Transition metal chemistry - a review:

Transition metals are atoms that are filling their d orbitals.

Fe (II) has 6 valence electrons (it is filling the 3d orbitals)
Fe (III) has 5 valence electrons (it is filling the 3d orbitals)

Fe^o = 1s² 2s² 2p⁶ 3s² 3p⁶ 4s² 3d

Upon ionization, iron loses the 4s2 electrons, leaving its 6 d electrons

Co-ordination chemistry:

Co-ordination compounds are formed when transition metal ions interact with other ions or molecules, called ligands, possessing unshared pairs of electrons. The bonding that occurs between full positive charge(s) on the metal ion and the unshared electrons of the ligand (a partial negative charge) is electrostatic in nature. The electrical field produced by the ligands is called the ligand field, and is described by crystal field theory (sometimes called ligand field theory).

Two forces come into balance during the formation of co-ordination complexes:

1. ligands (in the case of heme, N:) are attracted to metal M+ (electrons of the ligand and the positive charge of metal ion).

2. the ligand - metal ion repulsion; electrons of the metal ion collide with the d-electrons of the ligands.

As the ligand (N:) approaches M+ there is a repulsive interaction between the outermost (d-orbitals) electrons of the metal and the ligand's electrons.

Heme proteins exist as ocathedral (eight sides) complexes; the heme provides four ligands and the protein + water provide the remaining two.

Hund's rule for filling orbitals with electrons states that electrons will be added to orbitals in a fashion such as to maximize the number of parallel spins. This is a reflection of the observation that spin paired (one spin up and one down) electrons represent a higher energy level and are not favored.

Electrons pair only when all d orbitals are full, or the energy differences between the d orbitals increases significantly.

Myoglobin structure:

Myoglobin (Mb) lacks symmetry, it is extremely compact (4.5 x 3.5 x 2.5 nm) versus its extended amino acid sequence.

75% of the amino acids are folded as -helix; they occur in 8 major helical segments.

Interior residues contain mainly hydrophobic side chains (in fact the X-ray structure of Mb provided data for formulation of hydrophobic model of protein folding).

Heme lies in a crevice in myoglobin molecule; the propionate side chains of heme, which are charged at physiological pH's, are at surface of molecule (most stable configuration!).

Fe is 0.03 nm out in the plane of the heme ring, due to the nature of the occupancy of d orbitals in the iron. As we will see later, the occupancy of these orbitals will change as oxygen approaches the iron ion during binding.

Two functions of the protein portion of heme proteins

Heme containing iron in its ferrous oxidation state is capable of binding oxygen, so why is it also necessary to have a protein (globin)?

In aqueous solution two heme irons can ligand a single molecule of oxygen:

                                     
      Heme --->       N-------Fe2+--------N
                                         O2                  
      Heme --->       N-------Fe2+--------N
                                                                                                                  O2   +  2 Fe2+  + 2 H+  --->  2 Fe3+  +  H2O2  

When two free hemes complex oxygen, the heme irons are oxidized from ferrous to ferric and hydrogen peroxide is generated. This reaction destroys oxygen binding capacity of the hemes; it is known that this reaction requires the "sandwiching" of two hemes.

The protein portion of heme proteins serves two functions:

1. it prevents the oxidation of Fe²⁺, preventing the loss of oxygen binding

2. it prevents the attendant formation of peroxides, which are destructive to other molecules in the cell (including DNA).