Patrick J. Desrochers Associate Professor Department of Chemistry University of Central Arkansas Conway, AR 72035 (501) 450-5939 (501) 450-3623 FAX patrickd@uca.edu

Current Research Interests · promoting undergraduate research · phosphine nickel cysteine complexes · chalcogen selectivity by nickel · atypical nickel-cysteine centers · reversible alkylation of nickel-cysteine centers · monomeric nickel-borohydride · electronically modified Tp*

Publications

* "Bis[hydrotris(4-chloro-3,5-dimethylpyrazolyl)borato]nickel(II)" Desrochers, P. J.; Brown, J. R.; Arvin, M. E.; Jones, G. D.; Vicic, D. A. Acta Cryst. 2005, E61, m1455–m1458.

* "A Stable Monomeric Nickel-Borohydride" Desrochers, P.J.; LeLievre, S.; Johnson, R.; Lamb. B.; Phelps, A. L.; Cordes, A.W.; Gu, W.; Cramer, S. P.  Inorg. Chem. 2003, 42, 7945.

* "Characteristics of Five Coordinate Nickel-Cysteine Centers" Desrochers, P. J.; Cutts, R. W.; Rice, P. K.; Golden, M. L.; Graham, J. B.; Barclay,T. M.; Cordes, A. W. Inorg. Chem. 1999 38, 5690.

---

Undergraduate Research

• opportunities in the UCA College of Natural Sciences & Mathematics
• Current student research chalk-talk signup and schedule
• CUR-sponsored undergraduate researcher database, to be used by grad schools to find skilled BS students
• Council on Undergraduate Research (CUR)
• National Conference on Undergraduate Research (NCUR)

---

Water Soluble Phosphine Nickel Cysteine complexes

Selective nickel-cysteine binding on a heterogeneous support

Desrochers, P. J.; Winkler, S. A.; Hong, B.; Brown, J. R.; Tarkka, R. M.; Holman, G.; Richardson, C. B.

Department of Chemistry, University of Central Arkansas, Conway AR 72035

Submitted to the the 229th National Meeting of the American Chemical Society, San Diego, March 2005.

Cysteine is in the active sites of numerous metalloproteins, and its metal affinity can also contribute to the cytotoxicity of these elements. This laboratory has described factors controlling the geometry adopted by cysteine and nickel. Selective nickel-cysteine interactions will be described, now with a cysteine peptide anchored to a heterogeneous polystyrene gel support. The discrimination of nickel(II) between cysteine, homocysteine, and methionine is observed. Spectroscopic measurements show that properly ligated nickel(II) binds gel-supported cysteine in trigonal bipyramidal and square planar geometries identical to solution phase analogues. Newly reported here are diamagnetic water soluble square planar complexes [dppeNi^IICysX]Cl. CysX represents cysteine, cysteine ethyl ester, cysteamine, and selenocysteamine. These results will extend observations for nickel-cysteine small molecules to larger protein systems. The cysteine/homocysteine discrimination and accompanying color change with nickel binding are also being investigated as a selective potential detection method for these amino acids in complex matrices.  

---

Chalcogen Selectivity by Nickel Controls Coordination Geometries in Model Biochemical Systems
Desrochers, P. J.*; Abrams, M. L.; Nutt, D. L.; Arvin, M. E.; Phelps, A. L. Department of Chemistry, University of Central Arkansas, Conway AR 72035
20th International Symposium on the Organic Chemistry of Sulfur, Flagstaff, AZ  July 2002

Cysteine,[1] selenocysteine,[2] and thioethers[3] are essential chalcogen-donors and substrates for three of the four known classes of nickel enzymes.  Complementary theoretical and experimental results show that nickel’s discrimination  between chalcogen-donor amino acids determines its coordination geometries in model biochemical systems.  Kinetically stable trigonal bipyramidal geometries are obtained for sulfur- and selenium-donor amino acid residues (Cys); comparable oxygen donors (Ser) yield square pyramidal geometries.   The complete series of five coordinate complexes, Tp*Ni(E,N), will be described, where Tp* = the facial anionic chelate hydrotris(3,5-dimethylpyrazolyl)borate, and E = O, S, and Se.  Trigonal bipyramidal geometries observed for sulfur and selenium spectroscopically match structurally characterized complexes involving
cysteine and its ethyl ester.[4]  Optimal equatorial-plane pi overlap stabilizes Tp*Ni(S,N) and Tp*Ni(Se,N).  Alkylation or oxidation of these complexes reduces this pi overlap, resulting in loss of the trigonal bipyramidal geometry.  Accordingly, the thioether methionine does not coordinate nickel in this system.  Alkylation, but not oxidation, is reversible, and oxidation of the selenium form is considerably faster than its sulfur derivative.  The square pyramidal geometry obtained for oxygen is confirmed by comparative spectroscopic measurements with Tp*Ni(acac) and published nickel-acac complexes.[5]  Oxygen’s diminished pi overlap with nickel prevents ethanolamine from stabilizing the trigonal bipyramidal geometry.  These results have implications for the role of cysteine in nickel-hydrogenase and carbon monoxide dehydrogenase enzymes as well as cysteine-targeted toxicity of this metal.

[1] Volbeda, A.; Charon, M. -H.; Piras, C.; Hatchiklan, E. C.; Frey, M.; Fontecilla-Camps, J. C. Nature, 1995, 373, 580.
[2]  Wang, C.; Franco, R.; Moura, J. J. G.; Moura, I.; Day, E. P. J. Biol. Chem. 1992, 267, 7378.
[3]  Dobbek, H.; Svetlitchnyi, V.; Gremer, L.; Huber, R.; Meyer, O. Science, 2001, 293, 1281.
[4]  Desrochers, P. J.; Cutts, R. W.; Rice, P. K.; Golden, M. L.; Graham, J. B.; Barclay,T. M.; Cordes; A. W. Inorg. Chem., 1999; 38, 5690.
[5]  Hammes, B. S.; Carrano, C. J. Inorg. Chem.1999, 38, 3562.

---

Atypical Nickel-Cysteine Centers

Cysteine and related derivatives like cystine, homocysteine, and methionine are amino acids important to bioinorganic chemistry.¹ The sulfur of these residues can serve as a redox center, a nucleophile, a determinant of protein structure, a Bronsted base, or a Lewis base for binding metal ions.² Cysteine-metal ion binding can be more general, as in cysteine-rich metallothioneins whose roles include scavenging excess essential metals or sequestering potentially toxic metals. This binding can also be highly specialized, as in the cube shaped iron-sulfur clusters that serve as relay points in numerous biochemical electron transfer processes. For some metals, binding to cysteine-sulfur in a distinct protein environment encourages chemistry rarely observed in synthetic systems.

Nickel(II) usually binds cysteine and related derivatives in square planar geometries, a classic d⁸ characteristic, outside of structured protein environments.³ Cysteine invariably binds nickel using :NH₂ and :SR donor groups in synthetic complexes. This square planar geometry is conserved in simple peptide complexes, where nickel binds either terminal -NH₂ or internal amide -NH- centers to achieve N,S coordination.⁴ Distorted five coordinate nickel-cysteine  geometries are found in [NiFe]-hydrogenases, bacterial enzymes that reversibly catalyze the reaction, 2H⁺ + 2e- = H₂ .⁵ If atypical nickel-cysteine coordination is an essential feature of nickel in proteins, then synthetic nickel-cysteine complexes that resist square planar geometries will help explain this coordination in proteins.

The trio of metal ions, cobalt(II), nickel(II), and copper(II), are common diagnostic substitutes for each other (Ni⁺² or Co⁺² for Cu⁺² in blue copper proteins)⁶ or for other essential metals in cysteine protein environments (ie., for zinc(II) in zinc fingers⁷or for iron(II) in rubredoxins⁸). Spectroscopic and magnetic differences introduced by one metal versus another have helped describe metal-binding centers in proteins. Substitution often retains the native structure of the coordination pocket about the metal, despite each metal ion's unique coordination preferences.

1. Lippard, S. J.; Berg, J. M. Principles of Bioinorganic Chemistry, Mill Valley, CA: University Science Books, 1994, pp. 45-46.
2. Gui, Z.; Green, A. R.; Kasrai, M.; Bancroft, G. M.; Stillman, M. J.Inorg. Chem. 1996, 35, 6520.
3. (a) Baidya, N.; Ndreu, D.; Olmstead, M. M.; Mascharak, P. K. Inorg. Chem. 1991, 30, 2448. (b) Nair, M. S.; Arasu, P. T.; Pillai, M. S.; Natarajan, C. Trans. Met. Chem. 1995, 20, 132.
4. (a) Kozlowski, H.; Decock-Le Reverend, B.; Ficheux, D.; Loucheux, C.; Sovago, I. J. Inorg. Biochem. 1987, 29, 187. (b) Panossian, R.; Asso, M.; Guiliano, M. Spectroscopy Letters 1983, 16, 463.
5. (a) Volbeda, A.; Charon, M. -H.; Piras, C.; Hatchiklan, E. C.; Frey, M.; Fontecilla-Camps, J. C. Nature 1995, 373, 580. (b) Volbeda, A.; Garcin, E.; Piras, C.; de Lacey, A. L.; Fernandez, V. M.; Hatchikian, E. C.; Frey, M.; Fontecilla-Camps, J. C. J. Am. Chem. Soc. 1996, 118 , 12989.
6. (a) Fernandez, C. O.; Sannazzaro, A. I.; Diaz, L. E.; Vila, A. J. Inorg. Chim. Acta 1998, 273 , 367. (b) Vila, A. J.; Fernandez, C. O. J. Am. Chem. Soc. 1996, 118 , 7291.
7. Xu, Y.; Wilcox, D. E. J. Am. Chem. Soc. 1998, 120 , 7375.
8. Huang, Y. -H.; Moura, I.; Moura, J. J. G.; LeGall, J.; Park, J. -B.; Adams, M. W. W.; Johnson, M. K. Inorg. Chem. 1993, 32, 406.

Five coordinate nickel-cysteine complexes (Tp^XNiCysY) have been synthesized in our laboratory.*  These models provide electronically tunable tris(pyrazolyl)borate pockets, ideal for studying electronic factors affecting nickel-cysteine centers.  A key question to be answered by this work is how the trigonal bipyramidal Tp^XNiCysY geometry encourages electronic communication between Tp^X and the nickel-cysteine fragment.  Experimental and theoretical work in our laboratory uses these models to electronically influence the oxidation and alkylation of an atypical nickel-cysteine center.

---

Alkylation, Dealkylation of Nickel-Cysteine Centers

A poster of this work was presented at the 219th National Meeting of the American Chemical Society,
San Francisco, March 2000.

OVERCOMING THE KINETIC STABILITY OF A NICKEL-CYSTEINE CENTER BY ALKYLATION.

Andrea L. Phelps and Patrick J. Desrochers*  Dept. of Chemistry, Univ. of Central Arkansas, Conway, 72035.

Monomeric five coordinate nickel-cysteine centers can be isolated using tris(pyrazolyl)borate ligands.  These systems are a departure from the common square planar geometries that predominate in other nickel-cysteine synthetic complexes.  An emerging characteristic of these complexes is a kinetic stability that precludes the binding of additional Lewis bases to nickel. Alkylation of the cysteine-sulfur center has proven to be a successful method for encouraging the nickel center to accommodate additional Lewis bases.  The alkylated form readily binds coordinating solvents, yielding six coordinate nickel centers; this characteristic is absent in the un-alkylated five coordinate precursor.  This "switch" induced by alkylation is reversible; de-alkylation returns the more inert five coordinate precursor.  Possible extensions to metal-protein centers, and ligand modifications to test the extent of the above chemistry will be discussed.

---

Monomeric Nickel-Borohydrides

We have synthesized and crystallographically characterized a monomeric nickel-borohydride complex. This complex reduces halocarbons, while the nickel center recovers the displaced halide.  Nickel-borides have been recognized for their value as heterogeneous catalysts in organic syntheses.*   We are investigating the mechanism of reactivity of our soluble nickel-borohydride.

        *Ganem, B.; Osby, J. O. Chem. Rev. 1986, 86, 763.

The following abstract summarizes a presentation of this work at the joint Southeast/Southwest Regional Am. Chem. Society meeting in New Orleans, LA  December 2000.

THE REACTIVITY OF A MONOMERIC NICKEL-BOROHYDRIDE, THE HYDRIDE BULLET.
Galloway, R. J.;   Phelps, A. L.; Desrochers, P. J.;
Department of Chemistry, University of Central Arkansas, Conway, AR   72035

We have uncovered a monomeric transition metal borohydride, Tp*Ni(H₃B-H).  This compound has potential in the short term for insights it should provide on halocarbon (possibly fluorocarbon) reductions mediated by transition metals .  Preliminary results for the reaction
               Tp*Ni(H₃B-H)  +   R-X    ->   Tp*Ni-X    +    R-H    +    H₂ + B?
indicate a reaction rate that is dependent on both [Tp*Ni(H₃B-H)] and [R-X], implying an overall second order rate law.  A pronounced deuterium isotope effect has been observed in these measurements, indicating rate limiting hydride transfer may be central to this reaction. Even more exciting is the potential this borohydride compound may hold for hydrocarbon activation mechanisms. Methane and borohydride are isoelectronic and isostructural.
Characteristics and reactivity of Tp*Ni(H₃B-H) may be extrapolated to Tp*Ni(H₃C-R) or
hydrocarbons in general.

---

Electronically Modified Tp*

The nickel center of our principle model, Tp*NiCysEt, mediates communication between the chelating Tp* and CysEt ligands.  The electronically tunable tris(pyrazolylborate) pocket is expected to allow us to study the electronic factors influencing the oxidation and alkylation of our nickel-cysteine center.  We believe that the trigonal bipyramidal geometry of our model system is a key factor in this chemistry.

Go to Mike's Pyrazole Place

---

This research is financially supported by the American Chemical Society's Petroleum Research Fund, the Arkansas Science Information Liaison Office, and the University of Central Arkansas Research Council.