Group 5 — Coordination Chemistry and Molecular Electrochemistry, Synthesis and Catalysis

Group Coordinator: Armando J. L. Pombeiro

Research Guidelines

This Group is mainly directed towards synthesis and catalysis, in fields of Coordination, Inorganic, Bioinorganic, Organometallic and Organic Chemistries. Along the last 3 decades, a significant experience has been gained within the Group on the modes of activation, by coordination, of a variety of small molecules with biological, environmental or industrial significance (such as alkanes, alkynes, phosphaalkynes, isocyanides, dinitrogen, nitriles, cyanamides, nitric oxide, oximes, carbon monoxide, olefins, azides, cyanates, etc.). Attention has recently been paid to apply the accumulated experience on projects with an oriented or applied interest, namely searching for alternatives for industrial processes and new types of molecular activation with significance in fine chemistry.

The main current general scientific aims can be grouped as follows:

i. Syntheses of coordination compounds, also comprehending self-assembly and crystal engineering of metal-organic frameworks (MOFs), polynuclear and supramolecular metal-containing structures;
ii. Molecular activation by coordination to a metal centre and its application in chemical synthesis;
iii. Development of metal-mediated and catalytic processes for the synthesis of functionalized organic compounds with considerable added value and with industrial or pharmacological significance;
iv. Contribution to the understanding of the catalytic biological functions of various metals, namely in the fields of O-transfer to hydrocarbons. The studies can be inspired on biological motifs [e.g. on the actions of the copper particulate methanemonooxygenase (pMMO), the iron MMO, the cytochrome P-450, vanadium peroxidases, nitrile hydratases and nitrogenases] and should be initiated by a preparative stage followed by a reactivity search;
v. Coordination and organometallic chemistry and catalysis in aqueous media;
vi. High pressure gas reactions/catalysis and in supercritical fluids;
vii. Mechanistic studies and DFT calculations applied to selected processes.

Selected Topics

Catalytic Functionalization of Alkanes

Various types of catalysts and systems have been developed for the functionalization of alkanes under mild conditions, namely towards the single-pot syntheses of added value organic compounds e.g. alcohols, ketones, carboxylic acids and organo halides (hydroxylation, oxygenation, carboxylation and halogenation, respectively). Oxidizing agents include dioxygen and hydrogen peroxide (green oxidants), as well as other inorganic or organic peroxides.
The oxidation with peroxides is more effectively achieved in homogeneous or liquid biphasic systems, while the use of dioxygen has been more favourable with supported catalysts.
The most active systems known up-to-date have been achieved by this Group, in particular for the direct conversion of methane into acetic acid and of the other gaseous alkanes into the corresponding carboxylic acids (with TONs approaching twenty thousand). The search for highly active systems in aqueous media is an important current perspective.
Some of the catalytic systems are bioinspired. In fact, in view of the natural occurrence of the multi-copper particulate methane monooxygenase (pMMO, which catalyses the partial oxidation of alkanes), polynuclear Cu compounds (including supramolecular structures and coordination polymers) have been applied as catalysts or catalyst precursors, whereas V- haloperoxidases and Amavadine, a natural V complex with a still unknown biological role (see Group I) have inspired the use of synthetic analogues and other V complexes with N,O-ligands as catalysts for functionalisation.
The work is being developed, in part, with the collaboration of Groups I (Prof. Fraústo da Silva, Dr. J.A.L. Silva, namely the Amavadine and related systems) and III (Prof. A. Palavra, in particular high pressure reactions and syntheses at supercritical conditions).

Metal-mediated syntheses of organic compounds

Metal centres are being applied to the preparation of a wide variety of organic compounds (e.g., oxadiazolines, oxadiazoles, carboxamides, acetylamides, imidoylamidines, iminoisoindolinones, phthalimides, phthalocyanines, cyano-olefins or tetrazoles), by new methods which are advantageous over those based on pure organic chemistry. Some of the reactions can be microwave-assisted. Such types of products have various applications, including of pharmacological interest. The work has been partially developed with the cooperation of Prof. V. Yu. Kukushkin (St. Petersburg St. Univ.).
For instance, we have found a cheap Zn(II)/oxime system, highly active in air and neutral medium, for the preparation of amides (which can be tranquilizers or present antibacterial action) by metal catalysed partial hydrolysis of organonitriles, mimicking the nitrile hydratases function.
Oxadiazolines are other bioactive compounds with antitumor and anti-HIV activity. However, 1,2,4-oxadiazolines are still limited in number and their synthesis and reactivity are little explored. A novel and more convenient synthetic route (which we have patented) consists on the activation (by coordination to Pt) of RCN towards [2+3] cycloadditions with nitrones, a method this Group has been developing. Different types of nitrones, even cyclic ones, as well as other 1,3-dipoles, are being applied to achieve other cycloadditions with nitrile ligands affording a diversity of heterocyclic products. Further studies, involving also the achievement of enantioselectivity, are expected to lead to biologically active heterocycles related to antibiotics or analgesics.
Phthalocyanines, imidoylamidines, phthalimides, iminoisoindolinones and related species have a diversity of applications, and unprecedented preparative methods have been achieved by this Group, based on the reactions of phthalonitriles with an oxime or an hydroxylamine, usually assisted by a metal ion but that can also occur, in some cases, via metal-free processes. The use of a mixed phthalonitriles/ organonitrile reagent allows the synthesis of unsymmetrical imidoylamidines.
Stereoselective synthesis of substituted alkenes is an important aim in organic chemistry and cyano-olefins have been stereoselectively (E isomer) synthesized by reactions of acyclic nitrones with organonitriles (either free or coordinated) bearing an acidic alfa-methylene group.

Coordination compounds with bioactivity

Following our findings that nitriles at Pt(IV) are highly activated towards various types of nucleophiles, a variety of trans-Pt(IV) complexes, related to unconventional Pt compounds known to exhibit antitumor activity, are being prepared with iminoesters, aminooxyimines and many other imine ligands, with different electronic and steric properties. Some of such complexes are expected to act as antitumor agents.
Antitumor diorganotin(IV) complexes are also being synthesized (in cooperation with Prof. Q. Li, Shanxi Medical Univ.) and the redox properties of active Ru complexes with azole-type ligands (collaboration with Prof. B. Keppler, Univ. Vienna) are being investigated by electrochemical methods towards the establishment of relationships of the activity with the structure, the redox potential and the rate of reductively induced chloride ligand loss, features of significance to the understanding of the biological mode of action.

Supramolecular metal-containing structures

Self-assembly synthesis has become an important tool towards the synthesis of a variety of metal-organic frameworks (MOFs), high-nuclearity clusters, coordination polymers and supramolecular networks. Our recently developed self-assembly approach consists in a simple combination, in solution (typically water) and at ambient conditions, of a metal-source, a main chelating ligand, a pH-regulator and an ancillary ligand or spacer. We have thus synthesized a good number of new transition metal complexes of the above types that possess interesting structural, solubility, catalytic, magnetic, host-guest and supramolecular 1D, 2D or 3D features. In particular, various multicopper compounds act as highly efficient catalysts for the mild peroxidative oxidation of alkanes. Besides, the self-assembly synthesis in aqueous medium frequently results in materials, whose matrixes trap various curious water containing clusters or polymeric networks.

Organometallic/Coordination Chemistry in water

The use of water as an unconventional solvent in organometallic chemistry and catalysis, with relevant advantages over the common organic solvents, namely towards the development of "green" systems, has been the object of our interest. Besides the above aqueous media studies of polynuclear and supramolecular metal-containing structures, we have been preparing hydrosoluble coordination compounds with the water soluble phosphine triaza-phosphaadamantane (PTA), or derived ones, for various transition metals, and studying their properties, chemical reactivity and application in catalysis. Such compounds include the first dinitrogen complex (it is a Re compound) and the first copper complex bearing such a type of phosphine.
Water soluble scorpionate compounds with various metals, namely half-sandwich complexes with sulfonated tris(pyrazolylmethane) and related species, have been prepared by this Group and found to act as catalysts for the oxidative functionalization of alkanes. An hydrosoluble Fe complex is active in water as the sole solvent (without needing the presence of any organic solvent) what is of significance towards the establishment of an effective "green" process.

Electrochemical studies

The technique will be applied to the above and other systems, aiming:

i. To investigate their redox properties;
ii. To estimate electrochemical ligand and metal centre parameters which measure their electronic coordinating properties;
iii. To establish redox potential-structure-reactivity relationships;
iv. To activate the systems by electron-transfer (ET) towards further reactivity;
v. To electrosynthesize novel complexes;
vi. To develop electrocatalytic systems by using ET mediators for the oxidation (e.g. alcohols, thiols or unsaturated compounds) or reduction of species that cannot undergo direct redox processes at accessible potentials;
vii. To establish reaction mechanisms (by using unconventional fast cyclic voltammetry and digital simulation methods and stopped-flow kinetics).

Theoretical studies

DFT methods should be applied to representative compounds of the obtained types towards the elucidation of their molecular structures, electronic properties and bonds, the establishment of electronic and structural factors of selected reactions and their mechanisms, on the basis of kinetic and thermodynamic effects, thus contributing to the recognition of structure-activity relationships and to the understanding of the properties and system behaviour.

Selected (recent) Publications

Selected Books

Editor of the book "Trends in Molecular Electrochemistry", A.J.L. Pombeiro (ed.) and C. Amatore (co-ed.), Marcel Dekker / FontisMedia, New York / Lausanne, 2004.

Editor of the book "Molecular Electrochemistry of Inorganic, Bioinorganic and Organometallic Compounds", A.J.L. Pombeiro and J. McCleverty (eds.), NATO ASI Series, Kluwer Academic Publishers, Dordrecht, The Netherlands, 1993.

A.J.L. Pombeiro, "Techniques and Unit Operations in Laboratory Chemistry", (in Portuguese), University Series, Calouste Gulbenkian Foundation, Lisbon, 1983 (1st edition)- 2003 (4th edition).

Papers (ca. 20 selected)

M.V. Kirillova, M.L. Kuznetsov, P.M. Reis, J.A.L. Silva, J.J.R. Fraústo da Silva, A.J.L. Pombeiro*, "Direct and Remarkably Efficient Conversion of Methane into Acetic Acid Catalyzed by Amavadine and Related Vanadium Complexes. A Synthetic and a Theoretical DFT Mechanistic Study", J. Am. Chem. Soc., 2007, 129, 10531-10545.

M.N. Kirillova, A.M. Kirillov, P.M. Reis, J.A.L. Silva, J.J.R. Fraústo da Silva, A.J.L. Pombeiro*, "Group 5-7 Transition Metal Oxides as Efficient Catalysts for Oxidative Functionalization of Alkanes under Mild Conditions", J. Cat., 2007, 248, 130-136.

M.V. Kirillova, J.A.L. da Silva, J.J.R. Fraústo da Silva, A.F. Palavra, A.J.L. Pombeiro*, "Highly Efficient Direct Carboxylation of Propane into Butyric Acids Catalyzed by Vanadium Complexes", Adv. Synth. Cat., 2007, 349, 1765-1774.

T. F. S. Silva , E. C. B. A. Alegria , L.M. D. R. S. Martins, A. J. L. Pombeiro, "Half-sandwich Scorpionate Vanadium, Iron and Copper Complexes: Syntheses and Application in the Catalytic Peroxidative Oxidation of Cyclohexane under Mild Conditioons", Adv. Synth. Cat., in press.

A.J.L. Pombeiro, "Characterization of Coordination Compounds by Electrochemical Parameters", Eur. J. Inorg. Chem., 2007, 1473-1482.

J. Lasri, M.A.J. Charmier*, M. Haukka, A.J.L. Pombeiro*, "Stereospecific Synthesis of Polysubstituted E-Olefins by Reaction of Acyclic Nitrones with Free and Platinum(II) Coordinated Organonitriles", J. Org. Chem., 2007, 72, 750-755.

M.N. Kopylovich, M. Haukka, A.M. Kirillov, V. Yu. Kukushkin, A.J.L. Pombeiro,* "Unsymmetrical NiII - Imidoylamidine Complexes Derived from a Novel Oxime-mediated Single-pot Reaction of Nitriles", Chem. Eur. J., 2007, 13, 786-791.

A.M. Kirillov, M.N. Kopylovich, M.V. Kirillova, M. Haukka, M.F.C. Guedes da Silva and A.J.L. Pombeiro*, "Multinuclear Copper Triethanolamine Complexes as Selective Catalysts for the Peroxidative Oxidation of Alkanes under Mild Conditions", Angew. Chem., Int. Ed., 2005, 44, 4345-4349.

M.N. Kopylovich, V. Yu. Kukushkin*, M. Haukka, K.V. Luzyanin, A.J.L. Pombeiro*, "An Efficient Synthesis of Phthalocyanines Based on an Unprecedented Double-Addition of Oximes to Phthalonitriles", J. Am. Chem. Soc., 2004, 126, 15040-15041.

E. Reisner, V.B. Arion,* M.F.C. Guedes da Silva, R. Lichtenecker, A. Eichinger, B.K. Keppler,* V. Yu. Kukushkin and A.J.L. Pombeiro,* "Tuning of Redox Potentials for the Design of Ruthenium Anticancer Drugs - an Electrochemical Study of [trans-RuCl4L(DMSO)]- and [trans-RuCl4L2]- Complexes, where L = Imidazole, 1,2,4-Triazole, Indazole", Inorg. Chem., 2004, 43, 7083-7093.

Q. Li,* M.F.C. Guedes da Silva and A.J.L. Pombeiro,* "Diorganotin(IV) Derivatives of Substituted Benzohydroxamic Acids with High Antitumor Acticvity", Chem. Eur. J., 2004, 10, 1456-1462.

P.M. Reis, J.A.L. Silva, A.F. Palavra, J.J.R. Fraústo da Silva,* T. Kitamura, Y. Fujiwara, A.J.L. Pombeiro,* "Single-pot Conversion of Methane into Acetic Acid, in the Absence of CO and with Vanadium Catalysts Such as Amavadine", Angew. Chem., Int. Ed.: 2003, 42, 821-823 (highlighted as "hot paper").

S.M.P.R. Cunha, M.F.C. Guedes da Silva and A.J.L. Pombeiro,* "Mixed Dinitrogen- Organocyanamide Complexes of Molybdenum(0) and Their Protic Conversion into Hydrazine and Amidoazavinylidene Derivatives", Inorg. Chem., 2003, 42, 2157-2164.

A.I.F. Venâncio, M.L. Kuznetsov, M.F.C. Guedes da Silva, L.M.D.R.S. Martins, J.J.R. Fraústo da Silva and A.J.L. Pombeiro,* "Metal-Hydride Bond Activation and Metal-Metal Interaction in Dinuclear Iron Complexes with Linking Dinitriles: a Synthetic, Electrochemical and Theoretical Study", Inorg. Chem., 2002, 41, 6456-6467.

V. Yu. Kukushkin*, A.J.L.Pombeiro,* "Additions to Metal-Activated Organonitriles", Chem. Rev., 2002, 102, 1771-1802.

G. Wagner, A.J.L. Pombeiro*, V. Yu. Kukushkin*, "Pt(IV)-Assisted [2+3] Cycloaddition of Nitrones to Coordinated Organonitriles. Synthesis of 4-1,2,4-Oxadiazolines", J. Am. Chem. Soc., 2000, 122, 3106-3111.

A.J.L. Pombeiro,* M.F.C. Guedes da Silva and R.A. Michelin, "Aminocarbyne Complexes Derived from Isocyanides Activated Toward Electrophilic Addition", Coord. Chem. Rev., 2001, 218, 43-74.

R.A. Michelin, A.J.L. Pombeiro,* and M.F.C. Guedes da Silva, "Aminocarbene Complexes Derived from Nucleophilic Addition to Isocyanide Ligands", Coord. Chem. Rev., 2001, 218, 75-112.

A.J.L. Pombeiro,* M.F.C. Guedes da Silva and M.A.N.D.A. Lemos, "Electron-Transfer Induced Isomerizations of Coordination Compounds", Coord. Chem. Rev., 2001, 219-221, 53-80.

P.M. Reis, J.A.L. Silva, J.J.R. Fraústo da Silva and A.J.L. Pombeiro,* "Amavadine as a Catalyst for the Peroxidative Halogenation, Hydroxylation and Oxygenation of Alkanes and Benzene", J. Chem. Soc., Chem. Commun. 2000, 1845-1846.

M.F.C. Guedes da Silva, J.A.L. da Silva, J.J.R. Fraústo da Silva, A.J.L. Pombeiro,* C. Amatore*, J.-N Verpeaux, "Evidence for a Michaelis-Menten Type Mechanism in the Electrocatalytic Oxidation of Mercaptopropionic Acid by an Amavadine Model", J .Am .Chem. Soc., 1996, 118, 7568-7573.

Patents

A.J.L. Pombeiro, J.J.R. Fraústo da Silva, Y. Fujiwara, J.A.L. Silva, P.M. Reis and A.F. Palavra, "Catalysts and Process for the Direct Conversion of Methane into Acetic Acid", PT 102859 (priority date: 2002/10/23; award date: 2004/08/26), WO 2004/037416 A3 (date: 2004/05/06), China (850332MP, date: 2005/06/14), Europe ("Vanadium Catalysts and a Process for the Direct Conversion of Methane into Acetic Acid", 03748820.2-2104-PT0300015), USA ("Process for Direct Conversion of Methane into Acetic Acid", US 7,238,838 B2, award date: 2007/07/03), Japan (2004-546574).

V. Yu. Kukushkin, A.J.L. Pombeiro, G. Wagner and J.J.R. Fraústo da Silva, "Platinum-mediated Synthetic Process for 4-1,2,4-Oxadiazolines", PT 102 483 R (date: 2000/06/21). International Patent pending: PCT/PTO1/00011 (date: 2001/06/21), 01943977.7 (European) and WO 01/98283 A1 (date: 2001/12/27).

A.J.L. Pombeiro, V. Yu. Kukushkin, M.N. Kopylovich and J.J.R. Fraústo da Silva, "Catalyst and Synthetic Process for Carboxamides by Nitrile Hydrolysis", PT 102 618 (priority date: 2001/05/30; award date: 2005/03/08). International Patent pending: WO 02/096856 A1 (date: 2002/12/05).

Q.Li, A.J.L. Pombeiro, M.F.C. Guedes da Silva and H. Lingge, "Diorgano-tin Derivatives of Aryl-hydroxamic Acids Having Anti-tumor Activity", PT 102826 (priority date: 2002/08/07; award date: 2004/08/23).

A.J.L. Pombeiro, M.N. Kopylovich and V. Yu. Kukushkin, "System and Processes for the Syntheses of Imidoylamidines and Acetylamides". PT 103017 X (priority date: 2003/09/05; award date: 2005/06/27).

A.J.L. Pombeiro, M.N. Kopylovich and A.M. Kirillov, "System and Processes for the Catalytic Peroxidative Oxidation, in Mild Conditions, of Cyclohexane and Cyclopentane to the Corresponding Alcohols and Ketones". PT 103033 X (priority date: 2003/10/24; award date: 2005/10/18).

A.J.L. Pombeiro, J.J.R. Fraústo da Silva, J.A.L. Silva, M.V. Kirillova, P.M. Reis, A.F. Palavra and Y. Fujiwara, "Process for the Direct and Simultaneous Conversion of Ethane into Acetic and Propionic Acids". Patent pending 103131 Z (date: 2004/06/02).

A.J.L. Pombeiro, M.N. Kopylovich, V. Yu. Kukushkin and K.V. Louzianine, "Systems and Processes for the Synthesis of Phthalocyanines and Their Complexes, Based on the Use of Oximes or Hydroxylamines, at a Low temperature and with a Good Yield". PT 103130 Y (priority date: 2004/06/02; award date: 2006/03/22).

A.J.L. Pombeiro, A.M. Kirillov, M.N. Kopylovich, M.V. Kirillova, M. Haukka and M.F.C. Guedes da Silva, "New Di-, Tri-, Tetra- and Poly-nuclear Copper Complexes, and Their Use as Catalysts for the Peroxidative Oxidation of Cyclohexane". PT 103225 (priority date: 2005/01/19; award date: 2006/03/20).

A.J.L. Pombeiro, M.V. Kirillova, A.M. Kirillov and J.J.R. Fraústo da Silva, "Methyl(trioxo)rhenium and Other Rhenium Oxides as Catalysts for the Carboxylation and Hydroxylation of Alkanes". PT 103345 (priority date: 2005/09/13; award date: 2006/03/24).

A.J.L. Pombeiro, J.J.R. Fraústo da Silva, J.A.L. Silva, M.V. Kirillova, P.M. Reis, A.M. Kirillov and A. Palavra, "Groups 5 and 6 Metal Oxides as Catalytic Systems for Oxidative Functionalization Reactions of Alkanes". PT 103350 (priority date: 2005/09/16; award date: 2006/03/27).

A.J.L. Pombeiro, J.J.R. Fraústo da Silva, J.A.L. Silva and M.V. Kirillova, "Transition Metal Catalytic Systems for High Turnover Numbers in Alkane Oxidation and Carboxylation Reactions, their Preparation and Utilization". PT 103352 (priority date: 2005/09/20; award date: 2006/08/31).

A.J.L. Pombeiro, M.N. Kopylovich, A.M. Kirillov, V. Yu. Kukushkin and M. Haukka, "Method for the Preparation of New Unsymmetrical Imidoylamidine Nickel(II) Complexes bearing an Isoindolinone Moiety, Compounds thereof and Their Use as Colouring Materials", PT 103522 (priority date: 2006/07/12; award date: 2007/03/30).

A.J.L. Pombeiro, A.M. Kirillov, M.N. Kopylovich, V.N. Kokozay, D.S. Nesterov, "Heterotrimetallic Fe/Cu/Co Complex, Preparation Method Thereof and Catalyst Comprising the Same for the Mild Oxidation of Cycloalkanes", PT 103526 (priority date: 2006/07/14; award date: 2007/05/02).

Q. Li, X. Shang, J. Wu, A.J.L. Pombeiro, "Polymeric Complexes of Dibutyltin and Aryl- hydroximate with Anti-tumor Activity", PT 103613 (priority date: 2006/12/07; award date: 2007/10/03).

A.J.L. Pombeiro, M.V. Kirillova, A.M. Kirillov, J.A.L. Silva, J.J.R. Fraústo da Silva, "Method of Conversion, under Mild Conditions and in Aqueous Medium, of Gaseous and Liquid Alkanes into Carboxylic Acids", PT 103640 (priority date: 2007/01/18; award date: 2007/09/20).

A.J.L. Pombeiro, L.M.D.R.S. Martins, E.C.B.A. Alegria, "Use of Microwaves for the Synthesis of Substituted Tris(pyrazolyl)methanes", PT 103934 (priority date: 2008/01/18), patent pending.

A.J.L. Pombeiro, K.V. Luzyanin, V. Yu. Kukushkin, M.N. Kopylovich, "Method of 3- Iminoisoindolin-1-ones Synthesis Based on the Use of N,N-diethylhydroxylamine", PT 103718 (priority date: 2007/04/13; award date: 2007/10/03).

A.J.L. Pombeiro, L.M.D.R.S. Martins, E.C.B.A. Alegria, M.V. Kirillova, "New Complexes of Rhenium with Pyrazole or tris(1-pyrazolyl)methanes and Their Application as Catalysts for the Partial Oxidation, under Mild Conditions, of Ethane to Acetic and Acetaldehyde and of Cyclohexane to Cyclohexanol and Cyclohexanone", PT 103735 (priority date: 2007/05/11).

A.J.L. Pombeiro, M.V. Kirillova, J.A.L. Silva, J.J.R. Fraústo da Silva, "System for the Conversion, under Mild Conditions, of Ethane and Propane in Carboxylic Acids by Using Vanadium-containing Heteropolyacid Catalysts", PT 103814 (priority date: 2007/08/23).

A.J.L. Pombeiro, J. Lasri, M.A.J. Charmier, M. Haukka, "System and Method of Synthesis of Polysubstituted E-cyanolefins Based on Reactions of Nitriles with Nitrones", PT 103888 (priority date: 2007/11/20).