Murat Acemoglu

Poly(ethylene carbonate)s, part I : Syntheses and structural effects on biodegradation

Poly(ethylene carbonate)s (PECs) of different molecular weights (Mws) were synthesized by copolymerization of CO2 and ethylene oxide using different catalyst systems. Et2Zn/ethylene glycol was found to be exceptionally effective as a catalyst for this copolymerization. PECs synthesized using this catalyst were characterized by very high ethylene carbonate content, low polydispersity and high glass transition temperatures. The in vivo biodegradability of PECs was found to be affected by the content of ether functions in the polymer chain, by the Mw of the products and by the catalyst used to prepare them. Surprisingly, the biodegradation of PECs having Mws 130 000 show almost identical in vivo biodegradation by surface erosion.

Poly(ethylene carbonate)s, part II: degradation mechanisms and parenteral delivery of bioactive agents.

The degradation and drug carrier properties of poly(ethylene carbonate) (PEC) were investigated in vitro and in rats and rabbits. PEC was found to be specifically degraded in vivo and in vitro by superoxide radical anions O2-*, which are, in vivo, mostly produced by inflammatory cells. No degradation of PEC was observed in the presence of hydrolases, serum or blood. PEC is biodegraded by surface erosion without significant change in the molecular weight of the residual polymer mass. The non-hydrolytic biodegradation by cells producing O2-* is unique among the polymers used as biodegradable drug carriers. The main degradation product of PEC in aqueous systems is ethylene glycol, formed presumably by hydrolysis of ethylene carbonate. The splitting off of a five-membered ring structure from the polymer chain indicates a chain reaction mechanism for the biodegradation. PEC is a suitable drug carrier, particularly for labile drugs. Using human interleukin-3 and octreotide as model drugs, surface erosion of the PEC formulations was indicated by a 1:1 correlation between drug release and polymer mass loss.

Synthesis of regioselectively substituted cellulose derivatives and applications in chiral chromatography

Various cellulose-2,3-bis-arylcarbamate-6-O-arylesters and cellulose-2,3-bis-arylester-6-O-arylcarbamates, designed to test the possible combined effects of the known tris-arylcarbamate and tris-arylester classes, were synthesized with high regioselectivity at O-C(6), and their use as CSPs in liquid chromatography for enantiomeric separations was investigated. The separations obtained with the synthesized CSPs were compared to the separations achieved on a self-packed reference column, consisting of cellulose-tris-(3,5-dimethylphenyl-carbamate) as CSP standard. Among the synthesized, regioselectively substituted cellulose derivatives, 2,3-bis-O-(3,5-dimethylphenylcarbamate)-6-O-benzoate-cellulose and 2,3-bis-O-(benzoate)-6-O-(3,5-dichlorophenylcarbamate)-cellulose gave the best CSPs for the separation of the test racemates. CSPs from regioselectively substituted cellulose derivatives seem to exhibit higher selectivities than cellulose-tris-(3,5-dimethylphenylcarbamate) for certain classes of racemic compounds. Chirality 10:294–306, 1998.

Tritium labelling of RAD001—a new rapamycin derivative

RAD0012, a new immunosuppressant, was labelled in its hydroxyethyl side chain as well as in the rapamycin skeleton using carrier-free lithium triethylborotritide and tributyltin tritide (TBTT), respectively. The tritium labelling of the rapamycin moiety followed Currans strategy of intramolecular hydrogen transfer. Our studies demonstrated that base-free TBTT is essential for a successful reaction. Copyright