Marco A. Lopez

University of California, San Diego, San Diego, California, United States

Are you Marco A. Lopez?

Claim your profile

Publications (5)31.62 Total impact

  • Marco A. Lopez · Cynthia D. Ybarra · Stephanie Hyatt
    [Show abstract] [Hide abstract]
    ABSTRACT: Photolysis of CO and 1-methylimidazole (1-MeIm) mixtures of protoheme monomethyl ester, mono[3-(1-imidazoyl)propyl]amide (monochelated protoheme, or mcph) in toluene is followed over a time period of minutes. Reactions are followed under pseudo-first-order conditions, and the difference spectra recorded for each kinetic run show multiple isosbestic points. Intercepts from plots of the reciprocals of the observed rate constants versus 1-methylimidazole concentration suggest the initial mcph-CO complex has the internal base displaced by external 1-methylimidazole. Photolysis of this mcph(1-MeIm)(CO) complex yields mcph(1-MeIm) (5) which is five-coordinated, with the internal imidazole not attached to the iron atom. Prior to CO recombination, 5 forms a rapid equilibrium with the two hexacoordinated forms, mcph(1-MeIm)2 (6) and mcph(1-MeIm) (3), which decays to form the CO complex mcph(1-MeIm)(CO) (species 6, like species 5,has the internal base unbound to the iron atom whereas species 3 has the internal imidazole bound to the iron atom). Based on values relative to the rate of CO association to 5, estimates are made for the binding constant of a second mole of 1-MeIm to form 6, (6±2) × 105 M−1, and the chelation constant of the internal imidazole to form 3, (8±3) ×103. Comparison with similar compounds taken from the literature reveal that, in addition to the dependence on the length of the side-arm (F.A. Walker and M. Benson, J. Am. Chem. Soc., 102 (1980) 5530–5538), chelation is dependent on solvent, structure of the base, structure of the porphyrin, and whether the iron is four- or five-coordinated — the binding of side-arm bases is poorer to a five-coordinated heme than to a four-coordinated heme, contrary to traditional behavior.
    Inorganica Chimica Acta 03/1995; 231(1):121-131. DOI:10.1016/0020-1693(94)04327-R · 2.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Detailed solution kinetic and equilibria data (mainly in toluene) are presented for the reversible binding of CO and O2 to the five-coordinate hemes Fe(por)B, where B is 1,5-dicyclohexylimidazole or 1,2-dimethylimidazole (chosen to mimic the R- and T-states, respectively) and por = the dianion of some durene-capped porphyrins with variable length linking methylene straps on either side of the durene moiety (4/4, 5/5, or 7/7 methylenes). Use of spectrophotometric equilibrium titrations from 30 to -50-degrees-C, stopped-flow data, and laser flash photolysis under either CO or CO/O2 mixtures, has allowed for determination of on and off rates, equilibrium constants, and, in the case of the 4/4-system, thermodynamic constants for the binding. Increasing steric hindrance provided by the durene cap, in the order 7/7 < 5/5 < 4/4, is generally less than expected from studies with other heme derivatives; in combination with the complete absence of polarity effects, as within nonpolar distal sites, the durene hemes exhibit poor differentiation between CO and O2. However, the distorted 4/4-derivative discriminates between CO and O2 in a novel way through a ''proximal effect'' associated with deformation of the porphyrin skeleton from planarity, the effect being largely reflected by an increased CO dissociation rate.
    Journal of the American Chemical Society 01/1994; 116(1). DOI:10.1021/ja00080a002 · 12.11 Impact Factor
  • Source
    Marco A. Lopez · Peter A. Kollman
    [Show abstract] [Hide abstract]
    ABSTRACT: The protein contribution to the relative binding affinity of the ligands CO and O2 toward myoglobin (Mb) has been simulated using free energy perturbation calculations. The tautomers of the His E7 residue are different for the oxymyoglobin (MbO2) and carboxymyoglobin (MbCO) systems. This was modeled by performing two-step calculations that mutate the ligand and mutate the His E7 tautomers in separate steps. Differences in hydrogen bonding to the O2 and CO ligands were incorporated into the model. The O2 complex was calculated to be 2-3 kcal/mol more stable than the corresponding CO complex when compared to the same difference in an isolated heme control. This value agrees well with the experimental value of 2.0 kcal/mol. In qualitative agreement with experiments, the Fe-C-O bond is found to be bent (theta = 159.8 degrees) with a small tilt (theta = 6.2 degrees). The contributions made by each of the 29 residues--within the 9.0-A radius of the iron atom--to the free energy difference are separated into van der Waals and electrostatic contributions; the latter contributions are dominant. Aside from the proximal histidine and the heme group, the residues having the largest difference in free energy in mutating MbO2-->MbCO are His E7, Phe CD1, Phe CD4, Val E11, and Thr E10.
    Protein Science 11/1993; 2(11):1975-86. DOI:10.1002/pro.5560021119 · 2.85 Impact Factor
  • Marco A. Lopez · Peter A. Kollman
    [Show abstract] [Hide abstract]
    ABSTRACT: The authors present the application of molecular mechanics/dynamics and free energy perturbation computational techniques to simulation of iron(II) porphyrin systems. Force field parameters were developed by modeling the geometry of four systems whose crystal structure is known. This force field was then used in molecular dynamics/free energy perturbation calculations at 300 K in vacuo, on a separate set of four iron(II) porphyrin systems including models of 5,5-pyridine cyclophane heme (1,5-DCI) (I), picket fence heme(2-MeIm) (II), monochelated heme (III), and 7,7-durene cyclophane heme(1,5-DCI) (IV). The perturbation calculations reproduced reasonably well the trend in the partition coefficient, M value, of this set. Their simplified model indicates that the electrostatic component of both I and II factors the binding of Oâ over CO, whereas the electrostatic component of III and IV favors CO over Oâ. The preference of Oâ over CO binding from the nonbonded steric component was I > II > III > IV. Molecular dynamics simulations showed that the Fe atom of the Oâ and CO complexes of I oscillated 0.06 and 0.16 â«, respectively, lower than those of II, even though the crystal structure and the simulation of the Oâ complex of II shows the Fe atom 0.087 â« below the porphyrin plane: this result suggests that the ratios of R state to T state CO/Oâ binding affinities will be extremely low for system 1. The simulations also showed that even with a 7,7-strap as in IV, there is still more interaction with a bound CO than with a bound Oâ.
    Journal of the American Chemical Society 08/1989; 111(16):6212-6222. DOI:10.1021/ja00198a036 · 12.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We present the results of simulations on spherands, crown ethers and hemes, using com- puter graphics, distance geometry, molecular mechanics and molecular dynamics. In the spherand calculations, we show how a combined use of distance geometry, computer graphics and molecular mechanics led to the prediction of a new spherand isomer with high Li' and Na' affinity. In the area of crowns, we simulated the relative cation affinities of dibenzo 18srown-6 and dibenzo 30crown- 10, using molecular dynamics and free energy perturbation theory and found good agreement with the relative experimental free energies of ion binding. For the hemes, we simulated the relative free energy of association of CO and O2 in different porphyrim using molecular dynamics and free energy perturbation approaches and found a reasonable agreement between the calculated and exper- imental relative CO/02 affinity.
    Pure and Applied Chemistry 01/1989; 61(3):593-596. DOI:10.1351/pac198961030593 · 2.49 Impact Factor

Publication Stats

95 Citations
31.62 Total Impact Points


  • 1994
    • University of California, San Diego
      • Department of Chemistry and Biochemistry
      San Diego, California, United States
  • 1993
    • California State University, Long Beach
      • Department of Chemistry & Biochemistry
      Long Beach, CA, United States
  • 1989
    • University of California, San Francisco
      • Department of Pharmaceutical Chemistry
      San Francisco, California, United States