An investigation of mononuclear and binuclear palladium(II) complexes of egta (egta = glycine,N,N′-(1,2-ethanediylbis(oxy-2,1-ethanediyl)bis[N-carboxymethyl]) by 1H-, 13C- and 15N-n.m.r. methods

1:1 and 2:1 palladium(II) complexes of egta^4– (egta^4– = glycine, N,N-(1,2-ethanediylbis)(oxy-2,1-ethanediyl)bis[N-carboxymethyl]) were prepared by 1:1 and 2:1 addition of K₂PdCl₄ to K₄egta, and examined by ¹H-, ¹³C- and ¹⁵N-n.m.r. methods. The 1:1 complex, [Pd(egta)]^2– in solution, utilizes a square-planar coordination comprised of two nitrogen and two glycinato carboxylate donors of egta^4–, leaving two glycinato carboxylates pendant. The complex has a cis-(R,S) stereochemistry which places both pendant carboxylates below the PdN₂O₂ square plane and the tether backbone of egta^4– in the up, up sense above the same plane. The cis-(R,S) assignment was assisted by computer simulations of the ¹³C-n.m.r. spectrum for four possible isomers. Only cis-(R,S) and trans-(R,R) calculated ¹³C-spectra were compatible with the observed ¹³C-n.m.r. pattern. The HH NOESY spectrum of [Pd(egta)]^2– detects long range coupling of the backbone –OCH₂CH₂O– linkage with both coordinated and pendant glycinato CH₂ moieties. The cis-(R,S) isomer's tortional movements allow such contacts whereas a trans-(R,R) isomer does not. The 2:1 complex, [Pd₂(egta)(H₂O)₂] in solution has an extended-chain structure with each palladium(II) center coordinated in the mer-iminodiacetate-like coordination with two bound glycinato-functionalities.     

Synthesis and antitumor evaluation of some 1,3-disubstituted tetrahydropyrimido[4,5-c]isoquinolines

Cyclocondensation of 6-amino-2,4-dioxopyrimidine or 2,4,6-triaminopyrimidine with 1-cyclohexenecarbox-aldehyde 13 afforded regiospecifically, tricyclic, angular 1,3-disubstituted tetrahydropyrimido[4,5-c]isoquin-olines 5 and 6 respectively. In addition, 2,4,6-triaminopyrimidine when condensed with 2-chloro-1-cyclohex-enecarboxaldehyde 14 , regiospecifically afforded the angular isomer 6 . However, the cyclocondensation of 2,6-diamino-4-oxopyrimidine with 13 was regioselective and afforded a mixture of the linear and angular tetrahydropyrimidoisoquinolines 2 and 4 . The growth of leukemia L-1210 cells in culture were inhibited 50% by 6 at 9 × 10^?8 M. Compounds 4 and 5 were not significantly active.     

Synthesis of some 2,4-disubstituted tetrahydropyrimido[4,5-b]quinolines as potential antitumor agents

Cyclocondensations of two 2,4-disubstituted 6-aminopyrimidines with 2-chloro-1-cyclohexenecarboxaldehyde afforded in each case a new regiospecific synthesis of tricyclic, linear disubstituted 6,7,8,9-tetrahydro-pyrimido[4,5-b]quinolines 2 and 3 in excellent yields. The linear structures and hence the regiospecificity of the synthesis were established using ¹H nmr and ¹³C nmr. The growth of leukemia L1210 cells in culture was inhibited 50% by 2 at 30 × 10^?6M and 48% by 3 at 100 × 10^?6M.     

A temperature-dependent dynamic rearrangement of cis-(R,S)-[Pd(egta)]2– (egta4–=glycine,N,N′-(1,2-ethanediylbis(oxy-2,1-ethanediyl)bis[N-carboxymethyl]) in aqueous solution

The cis-(R,S)-[Pd(egta)]2– complex, egta4–=glycine, N,N-(1,2-ethanediylbis(oxy-2,1-ethanediyl)bis[N-carboxymethyl]), has been examined by 1H- and 13C-n.m.r. methods over the 18.0 to 95.0°C range in D2O. A dynamic process occurs above 65°C which makes the protons on the NCH2 functionalities of the egta tether become 1H-n.m.r. equivalent. The two states that interconvert coalesce at 81°C. Evidence from 13C-n.m.r. spectra obtained at 81°C show that the in-plane coordinated carboxylates are not lost, but rather a pendant carboxylate becomes attached with loss of the central imino donor. The resultant palladium(II)NO3 intermediate is able to reform cis-(R,S)-[Pd(egta)]2– or, presumably, give trans-(R,R)-[Pd(egta)]2–. The rate limiting step occurs with a rate constant of 178s–1 at 81°C and an activation energy of 20.5kJ/mol. However, competitive aquation of glycinato donors above 85°C prevents isolation of a stable trans-(R,R)-[Pd(egta)]2– isomer.     

Synthesis of a pyrrolo annulated pyrido[2,3-D]pyrimidine as a potential nonclassical antifolate

Cyclocondensation of 2,4,6-triaminopyrimidine ( 4 ) with ethyl N-benzyl-4-oxo-3-pyrrolidine carboxylate ( 5 ) in diphenyl ether regiospecifically afforded a new tricyclic, angular 1,3,8-trisubstituted pyrrolo[3′,4′:4,5]-pyrido[2,3-d]pyrimidine-6-one 1 in excellent yield. The ketoester 5 was prepared by a literature method. Compound 1 in addition to being a new heterocyclic system is an important key precursor to a variety of classical and nonclassical tricyclic, 5-deaza analogues of the folate cofactor 5,10-methylenetetrahydrofolate 3 .