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 April 18, 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/.

M 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) d8 forms a tetrahedral complex: Not a Square Planar Complex M Pt(II) distorts to avoid tetrahedral coordination NiIIdmpI2 The 2,9-dimethyl-1,10-phenanthroline (dmp) ligand is sufficiently sterically hindered that it can block the d8 Ni(II) ion from forming a square planar complex either with a second dmp ligand or with two halide ligands. The Pt(II) metal distorts the ligand (see the movable 3D images posted with Jsmol) so that the dmp is no longer completely planar and also distorts its own bonding angle to the dmp to maintain a slightly distorted square planar coordination geometry. Question for Students: Why does d8 want to have a square planar geometry and why is the driving force for Pt(II) to form a square planar complex larger than that for Ni(II)? PtIIdmpI2 For all 3D JSmol movable images addressed in this LO see: http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/LigandsFavoringTetrahedralGeometry.htm

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.

Measure Thermodynamics of Cu(I) binding to the protein in question Cu(I)-protein Apo-protein Desired Experiment Measure Thermodynamics of Cu(I) binding to the protein in question Cu(I)Ln + + nL Experimental Challenge Solution Cu(I) salts tend to be insoluble Find a ligand that will create a soluble Cu(I)Ln complex Other species in solution (H2O, Buffer, Anions, etc) compete for the Cu(I) Find a ligand that will bind more strongly than H2O, Buffer, Anions etc) Cu(I)Ln complexes can disproportionate to form Cu(0) and Cu(II)Ln species 2CuILn ⇌ Cu(0) + CuIILn Find a ligand that forms a relatively stable CuILn complex to disfavor the disproportion reaction Cu(I) complexes can be oxidized in the presence of O2 CuILn + O2  CuIILn Again use a ligand that forms a relatively stable CuILn complex However most importantly, work in an O2 free environment Some of the keys words here are “relatively”…so for example when we say “Find a ligand that forms a relatively stable CuILn complex to disfavor the disproportion reaction”, “relatively” is relative to the Cu(II) complex.

Ligand 1: Me6Trien 2CuIL + Cu(0) + CuIIL2+ CuIMe6Trien will not disproportionate 2CuIL + Cu(0) + CuIIL2+ And in fact: the reverse comproportion reaction is the preferred preparation method CuII + Cu(0) + excess Me6Trien 2 CuIL+ in O2 The Cu(I) will oxidize to Cu(II) and will pick up an additional L: anion or solvent Questions for Students: What is the geometry about Cu in the Cu(I)L complex? Is this a favorable geometry for the given d electron count? Is this (the geometry of the Cu(I) complex) a favorable geometry for Cu(II)? What is the geometry about the Cu(II) metal center in the oxidized form Cu(II)L? Note you may need to go to the 3D images to examine the geometry If O2 free CuIL is the predominant Species in solution For 3D JSmol movable images see: http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/LigandsFavoringTetrahedralGeometry.htm

Ligand 2: BCA 2[CuIBCA2]3- Cu(0) + [CuIIBCA2]2- CuI complex [CuIBCA2]3-will not disproportionate 2[CuIBCA2]3- Cu(0) + [CuIIBCA2]2- CuI complex CuII complex The CuII 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 in O2 Questions for Students: What is the geometry about Cu in the Cu(I)L complex? Is this a favorable geometry for the given d electron count? Is this (the geometry of the Cu(I) complex) a favorable geometry for Cu(II)? What is the geometry about the Cu(II) metal center in the oxidized form Cu(II)L? Note you may need to go to the 3D images to examine the geometry If O2 free [CuIBCA2]3- is the predominant species in soln For 3D JSmol movable images see: http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/LigandsFavoringTetrahedralGeometry.htm

Ligand 3: BCS 2[CuIBCS2]3- Cu(0) + [CuIIBCS2]2- CuI complex [CuIBCS2]3-will not disproportionate 2[CuIBCS2]3- Cu(0) + [CuIIBCS2]2- CuI complex CuII complex in O2 Again, the same questions for students: What is the geometry about Cu in the Cu(I)L complex? Is this a favorable geometry for the given d electron count? Is this (the geometry of the Cu(I) complex) a favorable geometry for Cu(II)? What is the geometry about the Cu(II) metal center in the oxidized form Cu(II)L? Note you may need to go to the 3D images to examine the geometry If O2 free [CuIBCS2]3- is the predominant species in soln For 3D JSmol movable images see: http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/LigandsFavoringTetrahedralGeometry.htm

In Summary: All Three ligands form relatively stable CuI complexes in the absence of O2 What are the similarities in the 3 complexes? Suggest why the CuI complexes are “relatively stable” (meaning relative to its CuII complex under the controlled experimental conditions). Suggest why they are soluble in H2O. It turns out for the reaction: CuI + n L  CuILn Kf(CuIMe6Trien) < Kf(CuIBCA2) < Kf(CuIBCS2) 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? When oxidized, the CuII complex of Me6Trien has a different geometry than the CuI complex. Suggest why this occurs with Me6Trien but the distortion is less pronounced with BCA or BCS? Me6Trien BCA Start with the easy examples BCA: The CuI(BCA)2: Structure is very close to tetrahedral and d10 and tetrahedral is a good geometry for this d electron count. Why is it somewhat air stable? If you had to predict the geometry of a generic CuII(bindentate-L)2 complex what would you predict? The only structure found in the CCDC is with one BCA type (no carboxylates) ligand and two Cl ligands and is a Distorted Tetrahedron!! Not a great geometry for Cu(II): Why? Cu(II) will Jahn-Teller distort therefore tetrahedral geometry is not favorable for Cu(II). Square planar, Square pyramidal and Tetragonally distorted octahedral complexes are good geometries for Cu(II). Ask the students to draw a simple LFT diagram for each (or find the diagrams in their textbook or notes: see HouseCroft and Sharpe , Inorganic Chemistry, 3rd Edition, Page 648, Figure 21.11 for an excellent Figure of LFT diagrams). BSC: Same as BCA But here there is a structure for the Cu(II)(BCS analog)2 complex which also has a distorted tetrahedral structure. For 3D movable images see http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/CuIBCs2CuIIBCS2.html Me6Trien: The CuIMe6Trien complex is hard to see in 2D. See http://www.people.carleton.edu/~mcass/1-Inorganic-C351/jsmol/CuI-CuII-Me6Trien.html. The Cu(I) structure is clearly a distorted tetrahedron and when oxidized to Cu(II), the metal picks up a fifth ligand (a solvent molecule or anion from solution) and changes geometry! Tetrahedral geometry is not favorable for Cu(II). Square planar, Square pyramidal and tetragonally distorted octahedral complexes are good geometries for Cu(II). Again ask the students why? The next question is why do the Cu(II) complexes of the BCA and BCS complexes have a distorted tetrahedral geometry and that of the Me6Trien ligand is not a distorted tetrahedron? Next, these are solid state structures, how do we know what is going on in solution? BCS

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, Vol 44, Issue 37, p. 16494-16505 (DOI 10.1039/c5dt02689) A very neat application of the shuttling of the CuI/CuII complexes with Me6Trien and other ligands is for use in radical polymerization reactions: See G. Kickelbick, T. Pintauerb and K. Matyjaszewski; “Structural comparison of CuII complexes in atom transfer radical polymerization” New J. Chem, 2002, 26, p. 462-468 (DOI 10.1039/b105454f)