Lily J. Ackerman

Structural and spectral studies of copper(II) and nickel(II) complexes of pyruvaldehyde mixed bis{N(4)-substituted thiosemicarbazones}

Abstract Pyruvaldehyde mixed bis(thiosemicarbazones) have been prepared in which the two thiosemicarbazone moieties have different N(4)-substituents. The mixed bis(thiosemicarbazones) and their copper(II) and nickel(II) complexes have been characterized with IR, electronic, mass, 1H NMR (Ni) and EPR (Cu) spectra. Representative crystal structures have been solved of nickel(II) complexes with either a pyruvaldehyde mixed bis(thiosemicarbazone) or a bis(thiosemicarbazone) with identical N(4)-substituents acting as a tetradentate ligand. [Ni(Pu4M4DE)] has an N(4)-methylthiosemicarbazone substituent on the keto “arm” and N(4)-diethylthiosemicarbazone substituent on the aldehyde arm. [Ni(Pu4M)] contains two N(4)-methylthiosemicarbazone moieties. Both bis(thiosemicarbazones) form square-planar N2S2 complexes with nickel(II) and copper(II).

STRUCTURAL AND SPECTRAL STUDIES OF 1-PHENYLGLYOXAL BIS(3-PIPERIDYLTHIOSEMICARBAZONE) AND ITS ZINC(II), CADMIUM(II) AND PLATINUM(II) COMPLEXES

Abstract Zinc(II) and platinum(II) complexes of 1-phenylglyoxal bis(3-piperidylthiosemicarbazone), H2Pgpip, have been prepared and the crystal structures of H2Pgpip and the two metal complexes have been solved. The two arms of H2Pgpip are on the same side of the carbon–carbon backbone and the N(2)H of the phenyl arm hydrogen bonds to the azomethine nitrogen of the aldehyde arm. Loss of the N(2)H hydrogens from both thiosemicarbazone moieties occurs for [Pt(Pgpip)], resulting in coordination of the dianion Pgpip as a tetradentate N2S2 ligand with the expected 5–5–5-chelate ring system. However, [Zn(HPgpip)Cl] involves the monoanion HPgpip on loss of the phenyl arms N(2)H, resulting in a five-coordinate complex with coordination of the two azomethine nitrogens, a thione sulfur (aldehyde arm), a thiolato sulfur (phenyl arm) and an axial chloro ligand in an approximately square pyramidal arrangement.

STRUCTURAL AND SPECTRAL STUDIES OF N-(2-PYRIDYL)-N'-TOLYLTHIOUREAS

Abstract N-(2-pyridyl)-N′- o -tolylthiourea, monoclinic, P2 1 /c, a =5.127(1), b =19.854(2), c=12.077(2) A , β =94.96(1)°, V=1224.7(2) A 3 , Z =4, μ=2.177 mm −1 , N-(2-pyridyl)-N′-m-tolylthiourea, triclinic, P−1, a =9.811(2), b =9.887(4), c=13.595(3) A , α =74.91(3), β =83.58(2), γ =76.27(2)°, V=1235.(7) A , Z =4, m=2.469 mm −1 and N-(2-pyridyl)-N′-p-tolylthiourea, triclinic,P−1, a =9.935(2), b =11.488(2), c=12.569(2) A , α =63.91(2), β =88.60(2), γ =75.04(2)°, V=1238.1(2) A 3 , Z =4, μ=2.154 mm −1 all have an intramolecular hydrogen bond between N′H and the pyridyl nitrogen, as well as intermolecular hydrogen bonding between NH and a thione sulfur of a second molecule to form centrosymmetric dimers. Solution 1 H NMR studies (CDCI 3 ) show the N′H resonance considerably downfield for each thiourea and its position, as well as that of NH, are affected by substituents on the phenyl ring.

Structural and spectral studies of N-2-(4,6-lutidyl)-N′-tolylthioureas

Abstract N -2-(4,6-lutidyl)- N ′- o -tolylthiourea, 4,6LuTuoT, triclinic, P-1 , a =7.470(2), b =9.799(5), c=10.269(3) A , α =90.514(4), β =98.89(3), γ =90.14(3)°, V=742.5(9) A 3 , Z =2, μ=2.09 mm −1 ; N -2-(4,6-lutidyl)- N ′- m -tolylthiourea, 4,6LuTumT, monoclinic, P2 1 /a , a =7.2393(2), b =16.636(3), c=12.557(1) A , β =101.968(9)°, V=1479.4(6) A 3 , Z =4, μ=2.10 mm −1 and N -2-(4,6-lutidyl)- N ′- p -tolylthiourea, 4,6LuTupT, triclinic, P-1 , a =7.883(2), b =7.9024(8), c=23.273(4) A , α =86.49(1), β =86.48(2), γ =88.45(2)°, V=1443.9(7) A 3 , Z =4, μ=2.15 mm −1 . These molecules have an intramolecular hydrogen bond between N′H and the pyridyl nitrogen, as well as intermolecular hydrogen bonding between NH and a thione sulfur of a second molecule to form centrosymmetric dimers. Solution 1 H NMR studies (CDCl 3 ) show the N′H resonance considerably downfield for each thiourea and its position, as well as that of NH, are affected by substituents on the phenyl ring.

The cytotoxicity of symmetrical and unsymmetrical bis(thiosemicarbazones) and their metal complexes in murine and human tumor cells.

A number of thiosemicarbazones have been tested previously and herein are included three bis(thiosemicarbazones) for comparison to the previous derivatives. In general the uncomplexed thiosemicarbazones were more potent in the cytotoxic screens than the bis(thiosemicarbazone) except in the murine L1210 and the human colon SW480 screens. Mode of action studies have only demonstrated slight differences in the effects of the two types of compounds on nucleic acid metabolism. The symmetrical and unsymmetrical bis(thiosemicarbazones) complexes of copper, nickel, zinc, and cadmium have been examined to compare them to the heterocyclic N(4)‐substituted thiosemicarbazones metal complexes. These new derivatives demonstrated excellent activity against the growth of suspended lymphomas and leukemias although it should be pointed out that generally they were not as active as the copper complexes of N(4)‐substituted thiosemicarbazones. Nevertheless, selected bis(thiosemicarbazones) complexes were active against the growth of human lung MB9812, KB nasopharynx, epidermoid A431, glioma UM‐86, colon SW480, ovary 1‐A9, breast MCK‐7, and osteosarcoma Saos‐2. In human HL‐60 promyelocytic leukemia cells the complexes preferentially inhibited DNA and purine syntheses over 60 min. The regulatory enzyme of the de novo purine pathway, IMP dehydrogenase, appeared to be a major target of the complexes. However, minor inhibition of the activities of DNA polymerase α, PRPP‐amido transferase, ribonucleotide reductase, and nucleoside kinases occurred over the same time period. No doubt these effects of the complexes on nucleic acid metabolism were additive since the d[NTP] pool levels were reduced after 60 min as was DNA synthesis. The symmetrical and unsymmetrical bis(thiosemicarbazones) and their metal complexes did not cause as severe DNA fragmentation as the heterocyclic N(4)‐substituted thiosemicarbazone metal complexes; furthermore, their metabolic effects in the tumor cell were more focused on a single synthetic pathway.

Palladium(II) and platinum(II) complexes of 6-methyl-2-acetylpyridine 3-hexamethyleneiminylthiosemicarbazones: A structural and spectral study

Abstract The reaction of 6-methyl-2-acetylpyridine 3-hexamethyleneiminyl-thiosemicarbazone, H6MAchexim, with potassium tetrachloropalladate(II) and tetrachloroplantinate(II) in methanol afforded the complexes [Pd(6MAchexim)Cl] and [Pt(6MAchexim)Cl], respectively. The X-ray crystal structure determination of both shows that anions of H6MAchexim coordinate in a planar conformation to the central palladium(II) or platinum(II) via the pyridyl nitrogen, azomethine nitrogen and thiolato sulfur atoms. The complexes have also been characterized by spectroscopic techniques (IR, UV–VIS and 1H NMR).

Structural and spectral studies of N-(2-pyridyl)-N′-(4-substituted phenyl)thioureas

Abstract The following molecules were found to have intramolecular hydrogen bonding between the N′H and the pyridine nitrogen and intermolecular hydrogen bonding between the NH and a thione sulfur of a second molecule to form dimers: N-(2-pyridyl)-N′-(4-methoxyphenyl)thiourea, PyTu4OMe, triclinic, P-1, a=7.158(4), b=8.742(3), c=10.833(4) A , α=70.53(3), β=74.38(3), γ=73.97(4)°, V=635.5(5) A 3 and Z=2; N-(2-pyridyl)-N′-(4-nitrophenyl)thiourea, PyTu4NO2, monoclinic, P21/c, a=11.670(1), b=5.9225(9), c=18.792(4) A , β=107.99(1)°, V=1244.8(7) A 3 and Z=4; N-(2-pyridyl)-N′-(4-chlorophenyl)thiourea, PyTu4Cl, triclinic, P-1, a=9.939(3), b=11.399(4), c=12.264(5) A , α=65.50(4), β=87.46(3), γ=76.63(3)°, V=1228.1(7) A 3 and Z=4 and N-(2-pyridyl)-N′-(4-bromophenyl)thiourea, PyTu4Br, triclinic, P-1, a=10.020(2), b=11.444(2), c=12.353(5) A , α=64.76(2), β=87.61(3), γ=77.88(2)°, V=1250.8(7) A 3 and Z=4. The methoxy and nitro moieties of PyTu4OMe and PyTu4NO2 also interact with N′H, and there is a weak intermolecular interaction between one of the pyridine hydrogen atoms and the thione sulfur in PyTu4Br. Solution 1H NMR spectral studies (DMSO-d6) show the N′H resonance considerably downfield for each thiourea and its chemical shift, as well as that of NH, is affected by substituents on the phenyl ring.

Structural and spectral characterization of two bis{N(4)-alkylthiosemicarbazones} of 1-phenylglyoxal

Abstract The 1-phenylglyoxal bis{N(4)-methyl- and {N(4)-ethylthiosemicarbazones}, H 2 Pg4M and H 2 Pg4E, have been prepared, studied spectroscopically ( 1 H NMR, ultraviolet and infrared) and their crystal structures solved. Intramolecular hydrogen bonding connects the two thiosemicarbazone moieties in both H 2 Pg4M and H 2 Pg4E such that they are on the same side of the carbon–carbon backbone, and N(4) H hydrogen bonds to the azomethine nitrogen for each moiety.

Structural, spectral and thermal studies of N-2-(picolyl)-N′-4-chlorophenylthioureas

Abstract N -2-(4-picolyl)- N ′-4-chlorophenylthiourea, 4PicTu4ClPh, triclinic, P -1, a =7.5235(3), b =9.1585(5), c=10.5158(7) A , α =76.015(3), β =70.015(4), γ =82.010(4)°, V=1309.8(2) A 3 and Z =2; N -2-(5-picolyl)- N ′-4-chlorophenylthiourea, 5PicTu4ClPh, monoclinic, P 2 1 / c , a =15.139(2), b =4.8386(3), c=17.338(2) A , β =90.661(4)°, V=1270.0(2) A 3 and Z =4 and N -2-(6-picolyl)- N ′-4-chlorophenylthiourea, 6PicTu4ClPh, monoclinic, C 2/ c , a =33.520(6), b =4.0750(3), c=18.658(4) A , β =97.500(6)°, V=2526.8(7) A 3 and Z =8. The most striking difference between the structures of the three thioureas is the difference in planarity, and among the four N -2-(picolyl)- N ′-4-chlorophenylthioureas, their values for Δ H fus .

Structural, spectral and thermal studies of N-2-(4-picolyl)- and N-2-(6-picolyl)-N′-(2-chlorophenyl)thioureas and N-2-(6-picolyl)-N′-(2-bromophenyl)thiourea

Abstract N -2-(4-picolyl)- N ′-2-chlorophenylthiourea, 4PicTu2Cl, monoclinic, P 2 1 / c , a =10.068(5), b =11.715(2), c=11.185(6) A , β =96.88(4)°, V=1309.8(2) A 3 and Z =4; N -2-(6-picolyl)- N ′-2-chlorophenylthiourea, 6PicTu2Cl, triclinic, P -1, a =7.4250(8), b =7.5690(16), c=12.664(3) A , α =105.706(17), β =103.181(13), γ =90.063(13)°, V=665.6(2) A 3 and Z =2 and N -2-(6-picolyl)- N ′-2-bromophenylthiourea, 6PicTu2Br, triclinic, P -1, a =7.512(4), b =7.535(6), c=12.575(4) A , a =103.14(3), β =105.67(3), γ =90.28(4)°, V=665.7(2) A 3 and Z =2. The intramolecular hydrogen bonding between N′H and the pyridine nitrogen and intermolecular hydrogen bonding involving the thione sulfur and the NH hydrogen, as well as the planarity of the molecules, are affected by the position of the methyl substituent on the pyridine ring. The enthalpies of fusion and melting points of these thioureas are also affected. 1 H NMR studies in CDCl 3 show the NH′ hydrogen resonance considerably downfield from other resonances in their spectra.