Radu Silaghi-Dumitrescu

 

 

SMALL MOLECULE ACTIVATION BY metalloproteins and related systems

 

 

Our main research interest is currently in small molecule activation by biological metal centers, with emphasis on hemes and hemoproteins, using computational chemistry as well as experimental methods. Hemes, i.e., complexes of iron with protoporphyrin IX and its derivatives, have been some of the most studied prosthetic groups in biochemistry. This has been due to their spectroscopic accessibility, as well as to their ubiquitous involvement in processes central to life (e.g. energy transport, energy storage, respiration, defence mechanisms). See here a general overview of structures and functions for hemes and heme proteins in biology. Besides hemes, other biological/biomimetic systems of interest for us have been non-heme iron, copper, and cobalt centers.

 

 

Research projects:

 

Computational:

  • Nitric oxide reduction by cytochrome P450 nitric oxide reductase (P450NOR)
  • Nitric oxide reduction by non-heme iron systems (FprA, a novel class of nitric oxide reductases)
  • Nitrite reduction by nitrite reductases and related model systems, and the role of linkage isomerism therein
  • Activation of molecular oxygen and of peroxides by hemoproteins and by non-heme iron systems (e.g., peroxidases, heme oxygenase, cytochrome P450, bleomycin, Rieske dioxygenases)
  • Bioorganometallic chemistry with hemoproteins
  • Superoxide detoxification by superoxide reductases and superoxide dismutases
  • The nature and reactivity of less common iron oxidation states, e.g. Fe(IV), Fe(I)
  • Electromerism in adducts of transition metals with diatomic ligands (e.g., nitric oxide, dioxygen, superoxide, peroxide)
  • Excited-state properties from ground-state computations (collaboration with Dr. Svistunenko, University of Essex)
  • Nitrile hydration by nitrile hydratases
  • Halogen activation by metalloproteins

 

Experimental:

  • Biotransformations using horseradish peroxidase (peroxidase/peroxygenase/oxidase reactions)
  • Nitrite linkage isomerism in hemoproteins and model complexes
  • The nature of transient complexes involved in oxygen-oxygen bond activation in hemoproteins (ferrous-dioxygen, ferric-(hydroperoxo), ferryl)
  • Peroxynitrite and its adducts with hemoproteins and related systems

 

Participation in projects led elsewhere:

  • At the University of Georgia (under Prof. Kurtz): Experimental studies on non-heme iron proteins involved in oxidative and nitrosative stress: FprA / flavorubredoxin (a novel class of nitric oxide reductases), rubrerythrin and nigerythrin (a novel class of peroxidases), rubredoxin (electron transfer). These have involved a wide range of methods, from molecular biology to protein crystallography, Mosbauer spectroscopy, stopped-flow kinetics and computational chemistry.
  • At the University of Essex (under Profs. Cooper and Wilson): Studies on the reactivity of hemoglobin and myoglobin towards oxidative and nitrosative stress; blood substitutes

 

 

 

Relevant research publications:

 

50. Svistunenko, Dimitri A.; Reeder, Brandon J.; Wankasi, Mieebi M.; Silaghi-Dumitrescu, Radu; Cooper, Chris E. Rinaldo, Serena; Cutruzzolà, Francesca; Wilson, Michael T. Interaction of Aplysia limacina metmyoglobin with hydrogen peroxide.  Dalton Transactions, (2007), 10.1039/b615770j.

 

49. Silaghi-Dumitrescu, Radu; Reeder, Brandon; Nicholls, Peter; Cooper, Chris E.; Wilson, Michael T. Ferryl haem protonation gates peroxidatic reactivity in globins.  Biochemical Journal, (2007), 10.1042/BJ20061421.

 

48. Schwartz, Jennifer K.; Liu XF; Albetel AN; Silaghi-Dumitrescu, Radu, Kurtz,  Donald M, Jr.; Theil, Elizabeth C; Solomon, Edward I; Structure/function correlations in binuclear non-heme ferrous sites: Specific characterization of the active sites in m-Ferritin and nitric oxide reductases    Abstracts of Papers, 231st ACS National Meeting, United States, March 26, 2006  (2006),     INOR-89

 

47. Silaghi-Dumitrescu, Radu. Hemes Revisited by Density Functional Approaches. 2. A Paradigm for Axial Ligation In Hemoproteins.    Studia Universitatis Babes-Bolyai, Chemia (2006),  in press.

 

46. Silaghi-Dumitrescu, Radu. Fe(IV)-Fe(II) electromerism in hemoprotein complexes: implications for ferryl chemistry.    Proc.  Rom. Acad. Series B (2006),  in press.

 

45. Silaghi-Dumitrescu, Radu; Silaghi-Dumitrescu, Ioan; Editorial – special issue on Computational Inorganic Chemistry.  Chemtracts – Inorganic Chemistry (2005), 50, 11-16.

 

44. Silaghi-Dumitrescu, Radu; Silaghi-Dumitrescu, Ioan; Computational Inorganic Chemistry – a useful tool, and more.  Chemtracts – Inorganic Chemistry (2005), 684-708.

 

43. Isaza, Clara E.; Silaghi-Dumitrescu, Radu; Iyer, Ramesh B.; Kurtz, Donald M. Jr.; Chan, Michael K. Structural Basis for O2 Sensing by the Hemerythrin-like Domain of a Bacterial Chemotaxis Protein: Substrate Tunnel and Fluxional N Terminus.   Biochemistry, (2006), 45(30), 9023-9031.

 

42. Dunne, Jacqueline; Caron, Alexis; Menu, Patrick; Alayash, Abdu I.; Buehler, Paul W.; Wilson, Michael T.; Silaghi-Dumitrescu, Radu; Faivre, Beatrice; Cooper, Chris E. Ascorbate removes key precursors to oxidative damage by cell free hemoglobin in vitro and in vivo.  Biochemical Journal, (2006), 399(3), 513-24.

 

41. Silaghi-Dumitrescu, Radu; Copper-containing nitrite reductase: a DFT study of nitrite and nitric oxide adducts.  Journal of Inorganic Biochemistry, (2006), 100(3), 396-402.

 

40. Silaghi-Dumitrescu, Radu; Silaghi-Dumitrescu, Ioan; DFT and the electromerism in complexes of iron with diatomic ligands.  Journal of Inorganic Biochemistry, (2006), 100(1), 161-166.

 

39. Silaghi-Dumitrescu, Radu; Cooper, Chris E., Transient species involved in catalytic dioxygen/peroxide activation by hemoproteins: possible involvement of protonated compound I species.  Dalton Transactions, (2005), 3477-3482.

 

38. Iyer, Ramesh B.; Silaghi-Dumitrescu, Radu; Lanzilotta, William N.; Kurtz, Donald M.  Novel non-heme diiron bacterial peroxidases.    Abstracts of Papers, 229th ACS National Meeting, San Diego, CA, United States, March 13-17, 2005  (2005),     INOR-556

 

37. Iyer, Ramesh,* Silaghi-Dumitrescu, Radu,* Lanzilotta, William N. Kurtz, Donald M. Jr.  High-resolution crystal structures of Desulfovibrio vulgaris (Hildenborough) nigerythrin: facile, redox-dependent iron movement, domain interface variability, and peroxidase activity in the rubrerythrins   J. Biol. Inorg. Chem. (2005), 10, 407-416. (*authors marked “contributed equally to this work”)

 

36. Silaghi-Dumitrescu, Radu, Kurtz, Donald M. Jr., Ljungdahl,| Lars G., Lanzilotta, William N.  X-ray Crystal Structures of Moorella thermoacetica FprA. Novel Diiron Site Structure and Mechanistic Insights into a Scavenging Nitric OxideReductase.   Biochemistry, (2005), 44(17), 6492-6501.

 

35. Silaghi-Dumitrescu, Radu. A density functional study of heme-peroxynitrite adducts.  J. Mol. Struct. THEOCHEM, (2005), 722, 233-237.

 

34. Silaghi-Dumitrescu, Radu. “High-valent” ferryl-oxo complexes: how “high” are they really?    Studia Universitatis Babes-Bolyai, Chemia (2005),  50, 17-21.

 

33. Silaghi-Dumitrescu, Radu. Discontinuum between ferrous-superoxo and ferric-peroxo in heme [FeO2]9 complexes?    Studia Universitatis Babes-Bolyai, Chemia (2005),  in press.

 

32. Silaghi-Dumitrescu, Radu. Nitrile hydration by the cobalt-containing nitrile hydratase. DFT investigation of the mechanism    Revista de Chimie  (2005), 56(4), 359-362.

 

31. Silaghi-Dumitrescu, Radu; Ng, Kim Yong; Viswanathan, Rathinam, Kurtz, Donald M. Jr. A Flavo-diiron protein from Desulfovibrio vulgaris with oxidase and nitric oxide reductase activities. Evidence for an In vivo nitric oxide scavenging function.  Biochemistry, (2005), 44(9), 3572-9.

 

30. Das, Amaresh; Silaghi-Dumitrescu, Radu; Ljungdahl, Lars G.; Kurtz, Donald M., Jr., Cytochrome bd oxidase, oxidative stress and dioxygen tolerance of the strictly anaerobic bacterium, Moorella thermoacetica.  Journal of Bacteriology, (2005), 187(6), 2020-2029.

 

29. Kurtz, Donald M.; Lanzilotta, William N.; Silaghi-Dumitrescu, Radu.  How microbes detoxify superoxide, hydrogen peroxide, and nitric oxide: The non-heme iron reductive paradigm.    Abstracts of Papers, 227th ACS National Meeting, Anaheim, CA, United States, March 28-April 1, 2004  (2004),     INOR-418

 

28. Silaghi-Dumitrescu, Radu. Factors controlling O-O bond cleavage in ferric-hydroperoxo complexes.    Proc.  Rom. Acad. Series B, (2004), 3, 155-163.

 

27. Silaghi-Dumitrescu, Radu. Bioorganometallic complexes relevant to the “push effect” in hemoproteins.    Proc.  Rom. Acad. Series B, (2004), 3, 149-154.

 

26. Silaghi-Dumitrescu, Radu. Bonding in ferric-oxo complexes.    Studia Universitatis Babes-Bolyai, Chemia (2004),  49(2), 235-240.

 

25. Silaghi-Dumitrescu, Radu; Linkage isomerism in nitrite reduction by cytochrome cd1 nitrite reductase.  Inorganic Chemistry (2004), 43(12), 3715-3718.

 

24. Silaghi-Dumitrescu, Radu; The nature of the “high-valent” complexes in the catalytic cycles of hemoproteins.  Journal of Biological Inorganic Chemistry (2004), 9, 471-476.

 

23. Silaghi-Dumitrescu, Radu; The nitric oxide adducts of cytochrome cd1 nitrite reductase.    Revista de Chimie  (2004), 55, 496-498.

 

22. Silaghi-Dumitrescu, Radu; On the performance of the PM3 semiempirical method with heme complexes relevant to dioxygen and peroxide activation.    Revista de Chimie (2004), 55, 304-307.

 

21. Silaghi-Dumitrescu, Radu; Heme ferrous-hydroperoxo complexes: some theoretical considerations.    Archives of Biochemistry and Biophysics (2004), 424, 137-140.

 

20. Silaghi-Dumitrescu, Radu; Silaghi-Dumitrescu, Ioan. Hemes revisited by density functional approaches. 1. The axial ligand and the dioxygen-peroxo chemistry.    Revue Roumaine de Chimie (2004), 3-4, 257-268.

 

19. Silaghi-Dumitrescu, Radu; Amthor, Stephan; Paizs, Csaba; Majdik, Cornelia; Tosa, Monica; Moldovan, Paula; Sas, Angela; Tamas, Liana;  Irimie, Florin-Dan. Horseradish peroxidase - catalyzed oxidation of water - insoluble phenothiazines.    Studia Universitatis Babes-Bolyai, Chemia (2003),  48, 165.

 

18. Kurtz, Donald M., Jr.;  Emerson, Joseph P; Silaghi-Dumitrescu, Radu; Kung, Irene; Das, Amaresh; Ljungdahl, Lars; How microbes detoxify superoxide, hydrogen peroxide and nitric oxide. The non-heme iron reductive paradigm     Journal of Inorganic Biochemistry (2003),  96, 69.

 

17. Kurtz, Donald M., Jr.;  Silaghi-Dumitrescu, Radu; Das, Amaresh; Jameson, Guy; Ljungdahl, Lars; Huynh, Boi Hanh  A non-heme iron nitric oxide reductase that protects against nitrosative stress in acetogenic bacteria             Journal of Inorganic Biochemistry  (2003),  96, 174.

 

16. Silaghi-Dumitrescu, Radu; Kurtz, Donald M., Jr.  High-resolution crystal structures and spectroscopy of native and Compound I Cytochrome c Peroxidase        Chemtracts – Inorganic Chemistry (2003), 16, 722-728 – Commentary.

 

15. Silaghi-Dumitrescu, Radu; Irimie, Florin-Dan; Paizs, Csaba; Majdik, Cornelia; Tosa, Monica; Moldovan, Paula; Sas, Angela; Tamas, Liana.  Horseradish peroxidase catalyzed oxidation of some benzyl-type alcohols.    Studia Universitatis Babes-Bolyai, Chemia  (2003),  48, 177-182.

 

14. Silaghi-Dumitrescu, Radu; Kurtz, Donald M., Jr.  Tuning the electronic structure of octahedral iron complexes {FeL(X)} (L = 1-alkyl-4,7-bis(4-tert-butyl-2-mercaptobenzyl)-1,4,7-triazacyclononane, X = Cl, CH3O, CN, NO): the S = 1/2 - S = 3/2 spin equilibrium of {FeLPr(NO)}.    Chemtracts – Inorganic Chemistry (2003), 16(8), 468-473 – Commentary.

 

13. Silaghi-Dumitrescu, Radu.  Nitric oxide reduction by heme-thiolate enzymes (P450nor): A reevaluation of the mechanism.    European Journal of Inorganic Chemistry (2003),   (6), 1048-1052.

 

12. Silaghi-Dumitrescu, Radu; Coulter, Eric D.; Das, Amaresh; Ljungdahl, Lars G.; Jameson, Guy N. L.; Huynh, Boi Hanh; Kurtz, Donald M., Jr.  A flavodiiron protein and high molecular weight rubredoxin from Moorella thermoacetica with nitric oxide reductase activity.    Biochemistry (2003), 42(10),  2806-2815.

 

11. Silaghi-Dumitrescu, Radu; Silaghi-Dumitrescu, Ioan; Coulter, Eric D.; Kurtz, Donald M., Jr.  Computational study of the non-heme iron active site in superoxide reductase and its reaction with superoxide.    Inorganic Chemistry (2003), 42(2), 446-456.

 

10.Silaghi-Dumitrescu, Luminita; Silaghi-Dumitrescu, Radu; Blake, Alexander J; Cooke, Paul A.; Sowerby, D. Bryan, Chlorination of (AsPh2)2O: Supramolecular structure of dihydroxodiphenylarsonium hydrogensulfate [AsPh2(OH)2] [HOSO3], Revue Roumaine de Chimie (2002), 47(10-11), 1063-1068.

 

9. Irimie, Florin-Dan; Paizs, Csaba; Majdik, Cornelia; Tosa, Monica; Misca, Radu; Silaghi-Dumitrescu, Radu.  Bioorganic synthesis of some (5-benzothiazol-2-yl-furan-2-yl)-methanols in cell catalysis using Saccharomyces cerevisiae.    Heterocyclic Communications (2002), 8(5), 489-492.

 

8. Silaghi-Dumitrescu, Radu; Silaghi-Dumitrescu, Ioan; Coulter, Eric D.; Emerson, Joseph P; Kurtz, Donald M., Jr.  Computational study of the non-heme iron active site in superoxide reductase and its reaction with superoxide.    Journal of Inorganic Biochemistry (2001), 86(1), 432.

 

7. Silaghi-Dumitrescu, Luminita; Silaghi-Dumitrescu, Ioan; Silaghi-Dumitrescu, Radu; Haiduc, Ionel; Blake, Alexander J.; Sowerby, D. Bryan.  Bromination of (AsPh2)2O: the structure of tribromo-diphenylarsenic(V).    Revista de la Sociedad Quimica de Mexico (2000), 44(2), 134-138.

 

6. Irimie, Florin-Dan; Paisz, Csaba; Joo, Francisc; Silaghi-Dumitrescu, Radu; Tosa, Monica; Majdik, Cornelia.  Biocatalytical reduction of some 5-(carboxyethyl-phenyl)-furyl-2-carboxaldehydes mediated by baker's yeast.    Progress in Catalysis (1999), 8(2), 70-73.

 

5. Irimie, Florin-Dan; Paizs, Csaba; Joo, Francisc; Silaghi-Dumitrescu, Radu; Tosa, Monica; Majdik, Cornelia.  Bioorganic reduction of some 5-phenyl-furyl-2-carboxaldehydes mediated by bakers' yeast.    Roumanian Biotechnological Letters (1999), 4(1), 71-74.

 

4. Irimie, Florin-Dan; Paizs, Csaba; Silaghi-Dumitrescu, Radu; Damian, G.; Majdik, Cornelia; Tosa, Monica.  Mass spectrometry of some new 2-hydroxymethyl-5-phenyl-furans obtained through cell catalysis.    Studia Universitatis Babes-Bolyai, Chemia (1998),  43(1-2),  173-177.

 

3. Majdik, Cornelia; Irimie, Florin-Dan; Paizs, Csaba; Silaghi-Dumitrescu, Radu; Joo, Francisc; Tosa, Monica.  Synthesis and reduction of some nitro-benzofurans.    Studia Universitatis Babes-Bolyai, Chemia (1998), 43(1-2), 115-120.

 

2. Irimie, Florin-Dan; Paizs, Csaba; Chender, C.; Joo, Francisc; Silaghi-Dumitrescu, Radu; Majdik, Cornelia; Tosa, Monica.  Furyl-benzothiazoles. Synthesis and reactivity.    Studia Universitatis Babes-Bolyai, Chemia (1998), 43(1-2), 109-114.

 

1. Silaghi-Dumitrescu, Radu; Paisz, Csaba; Irimie, Florin-Dan; Joo, Francisc; Majdik, Cornelia; Tosa, Monica.  Biotransformation of nitroso naphthols bioassisted by Baker's yeast.    Studia Universitatis Babes-Bolyai, Chemia (1998), 43(1-2),  83-90.

 

Book:

Radu Silaghi-Dumitrescu, Horseradish peroxidase – a versatile catalyst

2006, Research Signpost, India

 

Publication on the World Wide Web:

HRP: A Summary of its Structure, Mechanism and Substrate Diversity - International Working Group on Plant Peroxidases (IWGPP)

http://www.unige.ch/LABPV/perox.html

 

 

Links:

Romanian institutions:

The ‘Babes-Bolyai’ University

The Romanian Academy

 

Romanian chemistry/biochemistry journals

Studia Universitatis Babes-Bolyai

Revista de Chimie

Revue Roumaine de Chimie

Proceedings of the Romanian Academy