1. Ligands that Favor/Force the Formation of Tetrahedral Complexes with an Application in Bioinorganic Chemistry Marion E. Cass, Carleton College Michael J. Stevenson, Dartmouth College Molly L. Croteau, Dartmouth College Created by Michael J. Stevenson, Dartmouth College (Michael.J.Stevenson.GR@Dartmouth.edu) Molly L. Croteau, Dartmouth College (Molly.L.Croteau.GR@Dartmouth.edu) and Marion E. Cass, Carleton College (mcass@.carleton.edu), and posted on VIPEr on February 20, 2016. Copyright Michael J. Stevenson, Molly L. Croteau, and Marion E. Cass. This work is licensed under the Creative Commons Attribution Non-commercial Share Alike License. To view a copy of this license visit http://creativecommons.org/about/license/.Michael.J.Stevenson.GR@Dartmouth.eduMolly.L.Croteau.GR@Dartmouth.edumcass@.carleton.eduhttp://creativecommons.org/about/license/

2. M Ni II dmpI 2 Pt II dmpI 2 dmp = 2,9-dimethyl-1,10-phenanthroline Bidentate ligand w planar 1,10-phenanthroline methyl groups block the ability of a second dmp or other ligands to bind in the same plane Ni(II) d 8 forms a tetrahedral complex: Not Square Planar Pt(II) distorts to avoid tetrahedral coordination For 3D JSmol movable images see: http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/MdmpX2.html

3. Several other ligands that force tetrahedral geometry are known CCDC Reference: DICSIR J.S.L.Yeo, J.J.Vittal, T.S.A.Hor, Chem Commun. 1999, p. 1477 See: “A paramagnetic tetrahedral Pd(II) complex” Housecroft and Sharpe, Inorganic Chemistry 3 rd Ed, p. 671 Dichloro-(1,1'-bis(oxodiphenylphosphoranyl)ferrocenyl)-palladium(II) For a 3D JSmol movable image see: http://www.people.carleton.edu/~mcass/1-Inorganic- C351/jsmol/Pd-tdL-Cl2.html.html

4. A Bio-inorganic Application Dean Wilcox and his students at Dartmouth College carry out careful thermodynamics measurements to examine metal binding in metalloproteins Molly Croteau examines the binding of metal ions to Azurin (a blue copper electron transport protein). In azurin the copper metal ion shuttles between Cu(I) and Cu(II) in order to provide electrons to cytochrome c oxidase in bacterial cells. Binding of copper in both oxidation states to the apo-azurin is essential for understanding how this protein tunes its reduction potential to participate with cytochrome c oxidase in vivo. Michael Stevenson studies the binding of various metal ions to the copper metallochaperone protein HAH1. The reducing environment of the cell makes the predominant copper oxidation state to be Cu(I). HAH1 is finely tuned to bind Cu(I) and transport it through the cytosol for delivery to the trans Golgi network. Competition by other metal ions provides insight into ferreting out the structure/thermodynamic relationship that provides the selectivity for Cu(I). It also provides insight into potential mechanisms of heavy metal toxicity in this and other biochemical pathways. In both instances, it is crucial to know the oxidation state of the metal being delivered during a carefully controlled experiment. For Cu(I), this is not an easy experimental task.

5. Cu(I)L n + Apo-protein Cu(I)-protein Desired Experiment Measure Thermodynamics of Cu(I) binding to the protein in question + nL Experimental ChallengeSolution Cu(I) salts tend to be insoluble Find a ligand that will create a soluble Cu(I)L n complex Other species in solution (H 2 O, Buffer, Anions, etc) compete for the Cu(I) Find a ligand that will bind more strongly than H 2 O, Buffer, Anions etc ) Cu(I)L n complexes can disproportionate to form Cu(0) and Cu(II)L n species 2Cu I L n ⇌ Cu(0) + Cu II L n Find a ligand that forms a relatively stable Cu I L n complex to disfavor the disproportion reaction Cu(I) complexes can be oxidized in the presence of O 2 Cu I Ln + O 2  Cu II L n Again use a ligand that forms a relatively stable Cu I L n complex However most importantly, work in an O 2 free environment

6. Ligand 1: Me 6 Trien in O 2 Cu I Me 6 Trien will not disproportionate 2Cu I L Cu(0) + Cu II L And in fact: the reverse comproportion reaction is the preferred preparation method Cu II + Cu(0) + excess Me 6 Trien 2 Cu I L For 3D JSmol movable images see: http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/CuCuI-CuII-L.htm If O 2 free The Cu(I) will oxidize to Cu(II) and will pick up an additional L: anion or solvent Cu I L is the predominant Species in solution

7. Ligand 2: BCA in O 2 [Cu I BCA 2 ] 3- will not disproportionate 2[Cu I BCA 2 ] 3- Cu(0) + [Cu II BCA 2 ] 2- Cu I complex For 3D JSmol movable images see: http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/CuCuI-CuII-L.htm If O 2 free [Cu I BCA 2 ] 3- is the predominant species in soln The Cu II complex is believed to have a similar 3D structure to the Cu(I) complex. The crystal structure of the complex with one BCA analog and two Cl - Ligands is shown below Cu II complex

8. Ligand 3: BCS in O 2 [Cu I BCS 2 ] 3- will not disproportionate 2[Cu I BCS 2 ] 3- Cu(0) + [Cu II BCS 2 ] 2- Cu I complex For 3D JSmol movable images see: http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/CuCuI-CuII-L.htm If O 2 free [Cu I BCS 2 ] 3- is the predominant species in soln Cu II complex

9. In Summary: All Three ligands form relatively stable Cu I complexes in the absence of O 2 Me 6 Trien BCA BCS 1.What are the similarities in the 3 complexes? 2.Suggest why the Cu I complexes are “relatively stable” (meaning relative to its Cu II complex under the controlled experimental conditions). 3.Suggest why they are soluble in H 2 O. 4.It turns out for the reaction: Cu I + n L  Cu I L n K f ( Cu I Me 6 Trien ) < K f ( Cu I BCA 2 ) < K f ( Cu I BCS 2 ) Suggest why it is useful to have 3 ligands with 3 differing formation constants. If you had to rationalize the relative order of the formation constants what would you suggest? 5.When oxidized, the Cu II complex of Me 6 Trien has a different geometry than the Cu I complex. Suggest why this occurs with Me 6 Trien but the distortion is less pronounced with BCA or BCS?

10. References and Resources D.K. Johnson, M. J. Stevenson, Z.A. Almadidy, S.E. Jenkins, D. E. Wilcox, N. E. Grossoeheme; “Stabilization of Cu(I) for binding and calorimetric measurements in aqueous solution” Dalton Transactions, 2015 (DOI 10.1039/c5dt02689) A very neat application of the shuttling of the Cu I /Cu II complexes with Me 6 Trien and other ligands is for use in radical polymerization reactions: See G. Kickelbick, T. Pintauerb and K. Matyjaszewski; “Structural comparison of Cu II complexes in atom transfer radical polymerization” New J. Chem, 2002, 26, p. 462-468 (DOI 10.1039/b105454f)