Synthetic models for hemoglobin and myoglobin

James P. Collman*, Lei Fu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

197 Citations (Scopus)

Abstract

Since the invention of the picket fence porphyrin, many attempts have been made to elucidate the factors responsible for gas binding specificity in hemoproteins. This account summarizes our contributions with model compounds. Emphasis is placed on our recent success in the design and synthesis of functional heme models. In this work, we present a class of aza-capped porphyrins that demonstrate the profound effects steric interactions can have on porphyrin CO affinity. With a series of iron and cobalt picnic basket porphyrins we have examined the dipole-dipole or H-bonding interaction between the terminally bound dioxygen and the amide protons. Comparison of their O2 affinities indicates that electrostatic interactions between the amide groups of the picnic basket porphyrin and the CoO2 species are more sensitive to the change of basket sizes than those of the corresponding FeO2 species; this is consistent with proposals that the CoO2 adducts have more electron density in the O2 ligand than do the FeO2 adducts. We have also studied dendritic Fe(II) porphyrins as T-state Hb models. These dendritic porphyrins exhibit CO affinities similar to those of Hb but remarkably higher O2 affinities, approaching that of Hb Ascaris. This striking result indicates that (1) as with Hb, bound CO experiences a destabilizing influence and (2) a H-bond between the terminal atom of bound O2 and an amide group can drastically increases O2 affinity. Our studies on heme models provide fundamental insights into the nature of O2 adduct stabilization and CO ligand destabilization in hemoproteins. Many issues remain unanswered, however. For instance, is the binding affinity affected predominantly by a single factor or by multiple factors? Does a steric effect that sharply reduces CO affinity actually require an observable geometric distortion? What are the spectroscopic signatures of this distortion? What is the role of kinetics versus thermodynamics? Resolution of these issues may provide further insights into ligand binding and discrimination in native hemoglobin and myoglobin.

Original languageEnglish
Pages (from-to)455-463
Number of pages9
JournalAccounts of Chemical Research
Volume32
Issue number6
DOIs
Publication statusPublished - 1999
Externally publishedYes

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