabicyclo[3.1.0]hex‐3‐ene ( 3 ) was studied by X‐ray diffraction and compared to ab initio and density‐functional‐theory (DFT) calculations restricted to the core moiety. Geometry optimizations for structural isomers and tautomeric forms of this aziridine fragment, taken as simplified models, were carried out at high calculation levels. Moreover, the same methods were utilized to evaluate the proton affinity of two crucial aziridine tautomers.     

Mathematical Modeling of Drug Release from Microemulsions: Theory in Comparison with Experiments

The topic of this paper is the study of the drug release from a drug-loaded microemulsion by reverting to a new mathematical model overcoming some drawbacks of previously proposed models. In particular, attention is focused on the mathematical expression of the drug fluxes existing between the oil and water phases during drug release. Indeed, not only the drug release kinetics, but also the drug oil-water partition coefficient strongly depend on these fluxes. Two microemulsion are considered: the first is composed by water, Tween80 as surfactant, and Triacetin as oil phase, while the second is composed by water, Tween80 as surfactant, and a Triacetin-benzylic alcohol mixture (1 : 1) as oil phase. Both of them are loaded by Nimesulide, an oil-soluble drug of considerable industrial relevance. The drug release is performed by resorting to a permeation experiment (Franz cells apparatus) as it demonstrated to be the most reliable methodology. The good agreement between the experimental permeation data and the model best-fitting ensures that the most important phenomena ruling this kind of drug release were properly accounted for by the new proposed model. Copyright 2000 Academic Press.     

Synthesis of (+)-(3S,7S,10S)- and (+)-(3S,7S,10R)-3,7,10-trimethylboratrane. Amplification of enantiomeric purity in the reacti

The synthesis is described of the two enantiomerically pure isomers (+)-(3S,7S,10S)- and (+)-(3S,7S,10R)-3,7,10-trimethylboratr The structures were determined by ¹H- and ¹³C-NMR spectroscopy. A method for increasing the enantiomeric purity by trimerization reactions of partially-resolved (S) propylene oxide is proposed. The reaction was studied from the kinetic viewpoint and interpreted according to a binomial probability scheme. The experimental findings point to a rapid growth in enantiomeric purity for the (SSS) trimer compared with the starting material, whilst no increase was found for the (SSR) trimer.