Elevated-temperature metathesis syntheses of structurally novel alkali-metal tetrakis(3,5-di-tert-butylpyrazolato)lanthanoidate(III) complexes: toluene-coordinated discrete bimetallic complexes and supramolecular chains

Sodium and potassium tetrakis(3,5-di-tert-butylpyrazolato)lanthanoidate(III) complexes [M[Ln(tBu(2)pz)(4)]] have been prepared by reaction of anhydrous lanthanoid trihalides with alkali metal 3,5-di-tert-butylpyrazolates at 200-300 degrees C, and a 1,2,4,5-tetramethylbenzene flux for M=K. On extraction with toluene (or occasionally directly from the reaction tube) the following complexes were isolated: [Na(PhMe)[Ln(tBu(2)pz)(4)]] (1 Ln; 1 Ln=1 Tb, 1 Ho, 1 Er, 1 Yb), [K(PhMe)[Ln(tBu(2)pz)(4)]].2 PhMe (2 Ln; 2 Ln=2 La, 2 Sm, 2 Tb, 2 Ho, 2 Yb, 2 Lu), [Na[Ln(tBu(2)pz)(4)]](n) (3 Ln; 3 Ln=3 La, 3 Tb, 3 Ho, 3 Er, 3 Yb), [K[Ln(tBu(2)pz)(4)]](n) (4 Ln; 4 Ln=4 La, 4 Nd, 4 Sm, 4 Tb, 4 Ho, 4 Er, 4 Yb, 4 Lu), with the last two classes generally being obtained by loss of toluene from 1 Ln or 2 Ln, and [Na(tBu(2)pzH)[Ln(tBu(2)pz)(4)]].PhMe (5 Ln; 5 Ln=5 Nd, 5 Er, 5 Yb). Extraction with 1,2-dimethoxyethane (DME) after isolation of 2 Ho yielded [K(dme)[Ho(tBu(2)pz)(4)]] (6 Ho). X-ray crystal structures of 1 Ln (=1 Tb, 1 Ho; P2(1)/c), 2 Ln (=2 La, 2 Sm, 2 Tb, 2 Yb, 2 Lu; Pnma), 3,4 Ln (=3 La, 3 Er, 4 Sm; P2(1)/m), and 5 Ln (=5 Nd, 5 Er, and 5 Yb; P1) show each group to be isomorphous regardless of the size of the Ln(3+) ion. All complexes contain eight-coordinate [Ln(eta(2)-tBu(2)pz)(4)] units. These are further linked to the alkali metal by bridging through two (1,2,5 Ln) or three (3,4 Ln) tBu(2)pz groups which show striking coordination versatility. Sodium is coordinated by an eta(4)-PhMe, a micro-eta(2):eta(2)-tBu(2)pz, and a micro-eta(4)(Na):eta(2)(Ln)-tBu(2)pz ligand in 1 Ln, and by one eta(1)-tBu(2)pzH and two micro-eta(3)(Na):eta(2)(Ln) ligands in 5 Ln. By contrast, potassium has one eta(6)-PhMe and two micro-eta(5)(K):eta(2)(Ln) ligands in 2 Ln. Classes 3,4 Ln form polymeric chains with the alkali metal bonded by two micro-eta(3)(NNC-M):eta(2)(Ln)-tBu(2)pz ligands within [MLn(tBu(2)pz)(4)] units which are joined together by eta(1)(C)-tBu(2)pz-Na, K linkages.     

Application of solid phase peptide synthesis to engineering PEO–peptide block copolymers for drug delivery

This work describes a simple, versatile solid-phase peptide-synthesis (SPPS) method for preparing micelle-forming poly(ethylene oxide)-block-peptide block copolymers for drug delivery. To demonstrate its utility, this SPPS method was used to construct two series of micelle-forming block copolymers (one of constant core-composition and variable length; the other of constant core length and variable composition). The block copolymers were then used to study in detail the effect of size and composition on micellization. The various block copolymers were prepared by a combination of SPPS for the peptide block, followed by solution–phase conjugation of the peptide block with a proprionic acid derivative of poly(ethylene oxide) (PEO) to form the PEO-b-peptide block copolymer. The composition of each block component was characterized by mass spectrometry (MALDI and ES-MS). Block copolymer compositions were characterized by ¹H NMR. All the block copolymers were found to form micelles as judged by transmission electron microscopy (TEM) and light scattering analysis. To demonstrate their potential as drug delivery systems, micelles prepared from one member of the PEO-b-peptide block copolymer series were physically loaded with the anticancer drug doxorubicin (DOX). Micelle static and dynamic stability were found to correlate strongly with micelle core length. In contrast, these same micellization properties appear to be a complex function of core composition, and no clear trends could be identified from among the set of compositionally varying, fixed length block copolymer micelles. We conclude that SPPS can be used to construct biocompatible block copolymers with well-defined core lengths and compositions, which in turn can be used to study and to tailor the behavior of block copolymer micelles.     

Synthesis, structures and spectroelectrochemistry of methyl-substituted bis(η-indenyl)iron(II) complexes

Several new methyl-substituted indenyl ferrocenes were prepared by metathesis reactions of the indenide (generated from the appropriate indene with BuLi) with ferrous chloride. The indenides used to prepare new ferrocenes were: 2-methyl-, 1,2-dimethyl-, 4,7-dimethyl-, 1,4,7-trimethyl-, and 1,3,4,7-tetramethyl-indenide. These indenyl ferrocenes, along with those prepared from indenide, 1-methylindenide, and 1,3-dimethylindenide, were then characterized by ¹H and ¹³C NMR, UV/visible spectroscopy, cyclic voltammetry and mass spectrometry. The cyclic voltammetry showed an additive relationship between oxidation potential and the number of methyl groups which is also position-dependent, whereas the UV/visible spectra showed two absorptions essentially unaffected by methyl substitution. Additionally, bis(2-methylindenyl)iron(II) and bis(4,7-dimethylindenyl)iron(II) were characterized by X-ray crystallography.     

Multisample probe for fast-atom bombardment / mass spectrometry

An inexpensive multisample fast-atom bombardment (FAB) probe assembly was designed for high-throughput analysis of samples on a VG ZAB-SE mass spectrometer. The system consists of a vacuum lock system and a FAB probe whose tip contains five or more sample wells. The probe enters the mass spectrometer source region perpendicular to the secondary ion beam axis, The probe is maintained at high voltage on contact with a spring clip attached to the screen plate of the source block. Sample throughput with the multisample probe is twice that of a coaxial probe, with about twice the sensitivity and no sample cross contamination.     

Proton ionizable crown compounds. 18. Comparison of alkali metal transport in a H2O-CH2Cl2-H2O liquid membrane system by four proton-ionizable macrocycles containing the dialkylhydrogenphosphate moiety

The macrocycle-mediated fluxes of alkali, alkaline earth, and several transition metal cations have been determined and compared in a H₂O-CH₂Cl₂-H₂O liquid membrane system using four water-insoluble macrocycles containing a dialkylhydrogenphosphate moiety. Transport of alkali metal cations by these ligands was greatest from a source phase pH = 12 or above into an acid receiving phase (pH = 1.5). Very low fluxes were observed for the transport of the alkaline earth cations and all transition metal ions studied except Ag⁺ and Pb²⁺ which were transported reasonably well by these new macrocycles.Deceased: September 5, 1987.     

The reaction of carbanions with 2-substituted-2-nitropropanes : Substitution and dimerization occurring by radical chain processes involving electron transfer

The reaction of mono-enolate anions with O₂NCMe₂X where X = Cl, NO₂, p-MePhSO₂ yield coupling (RCOCH(R′)(CMe₂NO₂) and enolate dimerization products (RCOCH(R′)CH(R′)COR) by free radical chain mechanisms involving bimolecular substitution or electron transfer reactions between the enolate anion and the intermediate nitro alkane radical anion (XCMe₂NO₂^?).     

Single and double hydrogen migration in the fragmentation of 3-methyl-2-butyl trifluoroacetate

Three of the main oxygen-containing fragments resulting from 3-methyl-2-butyl trifluoroacetate (11) had been identified previously as the 1-triflnoroacetoxyethyl cation (m/z 141, 12, product of simple cleavage), and the products of single (m/z 142) and double hydrogen transfer (m/z 143, protonated ethyl trifluoroacetate). Collisionally activated dissociation of m/z 142 and the isotopomers resulting from 11-2-d, 11-1-d₃, 11-5,6-d₆, and 11-¹⁸O₂ has established that m/z 142 is the oxygen protonated 1-trifluoroacetoxyethyl free radical (17) formed by hydrogen shift irom a γ-methyl group to oxygen in the molecular ion, rather than in a complex (18) between 12 and the 2-propyl free radical, as expected based on a mechanistic model existing in the literature. The second hydrogen transferred originates in the other γ-methyl group; its migration may occur, but does not have to, in the complex between 17 and a molecule of propene, prior to dissociation of the two fragments. Collision-activated dissociation has now shown that the m/z 140 ion observed in the spectrum is the molecular ion of vinyl trifluoroacetate, possibly formed by a hydrogen transfer from 12 to the 2-propyl radical in the complex 18. The hydrogen migration to oxygen exhibits no isotope effect, whereas the transfers to carbon atoms exhibit small primary and α secondary kinetic isotope effects. Exclusive migration of the tertiary hydrogen from C(3) occurs in the formation of 2-methylbutene cation radical (m/z 70) from the molecular ion. The hydrocarbon ion fragments and the heteroatom-containing fragments are formed from 11 by disjoint pathways.     

A genetic algorithm for the automated generation of molecules within constraints

Summary A genetic algorithm has been designed which generates molecular structures within constraints. The constraints may be any useful function, for example an enzyme active site, a pharmacophore or molecular properties from pattern recognition or rule-induction analyses. The starting point may be random or may utilise known molecules. These are modified to grow into families of structures which, using the evolutionary operators of selection, crossover and mutation evolve to better fit the constraints. The basis of the algorithm is described together with some applications in lead generation, 3D database construction and drug design. Genetic algorithms of this type may have wider applications in chemistry, for example in the design and optimisation of new polymers, materials (e.g. superconducting materials) or synthetic enzymes.     

Thermoplastic polyurethanes containing 12-hydroxymethylabietanol

Thermoplastic polyurethane elastomers incorporating the resin acid-derived 12-hydroxymethylabietanol (12-HMA) were prepared, and some physical properties are reported. A polyester macroglycol was prepared from 12-HMA, adipic acid, and ethylene glycol. This macroglycol then was combined with either poly(tetramethylene adipate) glycol (PTAd) or poly(ethylene adipate) glycol (PEAd) and 1,4-butanediol to give a glycol blend of 300 average hydroxyl equivalent weight (OHE). The glycol mixture then was combined with diphenylmethane 4,4′-diisocyanate (MDI) (NCO/OH = 1.0) to give urethane polymers soluble in tetrahydrofuran. Polymers were prepared with 0, 5, 10, 15, 20, and 25%, by weight, 12-HMA with PTAd as the other macroglycol and with 0, 10, 15, and 20% 12-HMA with PEAd as the other macroglycol. At 15% 12-HMA, polymers were made from glycol mixtures having 275 and 350 average OHE to demonstrate the effect of changing the hard-segment concentration. The presence of 12-HMA is shown to have its maximum effect on tensile properties at 15–20% in the PTAd series and at 10% in the PEAd series. In general, this effect is an increase in tensile strength and modulus and a decrease in elongation when compared with a similar polymer without the 12-HMA.