1. Principles of Bioinorganic Chemistry - 2003 The grade for this course will be determined by a term exam (35%), a written research paper with oral presentation (45%), problem sets (12%) and classroom participation (8%). The oral presentations will be held in research conference style at MIT's Endicott House estate in Dedham, MA, on Saturday, October 18. Please reserve the date for there are no excused absences. Papers will be due approximately one week earlier. WEB SITE: web.mit.edu/5.062/www/

2. The Major Metal Units in ET Proteins (1) Iron-Sulfur Clusters

3. Properties of Iron-Sulfur Clusters (A) Rubredoxin Fe–S, 2.25 - 2.30 Å in oxidized (Fe III ) and reduced (Fe II ) states Reduction potentials: - 50 to + 50 mV (B) 2Fe-2S Ferredoxins (Fd) Fe II Fe II Fe III Fe III reducedmixed-valent oxidized all physiological uses Reduction potentials: -490 to - 280 mV (C) 3Fe-4S Ferredoxins (cube missing a corner) Fe III 3 S 4 Fe III 2 Fe II S 4 Reduction potentials: -700 to - 100 mV Reminder:  o = -RT/nF lnQ + pH, where Q = [M n ]/[M n-1 ] Thus, at pH 7, the biological H 2 /2H + standard couple is - 420 mV.

4. Properties of Iron-Sulfur Clusters, cont’d (D) 4Fe-4S Ferredoxins and High-potential Iron Proteins (HiPIPs) Fe II 3 Fe III Fe II 2 Fe III 2 Fe II Fe III 3 HiPIP Reduction potentials: -650 to - 280 mV (Fd); + 350 mV (HiPIP) The three state hypothesis: Ferredoxin minimal reorganizational energy

5. The Physical Properties of Iron-Sulfur Clusters

6. Primary structure (sequence) does not dictate the tertiary structure of a metalloprotein, as revealed by this 8-iron ferredoxin crystal structure. Structure of an 8Fe-8S Ferredoxin

7. The Major Metal Units in ET Proteins (2) Blue Copper and Cu A Depicted at the right are the three copper sites in the enzyme ascorbate oxidase. Type 1, or blue, copper is the ET center. Below is depicted Cu A. Blue Copper Cu A

8. The Physical Properties of Blue Copper Centers The deep sky blue color of these proteins facilitated their purification on columns; the optical band is Cu–S C.T.

9. Structure of Poplar Plastocyanin The oxidized, reduced and apo plastocyanin structures are nearly identical. The copper(II) thiolate center is difficult to model.

10. EPR Spectra Distinguish the Three Types of Copper Found in Metalloproteins

11. Cu A Model Chemistry: Reversible 1-Electron Transfer These complexes demonstrate that constrained dicopper(I/II) units afford good 1-electron reversible transfer centers and display the possible environments that could be encountered in biology. LeCloux Chuan He

12. The Major Metal Units in ET Proteins (3) Cytochrome c from tuna showing coordination of the iron porphyrin group by the protein side chains from Met (left) and His (right) residues.

13. Electronic Properties of Low-Spin Metalloporphyrins Note again, minimal reorganization energy upon electron transfer

14. Long-Distance Electron Transfer in Proteins Three ways to measure: 1. Self-exchange 2. Artificial donor-acceptor pairs 3. Study of natural protein redox pairs Red Az + Ox Az Ox Az + Red Az Cu I Cu II Cu II Cu I k = 1.3 x 10 6 M -1 s -1 for azurin

15. Artificial Donor-Acceptor Pairs Cytochrome c; Fe---Ru, ~12 Å