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Organic and Organometallic Chemistry


The team has been working for many years in the area of main group organometallic chemistry and this work continues with the objective of providing useful synthetic methodologies, transition-metal homogeneous catalysis, catalysis by metal nanoparticles, and organic synthetic routes to dendrimers, bioactive molecules and functional compounds by conventional or high energy techniques.

The activities may be classified as follows:

1.   New Synthetic Methodologies
2.   Transition Metal Catalysis in Organic Synthesis
3.   Organic Chromophores
4.   Biologically Active Compounds
5.   Dendrimer Chemistry



Research Staff
Dr. Barry Steele, Researcher A'
Dr. George Heropoulos, Researcher A'
Dr. Ioannis Kostas, Researcher A'

Researchers Emeriti
Dr. Constantinos Screttas

Dr. Maria Micha-Screttas

Scientific Technical Staff
Cecile Arbez-Gindre, PhD
Georgia Antonopoulou, PhD

Post-doctoral Fellows
Dr. Spyros Georgakopoulos
Dr. Alia Cristina Tenchiu

Post-graduate Researchers
Ioannis Stamatopoulos

Undergraduate students
Iro Ventouri
Georgia Dasi


Current Research Activities

1. New Synthetic Methodologies

Novel Main-Group Organometallic Reactions
Bulky Aromatic Molecules / Improved Routes to Organolithium Reagents
The research of the Organic and Organometallic Chemistry Group has always had a strong emphasis on main group organometallic chemistry, and one of the areas which has been developed in the last years involves the use of metal alkoxides for modifying reactivity and properties of the more traditional organometallic reagents such as those of lithium, sodium, potassium and magnesium. Recent work has centered on the superbase system butyllithium-lithium potassium bis(dimethylaminoethoxide). This provides a catalytic route for the efficient preparation of over 40 new bulky aromatic hydrocarbons, phenols, anilines, heterocycles. Derivatisation of these leads to many more compounds. Such bulky molecules find applications in many areas of chemistry, e.g. for the stabilisation of molecules with unusual oxidation states or with novel types of bonding, for the preparation of stable homoleptic materials and as ligands for homogeneous catalysis.


Application of Non-Conventional Techniques (Microwaves & Ultrasound)
Non-conventional techniques, such as ultrasound and microwaves, are becoming increasingly important tools for the organic chemist and have been used in our group since 2005 (COST Action D32 and Marie Curie “Sopholides”). Compared to classical heating methods, higher yields can be obtained, reaction times are decreased and better selectivities are observed. MW techniques are based on the absorption of microwave energy by dielectric materials. Ultrasound effects are based on the cavitation effect, whereby the implosion of very short-lived microbubbles can generate temperatures up to 10000°C, and pressures up to 100 atm. 
Current Research

  • Ultrasound assistance of reactions with sterically crowded compounds.

          Ultrasound:  93 %  in  15 min vs Conventional Heating: 77 %  in  20 hours.
  • Microwave-promoted Suzuki–Miyaura cross-coupling of aryl halides with phenylboronic acid under aerobic conditions. No reaction with conventional heating.

  • Synthesis and studies in the field of dendrimers, cyclodextrins.
  • Use of solid additives to promote microwave-assisted reactions of otherwise non-reactive compounds.
  • “Sonication switching”: Ring substitution with US and Side-chain substitution with MW.
  • Novel dual frequency ultrasound application in synthesis.
  • Solvent-free synthesis of 4-substituted coumarins.


Recent publications

  • I.D. Kostas, G. A. Heropoulos, D. Kovala-Demertzi, P. N. Yadav, J. P. Jasinski, M. A. Demertzis, F. J. Andreadaki, G. Vo-Thanh, A. Petit and A. Loupy, Tetrahedron Lett.,  2006, 47, (26), 4403-4407,.“Microwave-promoted Suzuki-Miyaura cross-coupling of aryl halides with phenylboronic acid under aerobic conditions catalyzed by a new palladium complex with a thiosemicarbazone ligand”
  • G. A Heropoulos, G. Cravotto, C. G. Screttas and B. R. Steele, Tetrahedron Lett., 2007, 48, (18), 3247-3250,. “Contrasting chemoselectivities in the ultrasound and microwave assisted bromination reactions of substituted alkylaromatics with N-bromosuccinimide”
  • F. Wiesbrock, C. Patteux, T. K. Olszewski, A. Blanrue, G. A. Heropoulos, B. R. Steele, M. Micha-Screttas, T. Calogeropoulou, Eur. J. Org. Chem. 2008, 4344-4349. “Solution-Phase Synthesis and Scale-Up of 1st Generation Tetraester-Dendritic Branches Involving Microwave Irradiation and/or Ultrasound”
  • S. Aime, E. Gianolio, F. Arena, A. Barge, K. Martina, G. A. Heropoulos and G. Cravotto, Org. Biomol. Chem., 2009, 7, (2), 370-379,. “New cyclodextrin dimers and trimers capable of forming supramolecular adducts with shape-specific ligands”
  • C. G. Screttas, B. R. Steele, M. Micha-Screttas, G. A. Heropoulos, Org. Lett., 2012, 14, 5680–5683, “Aryllithiums with Increasing Steric Crowding and Lipophilicity Prepared from Chlorides in Diethyl Ether. The First Directly Prepared Room-Temperature-Stable Dilithioarenes”
  • G. Cravotto, K. Martina, M. Caporaso, G. Heropoulos, L. Jicsinszky, 2012 MRS Fall Meeting, Boston 25-30 Nov. 2012, MRS Online Proceedings Library, 2013, 1492, 177-182 doi: 10.1557/opl.2013.176, Cambridge University Press, “Highly efficient Synthesis of per-substituted amino-cyclodextrins under Microwave Irradiation in a closed Cavity”
  • K. C. Prousis, N. Avlonitis, G. A. Heropoulos and T. Calogeropoulou, Ultrason. Sonochem., 2014, DOI:10.1016/j.ultsonch.2013.10.018, “FeCl3-catalysed ultrasonic-assisted, solvent-free synthesis of 4-substituted coumarins. A useful, complement to the Pechmann reaction”
  • V. J. Sinanoglou, P. Zoumpoulakis, G. Heropoulos, C. Proestos, A. Ciric, J. Petrovic, J. Glamoclija and M. Sokovic, J. Food Sci. Technol., 2014 (accepted for publication), “Lipid and fatty acid profile of the edible fungus Laetiporus sulphurous. Antifungal and antibacterial properties”


2. Transition Metal Catalysis in Organic Synthesis

Transition Metal Homogeneous Catalysis

Our investigations include the development of transition-metal (e.g. Ru, Rh, Pd, Pt) complexes with novel ligands and their evaluation as catalysts in reactions of enormous academic and industrial interest, such as hydroformylation, hydrogenation, coupling reactions (Heck, Suzuki). More specifically, our research activities include:

(a) Catalysis by hybrid and hemilabile phosphorus ligands (e.g. phosphines, phosphine oxides, phosphinites, mixed phosphine-phosphinites) possessing additional potent donors such as oxygen, nitrogen, sulfur (e.g. I, II, III).


Recent publications

  • I.D. Kostas* “Recent Advances in P,N-Containing Ligands for Transition-Metal Homogeneous Catalysis”. In Advances in Organic Synthesis, Atta-ur-Rahman, FRS (Ed.), Bentham Science, 2013, Vol. 6, pp. 3-58. Invited book chapter
  • K.A. Chatziapostolou, K.A. Vallianatou, A. Grigoropoulos, C.P. Raptopoulou, A. Terzis, I.D. Kostas*, P. Kyritsis*, G. Pneumatikakis J. Organomet. Chem. 2007, 692 (19), 4129-4138 “Synthesis and characterization of new RhI complexes bearing CO, PPh3 and chelating P,O- or Se,Se-ligands. Application to hydroformylation of styrene”
  • E.I. Tolis, K.A. Vallianatou, F.J. Andreadaki, I.D. Kostas* Appl. Organomet. Chem. 2006, 20 (5), 335-337 “A new rhodium complex with a nitrogen-containing bis(phosphine oxide) ligand as an efficient catalyst for the hydroformylation of styrene”

(b) Catalysis in air by phosphane-free ligands such as thiosemicarbazones (e.g. IV) and chalcogen-containing Schiff bases (e.g. V). For the first time, we used thiosemicarbazones as catalyst precursors for palladium-catalyzed coupling reactions (Heck, Suzuki), under aerobic conditions, and one of our Pd complexes is currently commercially available by SIGMA-ALDRICH (Product No.: 674125) and other companies.


Recent publications

  • I.D. Kostas*, F.J. Andreadaki, D. Kovala-Demertzi*, C. Prentjas, M.A. Demertzis Tetrahedron Lett. 2005, 46 (12), 1967-1970 “Suzuki-Miyaura cross-coupling reaction of aryl bromides and chlorides with phenylboronic acid under aerobic conditions catalyzed by palladium complexes with thiosemicarbazone ligands”
  • I.D. Kostas*, B.R. Steele*, A. Terzis, S.V. Amosova, A.V. Martynov, N.A. Makhaeva Eur. J. Inorg. Chem. 2006, (13), 2642-2646 “New Palladium Complexes with S- or Se-Containing Schiff-Base Ligands as Efficient Catalysts for the Suzuki-Miyaura Cross-Coupling Reaction of Aryl Bromides with Phenylboronic Acid under Aerobic Conditions”

(c) Asymmetric catalysis with new chiral amino diphosphite, phosphonite, phosphite-phoephoramidite and phosphine-phosphoramidite ligands, such as Me-AnilaPhos (IV) as a highly efficient ligand for the rhodium-catalyzed enantioselective olefin hydrogenation; selected comments: (a) “excellent catalyst” (a critical review: L. Eberhardt, D. Armspach, J. Harrowfield, D. Matt Chem. Soc. Rev. 2008, 37, 839); (b) “highly versatile ligand class” (ALDRICH: D. Amoroso et al. Aldrichimica Acta, 2008, 41, 20).


Recent publications

  • K.A. Vallianatou, D.J. Frank, G. Antonopoulou, S. Georgakopoulos, E. Siapi, M. Zervou, I.D. Kostas* Tetrahedron Lett. 2013, 54 (5), 397-401 “Rhodium-catalyzed asymmetric olefin hydrogenation by easily accessible aniline- and pyridine-derived chiral phosphites”
  • I.D. Kostas*, K.A. Vallianatou, J. Holz, A. Börner* Tetrahedron Lett. 2008, 49 (2), 331-334 “A new easily accessible chiral phosphite-phosphoramidite ligand based on 2-anilinoethanol and R-BINOL moieties for Rh-catalyzed asymmetric olefin hydrogenation”
  • I.D. Kostas*, K.A. Vallianatou, J. Holz, A. Börner Appl. Organomet. Chem. 2005, 19 (10), 1090-1095 “Rhodium complexes with a new chiral nitrogen-containing BINOL-based diphosphite or phosphonite ligand: synthesis and application to hydroformylation of styrene and/or hydrogenation of prochiral olefins”


(d) Catalysis by high energy techniques such as a microwave irradiation. This technique was used to the Suzuki coupling in air, catalyzed by a palladium complex with a thiosemicarbazone ligand (XII), totally inactive under conventional heating.

Recent publication

  • I.D. Kostas*, G.A. Heropoulos*, D. Kovala-Demertzi*, P.N. Yadav, J.P. Jasinski, M.A. Demertzis, F.J. Andreadaki, G. Vo-Thanh, A. Petit, A. Loupy Tetrahedron Lett. 2006, 47 (26), 4403-4407 “Microwave-promoted Suzuki-Miyaura cross-coupling of aryl halides with phenylboronic acid under aerobic conditions catalyzed by a new palladium complex with a thiosemicarbazone ligand”

(e) Aqueous catalysis offering environmental benefits and also the advantage of recycling and reusing the catalyst. We have published the first study concerning the evaluation of air-stable and water-soluble metalloporphyrins (XIII) in the Suzuki reaction and also the selective hydrogenation of unsaturated aldehydes in neat water or in aqueous/organic biphasic system, respectively. The catalysts could be easily recycled and reused.

Recent publications

  • C. Stangel, G. Charalambidis, V. Varda, A.G. Coutsolelos,* I.D. Kostas* Eur. J. Inorg. Chem. 2011, (30), 4709-4716 “Aqueous–Organic Biphasic Hydrogenation of trans-Cinnamaldehyde Catalyzed by Rhodium and Ruthenium Phosphane-Free Porphyrin Complexes”
  • I.D. Kostas*, A.G. Coutsolelos*, G. Charalambidis, A. Skondra Tetrahedron Lett. 2007, 48 (38), 6688-6691 “The first use of porphyrins as catalysts in cross-coupling reactions: a water-soluble palladium complex with a porphyrin ligand as an efficient catalyst precursor or the Suzuki–Miyaura reaction in aqueous media under aerobic conditions”


Catalysis by Metal Nanoparticles

We have synthesized metal nanoparticles (NPs) such as thiosemicarbazone-stabilised Pd NPs and Pt NPs using 3,3´-thiodipropionic acid as a protective agent that found to be efficient catalysts for the Suzuki reaction and the selective hydrogenation of trans-cinnamaldehyde, respectively. The nanocatalysts could be recovered and reused.


Recent publications

  • Pournara, D. Kovala-Demertzi*, N. Kourkoumelis, S. Georgakopoulos, I.D. Kostas* Catal. Commun. 2014, 43, 57-60 “Platinum/3,3´-thiodipropionic acid nanoparticles as recyclable catalysts for the selective hydrogenation of trans-cinnamaldehyde”
  • D. Kovala-Demertzi*, N. Kourkoumelis*, K. Derlat, J. Michalak, F.J. Andreadaki, I.D. Kostas* Inorg. Chim. Acta 2008, 361 (5), 1562-1565 “Thiosemicarbazone-derivatised palladium nanoparticles as efficient catalyst for the Suzuki-Miyaura cross-coupling of aryl bromides with phenylboronic acid”


3. Organic Chromophores

The application of the expertise of the group to the synthesis of organic and organometallic compounds with potential materials applications is focused in the areas of Nonlinear optical materials and Near Infrared dyes.

Organometallic Near Infrared Dyes
Previous work from the Organic and Organometallic Chemistry Group has been concerned with the preparation of organic nonlinear optical materials. Certain of these with ferrocenyl substituents were observed to have substantial first hyperpolarisability values and also to have significant absorption in the near infrared (NIR) region.
Current interest in NIR absorbing dyes arises from their many potential applications such as:

  • Fluorescence sensing applications for effective, fast and accurate routine analysis of biological samples. Few species in a biological sample matrix fluoresce in the NIR, thereby reducing their interference. Applications include on-line fibre-optic biosensors, DNA sequencing, DNA chips, protein detection, immunoassays etc. This has particular importance in in vivo applications where the concentration of potentially toxic diagnostic reagents can be minimised.


  • Detection and treatment of cancer. A non-invasive imaging technology allows the detection of tumours using NIR optical spectroscopy and molecular tumour recognition techniques while photodynamic therapy involves the activation of prelocalised chemicals with light. NIR dyes act as photosensitisers and thereby effect the conversion of oxygen to the reactive singlet state.
  • In analytical chemistry, NIR dyes find potential applications as pH detectors, as well as detectors of metal ions, anions, and environmental pollutants.
  • Applications in optical recording, thermal displays, xerography, laser printers, laser filters, etc.

The increasing demand of NIR dyes in many different fields makes further active research towards more efficient and economical materials highly desirable. With our experience in main-group organometallic chemistry as a starting point we are developing the chemistry of ferrocene-based NIR dyes and are combining this also with our activities in dendrimer chemistry.

1st hyperpolarisability: 1700•10-30   esu (2.64 •10-6 M)
λNIR (loge): 1080 (4.5)


λNIR carbocation (loge): 989 (3.44) Highly stable carbocation; λNIR (loge): 900 (4.2)

Recent publications

  • C. Arbez-Gindre, B.R. Steele, G.A. Heropoulos, C.G. Screttas, J.-E. Communal, W.J. Blau and I. Ledoux-Rak, J. Organomet. Chem. 2005, 690, 1620-26“A facile organolithiumroute to ferrocene-based triarylmethyl dyes with substantial near IR and NLO properties”
  • C. Villalonga-Barber, K. Vallianatou , S. Georgakopoulos, B. R. Steele , M. Micha-Screttas , E. Levin , N. G. Lemcoff, Tetrahedron, 2013, 69, 3885-3895. “Synthesis, characterisation, electronic spectra and electrochemical investigation of ferrocenyl-terminated dendrimers”


4. Biologically Active Compounds

Neuroprotective Stilbene Derivatives
Resveratrol is well-known naturally occurring compound with anti-oxidant and other properties. We have prepared and evaluated analogues with increased lipophilicity and modified structural characteristics.
Taking advantage of our main-group organometallic methodologies, resveratrol derivatives were prepared and assessed for their neuroprotective ability.

Metal Chelators
Synthesis and study of derivatives with nitrogen- or chalcogen containing donors. These compounds serve as hemi-labile ligands in certain transition metal complexes which are studies for their potential catalytic activity in, for example, hydroformylation and carbon-carbon coupling reactions. More recently, we have been studying new metal chelators for their biogical activity. Many metals play an important biological role but, in some cases, their overexpression or accumulation can cause problems. Iron and copper, for example, are directly implicated in mechanisms leading to oxidative stress which, in turn, is a key factor involved in the development of age-related disorders such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Friedreich’s ataxia. We have prepared aromatic hydrazones with varying degrees of alkyl substitution, size and lipophilicity and their metal complexes. The chelators are currently being assessed in silico and in vitro for their potential biological activity.



Recent publications

  • G. Skretas, A. Meligova, C. Villalonga-Barber, D. J. Mitsiou, M. N. Alexis, M. Micha-Screttas, B. R. Steele, C. G. Screttas, D. W. Wood, J. Am. Chem. Soc., 2007, 129, 8443-57. “Engineered chimeric enzymes as tools for drug discovery:Generating reliable bacterial screens for the detection, discovery and assessment of estrogen receptor modulators”
  • C. Villalonga-Barber, A. K. Meligova, X. Alexi, B. R. Steele, C. E. Kouzinos, C. G. Screttas, E. S. Katsanou, M. Micha-Screttas, M. N. Alexis, Bioorg. Med. Chem. 2011, 19, 339-351. "New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription”
  • C. Koukoulitsa, S. Durdagi, E. Siapi, C. Villalonga-Barber, X. Alexi, B. R. Steele, M. Micha-Screttas, M. N. Alexis, T. Mavromoustakos, Eur. Biophys. J. 2011, 40, 865–875. “Comparison of themal effects of stilbenoid analogs in lipid bilayers using differential scanning calorimetry and molecular dynamics. Correlation of their thermal effects and topographical position with antioxidant activity”.

Patent: Micha-Screttas, Villalonga Barber, Steele, Alexis, GR 1005435, 2006


Glucopyranosyl-modified thiosemicarbazones
The project includes the synthesis of bioactive organic and organometallic compounds and investigation of their bioactivity. For instance, we synthesized a series of β-D-glucopyranosyl-modified thiosemicarbazones, which were found to be inhibitors of glycogen phosphorylase, a target for the design of type 2 diabetes therapeutics, and also as anticancer agents.

Recent publications

  • K.-M. Alexacou, A.-C. Tenchiu (Deleanu), E.D. Chrysina, M.-D. Charavgi, I.D. Kostas*, S.E. Zografos, N.G. Oikonomakos, D.D. Leonidas* Bioorg. Med. Chem. 2010, 18 (22), 7911-7922 “The binding of β-d-glucopyranosyl-thiosemicarbazone derivatives to glycogen phosphorylase: A new class of inhibitors”


5. Dendrimer Chemistry

Dendrimer Chemistry is a rapidly expanding field with many potential applications such as for drug-delivery systems, as "light harvesters" and as macromolecular homogeneous catalysts.
Drug delivery is of utmost importance when designing drug formulations because the delivery device is responsible, to a large extent, for the bioavailability, targeting and toxicity of the bioactive compound. Dendrimers, due to their controllable size and monodispersity, can act as excellent carriers for a wide range of molecules, which can be encapsulated in the interior of the dendrimer or interact with the dendrimer’s terminal groups.
Targeting groups, imaging agents, solubilising groups can be attached to the periphery

Our group has been involved in the design and synthesis of new dendritic molecules, using biocompatible compounds as building units, for the encapsulation of anti-cancer drugs. In particular, modular “click chemistry” synthetic methodologies have been developed for the preparation of a number of polyhydroxy dendrimeric and glycodendrimeric compounds. The glycodendritic compounds have been studied for their binding affinity with lectins using thermodynamic and crystallographic methods.
Also, dendrimer-liposome complex nanoparticles have been studied as drug delivery systems. Such systems can show improved pharmacokinetics over those involving dendrimer or liposome only.

Organometallic NIR dye dendrimers
Based on related work in our group on NLO materials and NIR dyes, we are now engaged in the synthesis of related materials with ferrocene-based NIR chromophores on the periphery of polyether dendrimers.

Recent publications

  • I.D. Kostas, F.J. Andreadaki, E.A. Medlycott, G.S. Hanan, E. Monflier Tetrahedron Lett. 2009, 50 (16), 1851-1854 “Synthesis of a halo-methylphenylene periphery-functionalized triazine-based dendritic molecule with a 3,3´-dimethyl-biphenyl linker using tris(halo-methylphenylene)triazines as building blocks”
  • K. Gardikis, S. Hatziantoniou, M. Bucos, D. Fessas, M. Signorelli, T. Felekis, M. Zervou, C.G. Screttas, B.R. Steele, M. Ionov, M. Micha-Screttas, B. Klajnert, M. Bryszewska, C. Demetzos J. Pharm. Sci. 2010, 99, 3561-3571. “New drug delivery nanosystem combining liposomal and dendrimeric technology (liposomal locked-in dendrimers) for cancer therapy”
  • K. Gardikis; S. Hatziantoniou; M. Signorelli; M. Pusceddu; M. Micha-Screttas; A. Schiraldi; C. Demetzos; D. Fessas, Colloids and Surfaces B: Biointerfaces 2010, 81, 11-19. “Thermodynamic and structural characterization of Liposomal-Locked in-Dendrimers as drug carriers”.
  • C. Villalonga-Barber, K. Vallianatou, S. Georgakopoulos, B. R. Steele, M. Micha-Screttas, E. Levin , N. G. Lemcoff, Tetrahedron, 2013, 69, 3885-3895. “Synthesis, characterisation, electronic spectra and electrochemical investigation of ferrocenyl-terminated dendrimers”







National Hellenic Research Foundation (NHRF), 48 Vassileos Constantinou Ave., 11635 Athens, Greece, Tel. +302107273700, Fax. +302107246618