Computer-aided simulation of a dendrimer with a protoporphyrinic core as potential, novel hemoprotein mimic.

In this work, we have inserted the ion-heme group characterizing human blood in a class of synthetic, dendrimeric macromolecules, to evaluate a series of structural and physico-chemical properties related to the possible biological activity of these polymers. To this purpose, we have performed a complete series of investigations of five dendrimer generations both in vacuum and in water by molecular mechanics/dynamics simulations. To mimic oxygen binding, we have studied the same molecules in which the protoporphyrinic core was complexed to a Fe(II)-O(2)-hystidine residue. The main results of this study have led us to conclude that all dendrimer generations can bind oxygen stably, the fifth generation being the most affine to the myoglobin molecule, the natural carrier of blood oxygen.

[1]  L. Verlet.  Computer "Experiments" on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules , 1967 .

[2]  W. Goddard,et al.  Charge equilibration for molecular dynamics simulations , 1991 .

[3]  W. Robinson,et al.  "Picket fence porphyrins." Synthetic models for oxygen binding hemoproteins. , 1975, Journal of the American Chemical Society.

[4]  K. Birdi.  Fractals in Chemistry, Geochemistry, and Biophysics , 1993, Springer US.

[5]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[6]  T. Aida,et al.  A dendritic iron porphyrin as a novel haemoprotein mimic: effects of the dendrimer cage on dioxygen-binding activity , 1996 .

[7]  R. Poljak,et al.  Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution , 1986, Science.

[8]  Christopher A. Reed,et al.  Synthetic Heme Dioxygen Complexes , 1994 .

[9]  William A. Goddard,et al.  Starburst Dendrimers: Molecular‐Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter , 1990 .

[10]  諏訪 紀夫,et al.  Morphological and morphormetrical analysis of circulation in hypertension and ischemic kidney , 1971 .

[11]  K. Arai,et al.  Synthesis and dioxygen-binding properties of double-sided porphyrinatoiron(II) complexes bearing covalently bound axial imidazole , 1993 .

[12]  William A. Goddard,et al.  Starburst dendrimers. 5. Molecular shape control , 1989 .

[13]  Benno P. Schoenborn,et al.  Neutron diffraction reveals oxygen–histidine hydrogen bond in oxymyoglobin , 1981, Nature.

[14]  M. Fermeglia,et al.  Molecular simulation of host–guest inclusion compounds: an approach to the lactodendrimers case , 2001 .

[15]  M. L. Connolly.  Analytical molecular surface calculation , 1983 .

[16]  J. Almog,et al.  Reversible oxygenation and autoxidation of a capped porphyrin iron(II) complex , 1975 .

[17]  Arnold T. Hagler,et al.  New combining rules for rare gas van der waals parameters , 1993, J. Comput. Chem..

[18]  B. Ward,et al.  Nonbonding steric effect on carbon monoxide and oxygen binding to hemes. Kinetics of ligand binding in iron-copper cofacial diporphyrins and strapped hemes , 1981 .

[19]  S. Frauendorf,et al.  The influence of 1QP-state equilibrium deformations on E1 transition probabilities , 1973 .

[20]  H. C. Andersen.  Molecular dynamics simulations at constant pressure and/or temperature , 1980 .

[21]  Michael L. Connolly,et al.  Computation of molecular volume , 1985 .

[22]  M. Fermeglia,et al.  Dendrimers as Functional Materials. A Molecular Simulation Study of Poly(propylene) Imine Starburst Molecules , 2000 .

[23]  P. Gennes,et al.  Statistics of « starburst » polymers , 1983 .

[24]  Maurizio Fermeglia,et al.  Equation‐of‐state parameters for pure polymers by molecular dynamics simulations , 1999 .

[25]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[26]  Benoit B. Mandelbrot,et al.  Fractal Geometry of Nature , 1984 .

[27]  M. Lewis,et al.  Fractal surfaces of proteins. , 1985, Science.

[28]  Donald J. Cram.  The Design of Molecular Hosts, Guests, and Their Complexes (Nobel Lecture)† , 1988 .

[29]  F. Vögtle,et al.  Dendritic Molecules: Concepts, Syntheses, Perspectives , 1996 .

[30]  W. Goddard,et al.  UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations , 1992 .

[31]  J. I. Brauman,et al.  Synthesis and characterization of the "pocket" porphyrins , 1983 .

[32]  C. Hawker,et al.  Synthesis and Properties of Dendrimers and Hyperbranched Polymers , 1996 .