06.3. Rudjer Boskovic Institute Division for Organic-chemistry & Biochemistry Laboratory for Supramolecular and Nucleoside Chemistry Related to the Business Plan 1. Fundamental research Research activities of the Laboratory for the next 2 years are defined by the project “Supramolecular organization in gels, molecular recognition and catalysis” (project No:00980503) accepted by Croatian Ministry of Science and Technology for financial support in 2002-2004 period. The experimental research defined by the project closely relates to contemporary issues of high scientific interest such as non-covalent intermolecular interactions in synthetic and natural systems and design of new functional molecules and materials of nano- and micrometer scale dimensions. The specific aims are: 1. to reveal new facts relevant for better understanding of supramolecular organisation, in particular the one in organogels based on unidirectional selfassembly of small organic molecules into gel fibres of nanometer thickness and micrometer length; 2. to provide the specific knowledge that would open the possibility for accurate design of controlled gelation systems capable of responding to internal or external stimuli (light, temperature, pH, selected solute) in particular of photo-controlled gels based on gelator molecules with photoisomerisable units; 3. to provide the specific knowledge necessary for design of controlled gelation systems with possible application as sensors or drug delivery systems; 4. to design molecules capable of binding and recognition of nucleotides in water, and of recognition of specific structural motifs of nucleic acids (single stranded regions, hairpins, bulges) and their potential use as specific markers or gene manipulation tools; 4. to investigate further possible applications of new supramolecular organometallic catalysts designed previously at IRB for selected enantioselective transformations of high synthetic interest. For additional 3 years period, the more intensive approach to nano-sized organic functional materials could be envisioned if the necessary condition of availability of specific equipment (TEM, SEM, AFM, STM) for this type of research would be fulfilled. The outlined basic research should result by publication of cca 40 –50 high quality scientific papers in recognised international journals during the next 5 years period. 2. Education -supervision and education of diploma, Msc and PhD students: -At present, 3 graduate, 2 MSc and 3 PhD students of University of Zagreb and - shared supervision of 2 PhD students from Department of Analytical Chemistry of the Faculty of Natural Sciences, University of Zagreb - for the next 3 years period education and supervision of additional 2-3 graduate, 2-3 MSc and 2-3 PhD students could be estimated -courses delivered at postgraduate level of organic chemistry studies at University of Zagreb: 1. Organic Stereochemistry; 2. Supramolecular chemistry 3. Nuceosides and Nucleic Acids - Prof. M. Žinić, Head of organic chemistry postgraduate studies at Faculty of Natural Sciences of University of Zagreb -organization of basic NMR course in collaboration with RBI NMR Center with practical work on Varian Gemini 300 MHz instrument is planned to start in 2003. The courses will be delivered for undergraduate and postgraduate students of chemistry, biochemistry, pharmacy, chemical technology and biotechnology of University of Zagreb. 3. Technology development and support - At present two projects under negotiation with PLIVA comp. Details not available due to confidentiality agreement. Estimated income 50 000 – 70 000 Euro. - European patent “Synthesis of the Sulfonylpyrimidine Derivatives with Anticancer Activity (Pat. Appl. 98108370.2-2101) will be granted until January 2003. The domestic and international licensing possibilities or selling of patent property will be investigated. Mladen Žinić -Curriculum vitae Born: Education: 1971 1974 1978 1947 Zagreb B.Sc. Chem.; Faculty of Technology, University of Zagreb M.Sc. Chem., Univ. of Zagreb Ph.D. Org. chem.; Univ. of Zagreb Research Positions: 1974 - 1982 teaching assistant, Dept. of Organic Chem. Faculty of Pharmacy, Univ. of Zagreb 1977 - 1978 1982 - 1985 postdoctoral fellow with Prof. Vlado Prelog, ETH, Zürich senior res. chem.; R&D, BELUPO Pharm. Comp. 1985 - Rudjer Bošković Institute, Dept. of Organic chemistry& Biochemistry 1993 Rank of senior res. associate and Head of the Laboratory of Supramolecular and Nucleoside Chemistry, Rudjer Bošković Institute 1998 Rank of senior scientist 1999 Titled full professor of chemistry, Faculty of Science, University of Zagreb Research interest: Supramolecular chemistry, molecular recognition of nucleotides, amino acids and metal cations, DNA-intercalation and recognition, molecular self-assembly processes in gels, supramolecular organometallic catalysis. Teaching: Organic Stereochemistry and Supramolecular Chemistry at the Postgraduate studies of Chemistry, University of Zagreb Head of Organic Chemistry Postgraduate Studies, Univ. of Zagreb Research Projects: “Synthetic Molecular Receptors for Nucleo bases, Ncleosides and Nucleotides” European Community Commission, CI 1*/ 0523, (J.-M. Lehn project coordinator), 1989 1991. Design and Synthesis of Supramolecular Systems” Croatian Ministry of Science and Technology 1997-2001 – principal researcher “DNA Interactions with new Aromatic Compounds” DLR Bonn, Germany in collaboration with Prof. Dr. H.-J- Schneider, Saarlandes University, Sarbrücken, Germany. 1997-99. “Non-covalent Interactions with Aromatic Compounds in Natural and Synthetic Systems, Deutsche Forschungsgemeinshaft (DFG), Germany, 436 KRO 113/3/0, in collaboration with Prof. Dr. H.-J- Schneider, Saarlandes University, Saarbrücken, Germany. 2000. –2001. ECC-COST-D11, Supramolecular Chemistry, “Low Molecular Weight Gelators of Organic Fluids and Water” 2000. – 2003. “Supramolecular Organization in Gels. Molecular Recognition and Catalysis” Croatian Ministry of Science and Technology – principal researcher 2002-2004. Memberships: Member of the Scientific Council of Natural Sciences of the Croatian Ministry of Science and Technology President of the Scientific Council, Division of Chemistry, Rudjer Bošković Institute Member of the Swiss Chemical Society Member of the Croatian Chemical Society Member of the Editorial Board of the Journal of Physical Organic Chemistry 2003.Member of the list of referees for: Journal of the American Chemical Society; Chemistry A European Journal; Journal Of Physical Organic Chemistry Member of the Organizing Committee of the 13th European Symposium on Organic Chemistry, September, 10-15, 2003, Cavtat, Croatia Awards: National Award for Science 2001. List of publications 2000-2002 37. In Vitro Cytotoxicity of Three 4,9-Diazapyrenium Hydrogensulphate Derivatives on Different Human Tumor Cell Lines. S. Roknić, Lj. Glavaš-Obrovac, I. Karner, I. Piantanida, M. Žinić, K. Pavelić, and J. Pavelić, Chemotherapy, 46, 143-149, 2000. 38. 4,9-Diazapyrenium Cations. Synthesis, Physisco-chemical Properties and Binding of Nucleotides in Water. I. Piantanida, V. Tomišić, and M. Žinić, J. Chem. Soc., Perkin Trans. 2, 375-383, 2000. 39. The Interaction of New 4,9-Diazapyrenium Compounds with Double Stranded Nucleic Acids. B. S. Palm, I. Piantanida, M. Žinić, and H.-J. Schneider, J. Chem. Soc., Perkin Trans. 2, 385-392, 2000. 40. Remarkable Cumulative Stereoselectivity in Cyclopropanation with Supramolecular Cu(I) Catalytic Complexes. T. Portada, M. Roje, Z. Raza, V. Čaplar, M. Žinić, and V. Šunjić, J. Chem. Soc., Chem. Commun., 1993-1994, 2000. 41. Calix4arene Amino Acid Derivatives. Intra and Inter-molecular Hydrogen Bonded Organization in Solution and Solid State. L. Frkanec, A. Višnjevac, B. Kojić-Prodić, and M. Žinić, Chem. Eur. J., 6, 442-453, 2000. 42. meso-N,N’-Oxalyldivaline. B. Perić, B. Kojić-Prodić, J. Makarević, M. Jokić, and M. Žinić, Acta Cryst. C57, 747-748, 2001. 43. A New 4,9-Diazapyrenium Intercalator for Single and Double Stranded Nucleic Acids: Distinct Differences to Related Diazapyrenium Compounds and Ethidium Bromide. I. Piantanida, B.S. Palm, M. Žinić, and H.-J. Schneider, J. Chem. Soc., Perkin Trans. 2, 1808-1816, 2001. 44. Synthesis, NMR and MS Study of Novel N-Sulfonylated Purine Derivatives. B. Žinić, I. Krizmanić, D. Vikić-Topić, D. Srzić, and M. Žinić, Croat. Chem. Acta, 74, 399-414, 2001. 45. Phenanthridinium Cyclobisintercalands. Fluorescence Sensing of AMP and Selective Binding to Single-Stranded Nucleic Acids. I. Piantanida, B. S. Palm, P.Čudić, M. Žinić, and H.-J. Schneider, Tetrahedron Lett.,42, 6779-6783, 2001. 46. Bis(Amino Acid) Oxalyl Amides as Ambidextrous Gelators of Water and Organic Solvents: Supramolecular gels With Temperature Dependent Assembly/Dissolution Equilibrium. J. Makarević, M. Jokić, B. Perić, V. Tomišić, B. Kojić-Prodić, and M. Žinić, Chem. Eur. J., 7, 3327-3341, 2001. 47. Intermolecular Contacts in the Crystal Packing of 2,2-(N,NOxalyldiimino)-bis(3-phenylpropanamide)dimethyl Sulfoxide Solvate. B. Perić, J. Makarević, M. Jokić, B. Kojić-Prodić, and M. Žinić, Acta Cryst. C57, 865-867, 2001. 48. Benziamidine. M. Jokić, M. Bajić, M. Žinić, B. Perić, and B. Kojić-Prodić, Acta Cryst. C57, 2001,1354-1355. 49. Interactions of novel phenanthridinium-nucleobase conjugates with complementary and non- complementary nucleotides in aqueous media. Tumir, L.-M.; Piantanida, I.; Novak, P.; Žinić, M., J. Phys. Org. Chem. (2002), 15, 599-607. 50. Structural and Chiroptical Properties of Acyclic and Macrocyclic 1,5Bis(oxazoline) Ligands and Their Copper(I) and Silver(I) complexes Hollosi, M.; Majer, Z.; Vass, Elemer, Raza, Z.; Tomišić, V.; Portada, T.; Piantanida, I.;Žinić, M.; Šunjić, V.. Eur. J. Inorg. Chem. (2002), 1738-1748. 51. Interactions of phenanthridinium conjugates with polynucleotides in aqueous media. Recognition of poly U Juranović, I.; Meić, Z.; Piantanida, I.; Tumir, M.; Žinić, M. J. Chem. Soc. Chem. Commun. (2002), 1432-1433. 52. Gels with exceptional thermal stability formed by bis(amino acid) oxalamide gelators and solvents of low polarity. Makarević, J.; Jokić, M.; Frkanec, L.; Katalenić, D.; Žinić, M., J. Chem. Soc. Chem. Commun. (2002)-2238-2239. 53. Lipophilic derivative of rhodamine 19: characterization and spectroscopic properties S. Miljanić, Z. Cimerman, L. Frkanec, M. Žinić Analytica Chimica Acta, (2002), 468, 13-25. 54. New Porphyrin-Nucleobase Hybrid Compounds and Their Interaction with Nucleosides And Nucleic Acids V. Malinovski, L. Tumir, I. Piantanida, M. Žinić, H.-J. Schneider Eur. J. Org. Chem. (2002), 3785-3795. 55. Bis(PheOH) Maleic Acid Amide-Fumaric Acid Amide Photoizomerization Induces Microsphere to Gel Fiber Morphological Transition. The Photo-induced Gelation System. Frkanec, L.; Jokić, M.; Makarević, J.; Wolfsperger, K.; Žinić, M., J. Am. Chem. Soc. (2002), 124, 9716-9717. 56. Macrocyclic vs. acyclic derivatives of chiral bis(oxazolines); ligand distortion and enantioselectivity of Pd(II) complexes in catalytic allylic alkylation D. Šepac, Ž. Marinić, T. Portada, M. Žinić, V. Šunjić Tetrahedron, 2002, accepted. 57. Supramolecular aggregation using synthons with NHCO(S)CS-NH and NHCOCONH functionalities: crystal structures of (S,S)-N,N’monothio- oxalayldileucine methyl ester and its dithio analogue B. Perić, B. Kojić-Prodić, J. Makarević, M. Jokić, M. Žinić Acta Cryst. B, 2002, accepted.