{"id":247,"date":"2016-12-12T11:35:25","date_gmt":"2016-12-12T09:35:25","guid":{"rendered":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/?page_id=247"},"modified":"2016-12-13T09:10:11","modified_gmt":"2016-12-13T07:10:11","slug":"final-report","status":"publish","type":"page","link":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/final-report\/","title":{"rendered":"5th Stage Report"},"content":{"rendered":"

Raport stiintific <\/em><\/strong>
\nprivind implementarea proiectului<\/em>
\nNoi derivati polifunctionali cu azot (heterocicli, podanzi si macrocicli) ca si elemente cheie inteligente pentru utilizari multiple<\/strong>
\nin perioada ianuarie 2016- decembrie 2016<\/strong><\/em>
\nValorificarea rezultatelor:<\/strong><\/p>\n

\n
Lucrari stiintifice publicate in anul 2016: 4<\/strong><\/li>\n<\/ul>\n
\n
\n
Mantu, D.; Antoci, V.; Moldoveanu, C.; Zbancioc, Ghe.; Mangalagiu, I.I. Hybrid imidazole (benzimidazole) \/ pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity, J. Enzym. Inh. Med. Ch., 31, 1-8, 2016. Publisher: Taylor & Francis, Informa Ltd, ISSN: 1475-6366 (print), 1475-6374 (electronic)\u00a0http:\/\/dx.doi.org\/10.1080\/14756366.2016.1190711<\/a><\/li>\n
Zbancioc, Ghe.; Moldoveanu, C.; Humelnicu, I.; Vasilache, V.; Mangalagiu, I.I. Pyridine \/ Quinoline Derivatives Bearing a Imidazole \/ Benzimidazole Moiety: a LC-MS Approach of Structure Determination, Rev. Chim.-Bucharest, 67(8), 1516-1519, 2016. Publisher: SYSCOM 18 SRL, CODEN: RCBUAU ISSN: 0034-7752.\u00a0 ROMANIA<\/li>\n
Antoci, V.; Humelnicu, I.; Vasilache, V.; Mantu, D. Synthesis, Structure and Biological Activity of Some Hybrid Benzimidazole \/ Quinoline Derivatives, Rev. Chim.-Bucharest, 67(9), 1713-1716, 2016. Publisher: SYSCOM 18 SRL, CODEN: RCBUAU ISSN: 0034-7752.\u00a0 ROMANIA<\/li>\n
Mangalagiu, I.I. Vasilache, V. New podants with azaheterocycles skeleton as smart versatile building blocks for multiple tasks, Chemical Sciences Journal (Conference Series) 7:2 (suppl.), pag. 27, 2016. ISSN: 2150-3494. http:\/\/dx.doi.org\/10.4172\/2150-3494.C1.002<\/a><\/li>\n<\/ol>\n<\/ol>\n
\n
Lucrari prezentate la congrese: 13 (3 conferinte invitate, o prezentare orala, 9 postere)<\/strong><\/li>\n<\/ul>\n\n
\n
Mangalagiu, I.I. Vasilache, V. New podants with azaheterocycles skeleton as smart versatile building blocks for multiple tasks, European Chemistry Congres, June 16-18, 2016, Rome, Italy. pag.27 (plenary lecture). http:\/\/chemistry.conferenceseries.com\/europe\/2016<\/a><\/li>\n
Mangalagiu, I.I., Nitrogen heterocycles derivatives: new achievements, XXXIV-th ROMANIAN CHEMISTRY CONFERENCE, 4-7 October 2016, Calimanesti-Caciulata, Romania, C.P.-8, pag.5. (Plenary Lecture). http:\/\/conferinta.oltchim.ro\/<\/a><\/li>\n
Mangalagiu, I.I. New azaheterocycles derivatives of potential interest in leishmaniasis, 3rd COST Action CM1307 Conference \/ SOCEPA \/ SEFIG Joint Meeting \u201cAntiparasitic Chemotherapy for Human and Veterinary Use\u201d, October 24-26, 2016, Madrid, Spain. P.L-3, pag.21 (Plenary Lecture).http:\/\/www.costcm1307.org\/CM1307\/Abstract_3rd_COST_Action_CM1307_Conference_SOCEPA_SEFIG.pdf<\/a><\/li>\n
Mangalagiu, I.I. Vasilache, V. New podants with azaheterocycles skeleton as smart versatile building blocks for multiple tasks, 6-th EuCheMS Chemistry Congres, September 11-15, 2016, Seville, Spain. OP 1386 (Oral Presentation). euchems-seville2016.eu<\/a><\/li>\n
Vasilache, V.; Mantu, D.; Antoci, V.; Mangalagiu, I.I. New bis-pyridazine derivatives of potential interest in leishmaniasis, 3rd COST Action CM1307 Conference \/ SOCEPA \/ SEFIG Joint Meeting \u201cAntiparasitic Chemotherapy for Human and Veterinary Use\u201d, October 24-26, 2016, Madrid, Spain. P.-2, pag.88 (Poster).http:\/\/www.costcm1307.org\/CM1307\/Abstract_3rd_COST_Action_CM1307_Conference_SOCEPA_SEFIG.pdf<\/a><\/li>\n
Antoci, V.; Mantu, D.; Vasilache, V.; Bratanovici, I.B.; Mangalagiu, I.I. Highly sensitive chemosensors for Zn2+ and its coordination complexes based on podants with azaheterocycles skeleton, European Exhibition of Creativity and Invovation, Euroinvent 2016, May 19-21 2016, Iasi, Romania. Class: Inovative Research, pag. 302. RO-41. Poster, ISBN 978-606-775-212-0. http:\/\/eudirect.ro\/euroinvent\/<\/a><\/li>\n
Zbancioc, Ghe.; Moldoveanu, C.; Grigore, M.M.; Mangalagiu, I.I. Hybrid imidazole \/ pyridine (quinoline) derivatives with anticancer and antimycobacterial activity, European Exhibition of Creativity and Invovation, Euroinvent 2016, May 19-21 2016, Iasi, Romania. Class: Inovative Research, pag. 302. RO-40. Poster, ISBN 978-606-775-212-0. http:\/\/eudirect.ro\/euroinvent\/<\/li>\n
Bratanovici, B.; Amariucai-Mantu, D.; Antoci,V.;Ciobanu, C.-I.; Moldoveanu, C.; Mangalagiu, I.I.: New bis-pyridine-imidazolium\/benzimidazoliumsalts with acetophenone skeleton: synthesis and NMR characterization, \u201cAlexandru Ioan Cuza\u201d University Days, Faculty of Chemistry Conference, 27-29 October 2016, Ia\u015fi, Rom\u00e2nia. P17, pag. 40.<\/li>\n
Grigore,M.-M.; Antoci,V.; Amariucai-Mantu, D.; Ciobanu, C.-I.; Zbancioc, Ghe.; Mangalagiu, I.I.: Synthesisand NMRcharacterization of novel anthracene-imidazolium\/benzimidazolium salts, \u201cAlexandru Ioan Cuza\u201d University Days, Faculty of Chemistry Conference, 27-29 October 2016, Ia\u015fi, Rom\u00e2nia. P18, pag. 41. (Book of abstracts on CD).<\/li>\n
Amariucai-Mantu, D.; Antoci, V.; Moldoveanu, C.; Bratanovici, B.; Mangalagiu, I.I. NEW BIS-PYRIDINE-IMIDAZOLE\/BENZIMIDAZOLE DERIVATIVES: SYNTHESIS AND THEIR BIOLOGICAL PROPERTIES, XXXIV-th ROMANIAN CHEMISTRY CONFERENCE, 4-7 October 2016, Calimanesti-Caciulata, Romania, P.S.I-5, pag.5, (Poster). http:\/\/conferinta.oltchim.ro\/<\/a><\/li>\n
Zbancioc, Ghe.; Moldoveanu, C.; Antoci, V.; Amariucai-Mantu, D.; Mangalagiu, I.I. MICROWAVE ASSISTED SYNTHESIS OF SOME BENZOFURAN DERIVATIVES WITH FLUORESCENT PROPERTIES, XXXIV-th ROMANIAN CHEMISTRY CONFERENCE, 4-7 October 2016, Calimanesti-Caciulata, Romania, P.S.I-10, pag.10, (Poster). http:\/\/conferinta.oltchim.ro\/<\/a><\/li>\n
Antoci, V.; Amariucai-Mantu, D.; Ciobanu, C.; Zbancioc, Ghe.; Grigore, M.M.; Mangalagiu, I.I. NOVEL BIS-ANTHRACENE-IMIDAZOLIUM SALT: UV-VIS, AND NMR STUDIES ON IONS ACETATE COMPLEXATION, XXXIV-th ROMANIAN CHEMISTRY CONFERENCE, 4-7 October 2016, Calimanesti-Caciulata, Romania, P.S.I-30, pag.30, (Poster). http:\/\/conferinta.oltchim.ro\/<\/a><\/li>\n
Mantu, D.; Antoci, V.; Vasilache, V.; Mangalagiu, I.I. Synthesis, structure and biological activity of some azine and azol derivatives, Chimia 2016, May 26-28, 2016. Constanta, Romania. PA3, pag 20. OVIDIUS UNIVERSITY PRESS, CONSTAN\u021aA 2016, ISSN 2360-3941 http:\/\/chimia2016.univ-ovidius.ro\/<\/a><\/li>\n<\/ol>\n<\/ol>\n
\n
Premii 2016: 2<\/strong><\/li>\n<\/ul>\n
\n
\n
Mai 19-21, 2016<\/strong>. \u201cGold Medal\u201d.<\/strong> Lucrare premiata: \u201eHybrid imidazole \/ pyridine (quinoline) derivatives with anticancer and antimycobacterial activity\u201d, Euroinvent 2016<\/strong>, Iasi, Romania;<\/li>\n
Mai 19-21, 2016<\/strong>. \u201cSilver Medal\u201d.<\/strong> Lucrare premiata: \u201e Highly sensitive chemosensors for Zn2+ and its coordination complexes based on podants with azaheterocycles skeleton\u201d, Euroinvent 2016<\/strong>, Iasi, Romania;<\/li>\n<\/ol>\n<\/ol>\n\n
2016 Etapa V. Sinteza si analiza structurala a\u00a0 macrociclurilor si podantilor<\/strong><\/li>\n<\/ul>\n
A.V.1.\u00a0 Sinteza intermediarilor necesari (asa cum s-a descris la I.1 si I.2)<\/strong><\/p>\n
In vederea realizarii acestui obiectiv s-a avut in vedere obtinerea unor intermediari azaheterociclici \u201ctinta\u201d, care sa poata fi utilizati ulterior in scopul dorit. S-a dorit ca sintezele sa fie cat mai directe, economice si eficiente. Astfel:<\/p>\n
a. S-au obtinut intermederi din categoria azaheterociclicurilor saraci in electroni de 6 atomi, si anume piridine halogenate cu reactivitate marita (prin reactia de halogenare directa a alcoolului):<\/p>\n
$\"\"$ <\/a><\/p>\n
b. S-au obtinut intermediari din categoria azaheterociclicurilor bogati in electroni de 5 atomi, atit din categoria imidazolului si benzimidazolului. Si in acest caz s-au utilizat cai directe si eficiente de reactie:
\n– benzimidazolul a fost sintetizat din diamina corspunzatoare si apoi N-alchilat prin aditie Michael; aceiasi aditie Michael a fost folosita si in cazul imidazolului:<\/p>\n
$\"\"$ <\/a><\/p>\n
c. Derivatii acetofenonici bromurati au fost obtinuti prin reactia de bromurare in cataliza heterogena a dihidroxiacetofenonelor:<\/p>\n
$\"\"$ <\/a><\/p>\n
A.V.2. Sinteza de macrocicli de tip P7 continind in aceiasi molecula azaheterocicli saraci in electroni de 6 atomi si bogati in electroni de 5 atomi, conectati prin diversi spatiatori<\/strong><\/p>\n
Aceasta etapa a avut ca si obiectiv principal sinteza de noi macrocicluri de tip P7<\/strong> continind in aceiasi molecula azaheterocicli saraci in electroni (\u03c0\u2013deficitari) de 6 atomi si bogati in electroni (\u03c0\u2013bogati) de 5 atomi. Cele doua tipuri de heterocicluri sunt conectate intre ele prin diversi spatiatori.
\nPentru sinteza macrociclurilor de tip P7<\/strong> s-au utilizat doua cai de reactie:<\/p>\n
\n
I. O prima cale de sinteza porneste de la dihidroxiacetofenone nesubstituite si consta intr-un proces de \u03b1\u2013bromurare la nivelul metilului acetofenonic (bromurare in cataliza heterogena) conducind la acetofenonele \u03b1\u2013bromurate I<\/strong>, care sunt utilizate in urmatoarea etapa pentru cuaternizarea derivatilor imidazolici, conducind la dihidroxiacetofenonele cu schelet imidazolic tip II<\/strong>; compusii de tip II<\/strong> au fost supusi in continuare unui proces de bis-eterificare cu derivati piridinici contind un halogen activ, proces care conduce la podanzii imidazo-acetofenono-dihidroxipiridinici Pi<\/strong>, care contin la rindul lor alte doua grupari metilen-halogenice reactive; in urmatoarea etapa, podanzii de tip Pi<\/strong> continind doua grupari metilen-halogenice reactive au fost supuse unui proces macrociclizare conducind la macrociclii corespunzatori de tip P7<\/strong>.<\/li>\n<\/ul>\n $\"\"$ <\/a><\/p>\n
\n
II. O a doua cale de sinteza porneste de la dihidroxiacetofenone nesubstituite si consta in bis-eterificare initiala a dihidroxiacetofenonelor cu derivati piridinici contind un halogen activ, care conduce la derivati acetofenono-dihidroxipiridinici continind doua grupari metilen-halogenice reactive; in urmatoarea etapa, derivati acetofenono-dihidroxipiridinici continind doua grupari metilen-halogenice reactive au fost supuse unui proces macrociclizare conducind la macrociclii corespunzatori de tip P7\u2019<\/strong>; ulterior, macrocicli P7\u2019 <\/strong>au fost supusi unui proces de \u03b1\u2013bromurare la nivelul metilului acetofenonic (bromurare in cataliza heterogena) conducind la macrociclii de tip P7\u2019\u2019 <\/strong>\u03b1\u2013bromurati, care in final au fost utilizati pentru cuaternizarea derivatilor imidazolici, generind in final macrociclii corespunzatori de tip P7, <\/strong>continind in aceiasi molecula azaheterocicli saraci in electroni (\u03c0\u2013deficitari) de 6 atomi si bogati in electroni (\u03c0\u2013bogati) de 5 atomi.<\/li>\n<\/ul>\n $\"\"$ <\/a><\/p>\n
Macrociclurilor de tip P7<\/strong> le-au fost testate abilitatile de complexare ca si chemosenzor pentru metale, precum si activitatea biologica antimicrobiana si anticanceroasa (vezi A.V.3).
\nAstfel, macrociclurile de tip P7<\/strong> au fost complexate cu metale bivalente (cupru si zinc) si s-a testat posibilitatea de a functiona ca si poarta logica (logic gate), via fotoinducted electron transfer (PET). Cercetarile au aratat ca intradevar P7<\/strong> functioneaza ca o poarta logica de tip AND, cu doua si\/sau trei inputuri (H^{+<\/sup>\/2H^{+<\/sup> \u00a0si M^{2+<\/sup>) si un output (fluorescenta), sistemul functionind dupa filozofia fluorofore-spacer-receptor-spacer-fluorofore. \u00a0In schema de mai sus este prezentat schema logica si tabelul de adevar.<\/p>\n}}}
$\"\"$ <\/a><\/p>\n
A.V.3. Evaluarea proprietatilor biologice<\/strong><\/p>\n
Lu\u00e2nd \u00een considerare c\u0103 azaheterociclii si dihiroxiacetofenonele posed\u0103 o gam\u0103 vast\u0103 de activitati biologice, o\u00a0 parte din compusii obtinuti au fost testati din punct de vedere al activitatii antimicrobiene si antineoplazice.
\nActivitatea antibacteriana a fost testata pe nou\u0103 specii de bacterii: bacterii gram-positive (Staphylococcus aureus<\/em> ATCC 25923, Sarcina lutea<\/em> ATCC 9341, Bacillus cereus<\/em> ATCC 14579, Bacillus subtilis<\/em>), bacterii gram-negative (Escherichia coli,<\/em> Pseudomonas aeruginosa<\/em> ATCC 27853) \u015fi fungi ( Candida albicans<\/em> ATCC 10231, Candida glabrata<\/em> ATCC MYA 2950 and Candida sake <\/em>).<\/em> Ca si metoda de lucru s-a folosit metoda difuziometrica orizontala pe agar. Rezultatele obtinute au demonstrat ca macrociclurile poseda o activitate semnificativa impotriva unor germeni gram-negativi, rezultat incurajator deoarece nevoia de compusi biologic activi pentru astfel de germeni este foarte mare. Fata de levurile testate compusii nu au fost activi.<\/p>\n
S-a testat activitatea antineoplazica pe celule tip HeLa (human cervical endothelial carcionoma) si HepLa (hepatic carcinoma).\u00a0 S-a constatat ca macrociclurile testate nu au o acivitate antineoplazica promitatoare.<\/p>\n
A.V.4. Analiza structurala si elementala a noilor compusi obtinuti. Raport final de etapa si de grant<\/strong><\/p>\n
Acest lucru s-a efectuat pentru toti compusii obtinuti prin analiza elementala, spectrometrie IR , UV-VIS, fluorescenta, \u00a0H-RMN, C-RMN, experimente bidimensionale de RMN (COSY, HMQC, HMBC), spectrometrie de masa. S-a efectuat raportul fina de etapa si de grant.<\/p>\n","protected":false},"excerpt":{"rendered":"
Raport stiintific privind implementarea proiectului Noi derivati polifunctionali cu azot (heterocicli, podanzi si macrocicli) ca si elemente cheie inteligente pentru utilizari multiple in perioada ianuarie 2016- decembrie 2016 Valorificarea rezultatelor: Lucrari stiintifice publicate in anul 2016: 4 Mantu, D.; Antoci, V.; Moldoveanu, C.; Zbancioc, Ghe.; Mangalagiu, I.I. Hybrid imidazole (benzimidazole) \/ pyridine (quinoline) derivatives and […]<\/p>\n","protected":false},"author":64,"featured_media":0,"parent":0,"menu_order":9,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/wp-json\/wp\/v2\/pages\/247"}],"collection":[{"href":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/wp-json\/wp\/v2\/users\/64"}],"replies":[{"embeddable":true,"href":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/wp-json\/wp\/v2\/comments?post=247"}],"version-history":[{"count":4,"href":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/wp-json\/wp\/v2\/pages\/247\/revisions"}],"predecessor-version":[{"id":260,"href":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/wp-json\/wp\/v2\/pages\/247\/revisions\/260"}],"wp:attachment":[{"href":"http:\/\/teclu.chem.uaic.ro\/chemosensors\/wp-json\/wp\/v2\/media?parent=247"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}