Contributions to the synthesis of some ferrocene-containing antibiotics

This Review discusses the synthesis and characterization by our Group of new antibiotics belonging to the class of penicillins, cephalosporins and rifamycins with ferrocenyl and 1, 1′-ferrocenilene residues in the molecule. As reactants for 6-aminopenicillanic acid (6-APA) and 7-aminocephalosporanic acid (7-ACA) the following were used: 1, 1-bis(chlorocarbonyl)ferrocene, ferrocenyl sulfochloride, 1, 1′-ferrocenylenedisulfochloride and thioglycolic acids S-modified with ferrocene. In the synthesis of rifamycins, the hydrazides of the thioglycolic acids, S-modified with ferrocene, were employed as nucleophilic agents. The synthesized intermediates were characterized by elemental analysis, TLC, IR, UV and ¹H NMR spectra. The characterization of new antibiotics was made by TLC, IR and UV spectral analysis. Biological activity was tested on Gram-negative and Gram-positive bacteria. Good activity is reported towards Gram-positive bacteria in the case of derivatives containing residues of thioglycolic acid S-modified with ferrocene, the antibacterial activity being similar to that of amoxicillin, carbenicillin and cephalothin. All compounds are inactive towards Gram-negative bacteria.     

Intramolecular charge transfer complexes. 16. Copolymers of N,N-dimethyl-p-aminobenzyl methacrylate with acryloyl- and methacryloyl-β-hydroxyethyl-3,5-dinitrobenzoate

A new electronodonor monomer, N,N-dimethyl-p-aminobenzyl methacrylate (DMABM), was synthesized and radical copolymerized with two electronoacceptor monomers, acryloyl- (DNBA) and methacryloyl-(DNBM) β-hydroxyethyl-3,5-dinitrobenzoate, in order to obtain intramolecular charge-transfer-complex copolymers. Also, the small-molecular models of poly(DMABM), poly(DNBA), and poly(DNBM), the respective acetates, were synthesized and used to measure the values of ionization potential I_p of the donor and the electronic affinity E_a of the acceptor. They are I_p = 7.15 eV and E_a = 1.41 eV. The lower value of I_p as compared with that of carbazole derivatives is taken as evidence of a nonterminal mechanism of copolymerization. Also, from the ¹H-NMR and electronic spectra, the intramolecular complexation is discussed in terms of total transfer of the electron from donor to acceptor structural units.     

Metallocene monomers and polymers. Ferrocenyl and ferrocenylene derivatives

The synthesis and study of some polyenes, polýiminoimides and Schiff polybases with ferrocene obtained by either polymerization or polycondensation are reported.The following monomers were used: ethynylferrocene, 1-chloro-1′-ethynyl-ferrocene, α-chloro-β-formyl-p-ferrocenylstyrene, p-ferrocenylphenylacetylene, p-ferrocenylacetophenone, 1,1′-diacetylferrocene and 1,1′-bis[β-(2-furyl)acryloyl]ferrocene which were characterized by spectral and thermodifferential analyses and Hückel MO calculations. The polymerization was performed in the presence of benzoyl and lauroyl peroxides, triisopropylboron and complex catalysts of [P(C₆H₅)₃]₂ NiX₂ type. The ferrocene derivatives were polycondensed with biuret, 4,4′-diaminodiphenyl ether, 4,4′-diaminodiphenyl thioether, 4,4′-diamino-2,2′-dinitrodiphenyl disulphide in the presence of metallic salts and p-toluene sulphonic acid as catalysts.Polymers with either linear or tridimensional structure showing good thermal stability and semiconducting properties have been obtained. Some polymers show catalytical activity in the polymerization of chloroformylated vinylic derivatives.     

Solution properties of poly[1-(9-carbazyl)-2,3-(diethoxycarbonyl)-butane-1,4-diyl]

Poly[1-(9-carbazyl)-2,3-(diethoxycarbonyl)-butane-1,4-diyl] (I), obtained by radical copolymerization of 9-vinylcarbazole with diethylfumarate, has been characterized by viscometry and light scattering. The Huggins constant in benzene at 25 is k_H = 0.33. The Mark-Houwink relationship suggests that benzene is a good solvent for the alternating copolymer I (a = 0.67; K = 1.46·10^?2 ml/g). The unperturbed dimension of the chain is given by value (R₀²/M)^0.5 = 5.73·10^?9 cm·mol^0.5 g^?0.5. The steric factor σ = 2.51 indicates a higher flexibility for this polymer than for poly[1-(9-carbazyl)ethylene].     

Highly Efficient Copper(II) Ion Sorbents Obtained by Calcium Carbonate Mineralization on Functionalized Cross‐Linked Copolymers

A new type of Cu^II ion sorbents is presented. These are obtained by CaCO₃ mineralization from supersaturated solutions on gel‐like cross‐linked polymeric beads as insoluble templates. A divinylbenzene–ethylacrylate–acrylonitrile cross‐linked copolymer functionalized with weakly acidic, basic, or amphoteric functional groups has been used, as well as different initial inorganic concentrations and addition procedures for CaCO₃ crystal growth. The morphology of the new composites was investigated by SEM and compared to that of the unmodified beads, and the polymorph content was established by X‐ray diffraction. The beads, before and after CaCO₃ mineralization, were tested as sorbents for Cu^II ions. The newly formed patterns on the bead surface after Cu^II sorption were observed by SEM, and the elemental distribution on the composites and the chemical structure of crystals after interaction with Cu^II were investigated by EDAX elemental mapping and by FTIR‐ATR spectroscopy, respectively. The sorption capacity increased significantly after CaCO₃ crystals growth on the weak anionic bead surface (up to 1041.5 mg Cu^II/g sample) compared to that of unmodified beads (491.5 mg Cu^II/g sample).     

Bioactive Polymers. XXVI. Immobilization of Pepsin on Biozan R

Pepsin was immobilized on BIOZAN R (Hercules) with dicyclohexylcarbodiimide as activator. The reaction product obtained has a protein content of 35–110 mg/g of polymer and a proteolytic activity between 20.85–28.75 μmol tyrosine/L·min·g of polymer). The coupling reaction rate is maximum under the following conditions: pepsin/BIOZAN R ratio = 0.52 g/g, DCCI/BIOZAN R ratio = 0.2 g/g, pH = 3.4, reaction time = 4 h.     

Electroinitiated Polymerization of 3,3-BIS(N-Carbazolylmethyl)Oxetane

Abstract

3,3-Bis(N-carbazolylmethyl)oxetane, a cyclic compound with carbazolyl substituents closely linked to the oxetane ring, was polymerized by electrochemical initiation in aprotic polar solvents using a quaternary ammonium salt as electrolyte. Colored polymers were obtained as thin films deposited on the anode and were characterized by IR, ¹H NMR, and thermogravimetry. The data obtained refute the classical cationic polymerization of oxetanes.     

Unusual Structure,Fluxionality, and Reaction Mechanism of Carbonyl Hydrosilylation by Silyl Hydride Complex [(ArN)Mo(H)(SiH2Ph)(PMe3)3]

The reactions of bis(borohydride) complexes [(RN?)Mo(BH₄)₂(PMe₃)₂] ( 4 : R=2,6‐Me₂C₆H₃; 5 : R=2,6‐iPr₂C₆H₃) with hydrosilanes afford new silyl hydride derivatives [(RN?)Mo(H)(SiR′₃)(PMe₃)₃] ( 3 : R=Ar, R′₃=H₂Ph; 8 : R=Ar′, R′₃=H₂Ph; 9 : R=Ar, R′₃=(OEt)₃; 10 : R=Ar, R′₃=HMePh). These compounds can also be conveniently prepared by reacting [(RN?)Mo(H)(Cl)(PMe₃)₃] with one equivalent of LiBH₄ in the presence of a silane. Complex 3 undergoes intramolecular and intermolecular phosphine exchange, as well as exchange between the silyl ligand and the free silane. Kinetic and DFT studies show that the intermolecular phosphine exchange occurs through the predissociation of a PMe₃ group, which, surprisingly, is facilitated by the silane. The intramolecular exchange proceeds through a new non‐Bailar‐twist pathway. The silyl/silane exchange proceeds through an unusual Mo^VI intermediate, [(ArN?)Mo(H)₂(SiH₂Ph)₂(PMe₃)₂] ( 19 ). Complex 3 was found to be the catalyst of a variety of hydrosilylation reactions of carbonyl compounds (aldehydes and ketones) and nitriles, as well as of silane alcoholysis. Stoichiometric mechanistic studies of the hydrosilylation of acetone, supported by DFT calculations, suggest the operation of an unexpected mechanism, in that the silyl ligand of compound 3 plays an unusual role as a spectator ligand. The addition of acetone to compound 3 leads to the formation of [trans‐(ArN)Mo(OiPr)(SiH₂Ph)(PMe₃)₂] ( 18 ). This latter species does not undergo the elimination of a Si? O group (which corresponds to the conventional Ojima′s mechanism of hydrosilylation). Rather, complex 18 undergoes unusual reversible β‐CH activation of the isopropoxy ligand. In the hydrosilylation of benzaldehyde, the reaction proceeds through the formation of a new intermediate bis(benzaldehyde) adduct, [(ArN?)Mo(η²‐PhC(O)H)₂(PMe₃)], which reacts further with hydrosilane through a η¹‐silane complex, as studied by DFT calculations.     

Multivalent Recognition of Concanavalin A by {Mo132} Glyconanocapsules—Toward Biomimetic Hybrid Multilayers

Herein, we consider Müller’s spherical, porous, anionic, molybdenum oxide based capsule, (NH₄)₄₂‐ [{(Mo^VI)Mo^VI₅O₂₁(H₂O)₆}₁₂{Mo^V₂O₄(CH₃COO)}₃₀]?10 CH₃COONH₄? 300 H₂O≡(NH₄)₄₂? 1 a ?crystal ingredients≡ 1 , {Mo₁₃₂}, as an effective sugar‐decorated nanoplatform for multivalent lectin recognition. The ion‐exchange of NH₄⁺ ions of 1 with cationic‐sugars, D ‐mannose‐ammonium chloride ( 2 ) or D ‐glucose‐ammonium chloride ( 3 ) results in the formation of glyconanocapsules (NH₄)_42?n 2 _n? 1 a and (NH₄)_42?m 3 _m? 1 a . The Mannose (NH₄)_42?n 2 _n? 1 a capsules bind selectively Concanavalin A (Con A) in aqueous solution, giving an association avidity constant of ${K{{{\rm multi}\hfill \atop {\rm a}\hfill}}}$ =4.6×10⁴ M ^?1 and an enhancement factor of β=K${{{{\rm multi}\hfill \atop {\rm a}\hfill}}}$ /K${{{{\rm mono}\hfill \atop {\rm ass}\hfill}}}$ =21.9, reminiscent of the formation of “glycoside clusters” on the external surface of glyconanocapsule. The glyconanocapsules (NH₄)_42?n 2 _n? 1 a and (NH₄)_42?m 3 _m? 1 a self‐assemble in “hybrid multilayers” by successive layer‐by‐layer deposition of (NH₄)_42?n 2 _n? 1 a or (NH₄)_42?m 3 _m? 1 a and Con A. These architectures, reminiscent of versatile mimics of artificial tissues, can be easily prepared and quantified by using quartz crystal microgravimetry (QCM). The “biomimetic hybrid multilayers” described here are stable under a continual water flow and they may serve as artificial networks for a greater depth of understanding of various biological mechanisms, which can directly benefit the fields of chemical separations, sensors or storage‐delivery devices.     

Polymerization in a magnetic field. X. Solvent effect in poly(methyl methacrylate) synthesis

The effect of a continuous external magnetic field on the free radical polymerization of methyl methacrylate was studied with respect to some properties of the solvents used in the reaction. The studies were performed through dilatometric technique in and out a magnetic field of 0.25 T. Ten different solvents were used to underline the dependence between the magnetic field presence, the reaction medium, and the development of the polymerization process. The intervened magnetokinetic effects are attributed to the changes in the multiplicity of the radical pairs owing to the magnetic field influence. There is an interdependence among the viscosity and molar polarization of the solvents and the magnetic field effect. © 1996 John Wiley & Sons, Inc.