Albert Zilkha

Attachment of drugs to polyethylene glycols

Abstract Polyethylene glycol (PEG) was used as a carrier polymer for the attachment, via end groups, of drugs such as penicillin V, aspirin, amphetamine, quinidine and atropine. For this purpose, methods were developed for the functionalization of PEG; PEG-NH 2 , PEG-COOH and PEG-NCO were prepared. Use was made of dicyclohexyl carbodiimide together with 4-dimethylamino pyridine or 1-hydroxybenzotriazole for the coupling reactions.

Monomers for non-bond crosslinking of vinyl polymers

Abstract Monomers having on the one hand a polymerizable double bond and on the other hand a large macrocyclic ring (n≥27–28) through which a growing chain may be threaded are shown to be a new type of crosslinking agents which lead to non-bond crosslinking of vinyl polymers. This is demonstrated by cyclic octaethylene glycol fumarate, a 29-membered ring obtained in the reaction of fumaryl chloride with octaethylene glycol under high dilution conditions, which upon copolymerization with styrene or methylmethacrylate led to crosslinked polymers.

Esterification of Polyethylene Glycols

Abstract Esterification of polyethylene glycols by various carboxylic acids in high yield and high substitution levels is described. The esterification reaction is achieved by dicyclohexylcarbodiimide and catalyzed by dimethylaminopyridine. Rate measurements indicated that the reaction is complete after 2 h at room temperature.

Use of the “interfacial polymerization method” for the preparation of organotin esters

Abstract The “interfacial polymerization” method was utilized for the preparation of organotin esters. Trialkyl- or triaryl-tin chlorides, dialkyltin dichlorides and tetraalkydichlorodistannoxanes, dissolved in an inert solvent, were reacted with an aqueous solution of an alkali metal salt of a mono- or dicar☐ylic acid, to yield the organotin esters in high yield.

Monomers for non-bond crosslinking of vinyl polymers: II. Cyclic octaethylene glycol 5-methacrylamido-isophthalate

The new concept of non-bond crosslinking of vinyl polymers is demonstrated with cyclic octaethylene glycol 5-methacrylamido-isophthalate, which was synthesized and copolymerized with methyl methacrylate to yield insoluble copolymers with a high swelling capacity, threading of polymer chains through the rings being the cause of the crosslinking. Evidence for the threading was obtained from 2D nuclear magnetic resonance.

Attachment of drugs to polydimethylsiloxanes

Abstract Polydimethylsiloxane, which is a biologically inert polymer, was used as a carrier polymer for drugs. Functional groups were introduced into the polymer to enable attachment to drugs. Polymers (and oligomers) having carboxyl, amine or hydroxyl groups were prepared from polydimethylsiloxanes having different distributions of SiH groups which were added to the C=C double bond of unsaturated acids, amines or alcohols. These polymers were reacted with suitable functional groups on drugs such as digoxin, quinidine, barbiturates, amphetamine, naloxone and atropine.

Oligotrimerization of hexamethylene diisocyanate by organometallic catalysts

The oligotrimerization of hexamethylene diisocyanate by tributylin oxide (TBTO), Zr(OBu)4, Ti(OBu)4 and Pb-naphthenate was studied. For mild reaction conditions, i.e. weak catalyst (TBTO), low catalyst concentration and temperature, the reaction gave selectively the cyclic trimer (I) and not higher oligomers.

Observations on the Anionic Polymerization of Ethylene Oxide by Alkali Metal Naphthalene and Anthracene Complexes

Abstract The anionic polymerization of ethylene oxide by alkali metal naphthalenes and anthracenes was studied in DMSO and THF to determine the effects of solvent and of polycyclic hydrocarbon, and to obtain information on the mode of initiation. No propagation occurred with lithium naphthalene, and this made it possible to isolate mono- and dihydroxyethyl naphthalene, the species formed on initiation. The molecular weights obtained in the presence of DMSO were about half those obtained in THF, and were proportional to [monomer]/[initiator]. This was explained as being due to differences in initiation; i.e., formation of dimsyl anion as the true initiator in DMSO. The rate of polymerization was first order to monomer, and the molecular weights were found to increase linearly with percent inversion.

Grafting of single amino-acid units to polyhydroxy polymers

Abstract The reaction between N-carboxy anhydrides (NCAs) of amino acids and polymeric alkoxide derivatives of polyhydroxypolymers such as cellulose acetate in solution at (A/I) ratios of NCA to alkoxide⩽1 was investigated. Amino-acid derivatives of the polyhydroxypolymers were thus obtained in which essentially single amino-acid units were attached to the polymeric backbone through either their carboxyl or amino group, as seen from end group titrations. NCAs of α-amino acids and N-substituted α- and β-amino acids were used. The reaction at A/I ratios between 1 and 4, led to the attachment of polypeptide side chains whose DP n was given by A/I. The percentage terminal amino groups increased on increasing the A/I ratio above unity. The results obtained may help to elucidate the initiation mechanism of the polymerization of NCAs by alkoxides; this has been a subject of controversy.

Monomers for non-bond crosslinking of vinyl polymers. III. Some characteristics of the system

Abstract In the new type of non-bond crosslinking where a vinyl macrocycle acts as the crosslinking agent, it is shown that factors affecting threading of polymer chains into macrocyclic rings which lead to crosslinking, such as ring size, ratio of co-monomer to cyclic monomer and length of the vinyl polymer chain are important factors that govern the extent of the crosslinking. They also affect the swelling of the crosslinked copolymers in various solvents, as well as their thermal properties. Some differences from conventional crosslinking using difunctional vinyl monomers are pointed out.