Electrostatic interactions effect in the aminolysis of some β‐lactams in the presence of poly(ethyleneimine):structure‐reactivity

The aminolysis reaction of a series of β-lactams in the presence of poly(ethyleneimine) (PEI) at 30°C and pH = 8.40 has been studied. The substrates investigated follow a pseudo first order rate, except two β-lactams which show a two step consecutive reaction. Increasing the polyelectrolyte concentration, Michaelis–Menten type kinetics are been observed and for four substrates a more complex rate behaviour was verified owing to the polyelectrolyte inhibition effect. Both the binding constant K1 between polyelelectrolyte and β-lactam and the first order rate constant of the reactive complex decomposition kcat were calculated. The substituent effect at C-6′ or C-7′ position of β-lactam on the aminolysis rate does not correlate with the σI value (Taft plot). Most probably, steric and electronic effects are important, but the electrostatic ones are determining factors for the relevant acceleration attributable to both the binding phenomena and the increased reactivity of the substrate–polyelectrolyte complex. The comparison between poly(ethyleneimine) and Human Serum Albumin (HSA) is also discussed. Copyright © 2007 John Wiley & Sons, Ltd.

[1]  D. Gazzard,et al.  Penicillin Allergy: The Formation of the Penicilloyl Determinant , 1965, Nature.

[2]  B. Nerli,et al.  Structural specificity requirements in the binding of beta lactam antibiotics to human serum albumin. , 1997, Chemico-biological interactions.

[3]  P. Taboada,et al.  Protein-ligand interactions: Volumetric and compressibility characterization of the binding of two anionic penicillins to human serum albumin , 2003 .

[4]  T. Okubo,et al.  Polyelectrolyte "Catalysis" on the Interionic Reactions between Similarly Charged Polyvalent Ions± , 1980 .

[5]  G. Phillips,et al.  Ion binding of penicillins to proteins. , 1970, Biochimica et biophysica acta.

[6]  J. Suh,et al.  Activation and stabilization of chymotrypsin in microdomains of poly(ethylenimine) derivatives. A model of in vivo environment. , 1998, Bioorganic & medicinal chemistry letters.

[7]  D. Scherman,et al.  A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. Tsuji,et al.  Chemical reactions involved in penicillin allergy: kinetics and mechanism of penicillin aminolysis , 1975, The Journal of pharmacy and pharmacology.

[9]  M. Page,et al.  Mechanism of .beta.-lactam ring opening in cephalosporins , 1984 .

[10]  M. Page.  The Chemistry of enzyme action , 1984 .

[11]  S. Creighton,et al.  Enzymes work by solvation substitution rather than by desolvation. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Arcelli,et al.  Mechanistic investigation of an anomalous anchimeric assistance in the acid hydrolysis of the ether linkage. Part 4 , 2001 .

[13]  C. Schneider,et al.  A New Chemical Aspect of Penicillin Allergy: The Direct Reaction of Penicillin with ɛ-Amino-Groups , 1965, Nature.

[14]  T. Okubo,et al.  Synthetic polyelectrolytes as models of nucleic acids and esterases , 1977 .

[15]  P. J. Taylor.  On the calculation of tetrahedral intermediate pKa values , 1993 .

[16]  H. Morawetz,et al.  Catalysis of ionic reactions by polyelectrolytes. II. Electron transfer between cobalt(III) complexes and iron(II) in solutions of poly(vinylsulfonate) , 1970 .

[17]  W. H. Hall,et al.  Determination of binding constants of serum albumin for penicillin. , 1969, The Journal of pharmacology and experimental therapeutics.

[18]  S. N. Rao,et al.  Structure-reactivity relationship for base-promoted hydrolysis and methanolysis of monocyclic .beta.-lactams , 1990 .

[19]  T. Maruno,et al.  Role of solvation and desolvation in polymer ‘catalysis’. I. The influence of high pressures on the spontaneous and Ag+-induced aquations of Co(NH3)5Br2+ catalysed by macro-ions , 1980, Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences.

[20]  D. D. Perrin,et al.  pKa prediction for organic acids and bases , 1981 .

[21]  D. Carter,et al.  Atomic structure and chemistry of human serum albumin , 1992, Nature.

[22]  Y. Matsumoto,et al.  Structure-binding relationship and binding sites of cephalosporins in human serum albumin. , 1992, The Journal of antibiotics.

[23]  A. Arcelli,et al.  Benzylpenicillin cleavage with polyelectrolytes , 2005 .

[24]  J. Wal,et al.  Identification of the binding sites of benzyl penicilloyl, the allergenic metabolite of penicillin, on the serum albumin molecule , 1990, FEBS letters.

[25]  J. Wal,et al.  Binding of benzyl penicilloyl to human serum albumin Evidence for a highly reactive region at the junction of domains 1 and 2 of the albumin molecule , 1989, FEBS letters.

[26]  N. Gensmantel,et al.  The chemical reactivity of penicillins and other β-lactam antibiotics , 1982 .

[27]  K. Kobayashi,et al.  Crystal structure of human serum albumin at 2.5 A resolution. , 1999, Protein engineering.

[28]  A. J. Kirby,et al.  Effective Molarities for Intramolecular Reactions , 1980 .

[29]  H. D. Rapson,et al.  IONISATION CONSTANTS OF SOME PENICILLINS AND OF THEIR ALKALINE AND PENICILLINASE HYDROLYSIS PRODUCTS , 1963, The Journal of pharmacy and pharmacology.

[30]  P. Demoly,et al.  Update on beta-lactam allergy diagnosis , 2005, Current allergy and asthma reports.

[31]  I. A. Volkova,et al.  Acid-Base Properties of Some Penicillins , 2003 .

[32]  N. Gensmantel,et al.  Metal-ion catalysed hydrolysis of some β-lactam antibiotics , 1980 .

[33]  K. Terao,et al.  4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride: an efficient condensing agent leading to the formation of amides and esters , 1999 .

[34]  R. Pratt,et al.  Elimination of a good leaving group from the 3'-position of a cephalosporin need not be concerted with .beta.-lactam ring opening: TEM-2 .beta.-lactamase-catalyzed hydrolysis of pyridine-2-azo-4'-(N',N'-dimethylaniline) cephalosporin (PADAC) and of cephaloridine , 1984 .

[35]  M. Charton,et al.  Definition of “Inductive” Substituent Constants , 1964 .

[36]  T. Terasaki,et al.  Relationship between lipophilicity and binding affinity with human serum albumin for penicillin and cephem antibiotics. , 1992, Journal of pharmacobio-dynamics.

[37]  Lemont B. Kier,et al.  QSAR modeling of β-lactam binding to human serum proteins , 2003, J. Comput. Aided Mol. Des..

[38]  A. Arcelli.  Polyelectrolyte-catalyzed acetyl transfer reactions. Aminolysis of phenyl acetates by poly(ethylenimine) : Catalytic, inhibition, and solvent effects and thermodynamic parameters , 1999 .