Revue Roumaine de Chimie, 2008, 53(3), 183–187 NEW 1,10-PHENANTHROLINE DERIVATIVES WITH POTENTIAL ANTITUMORAL ACTIVITY ** Florea DUMITRAŞCU, a* Mino R. CAIRA, b Constantin DRĂGHICI, a Miron T. CĂPROIU, a Loredana BARBU a and Barbu MIU c a Centre of Organic Chemistry “C. D. Nenitzescu”, Roumanian Academy, Spl. Independentei 202B, Bucharest 060023, Roumania b Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa c National College "I. C. Bratianu", Armand Calinescu 14, Piteşti, Roumania Received July 30, 2007 The 1,3-dipolar cycloaddition reaction of 1-(4-cyanophenacyl)-1,10-phenanthrolinium ylide 4, with symmetrical and non-symmetrical alkynes gave new pyrrolo[1,2-a][1,10]phenanthrolines 7a-e. The N-(4-cyanophenacyl)-1,10- phenanthrolinium bromide 3, the intermediate for N-ylide 4, was found to possess antitumoral activity. INTRODUCTION ∗ 1,10-Phenanthroline and its derivatives possess a variety of uses, especially as biologically active compounds and chelating agents. 1-6 Among these compounds the quaternary salts of 1,10- phenanthroline have been evaluated as herbicides, carcinostatics and bacteriostatics, as enzyme inhibitors or activators, or as precursors in the field of organic chemistry. 1-16 Recently, N-phenacyl- 1,10-phenanthrolinium bromides were prepared and their chemical, physicochemical and biological properties were investigated. 6-16 Thus, these 1,10- phenanthroline bromides were used for the synthesis of pyrrolo[1,2-a][1,10]phenanthroline derivatives 10-13 which were found to possess biological activity. 6 The stereostructure and crystal structure of thin organic films of the pyrrolo[1,2- a][1,10]phenanthroline derivatives were determined by X-ray analysis. 14-16 Herein we report the synthesis of new pyrrolo[1,2,a][1,10]phenanthroline derivatives 7 obtained by reactions of 1-(4-cyanophenacyl)- 1,10-phenanthrolinium N-ylide 4 with symmetrical and non-symmetrical acetylenic dipolarophiles. The structural assignment of a dihydro- pyrrolophenanthroline derivative 6a as an intermediate in 1,3-dipolar cycloaddition between ∗ Corresponding author: fdumitra@yahoo.com ** Dedicated to the memory of Dr. Dan Răileanu N-ylide 4 and dimethyl acetylenedicarboxylate (DMAD) is also presented. RESULTS AND DISCUSSION The synthesis of pyrrolo[1,2-a] [1,10]phenanthrolines 7 used, as key intermediate, the cycloimmonium bromide 3 which was prepared by N-alkylation of 1,10-phenanthroline 1 with 2-bromo-4'-cyanoacetophenone 2 in acetone under reflux. The structure of bromide 3 was assigned by elemental analysis and NMR spectroscopy. In the 1 H-NMR recorded in DMSO-d 6 the signal for the methylenic protons appear as a sharp singlet with δ = 7.25-7.35 ppm. The broad singlet in 3 resembles the AB system near coalescence. The magnetic non-equivalence of the methylenic protons was explained on the basis of the non- coplanarity of the pyridine and pyridinium rings. This hypothesis was confirmed by X-ray analysis. 8,9 Preliminary investigations indicated that the 1,10-phenanthrolinium bromide 3 presents significant antimicrobial and antitumoral activity. The pyrrolo[1,2-a][1,10]phenanthroline derivatives 7a-e were obtained by 1,3-dipolar cycloaddition reactions between 1-(4-cyanophenacyl)-1,10- phenanthrolinium N-ylide 4 with electron-deficient esters of acetylenedicarboxylic acid and propiolic