Thomas A. Mayer

Synthesis, crystal structure, and enhancement of the efficacy of metronidazole against Entamoeba histolytica by complexation with palladium(II), platinum(II), or copper(II)

Reaction of trans-[PdCl2(DMSO)(2)]. cis-[PtCl2(DMSO)(2)]. and [Cu(OAc)(2)](H2O)-H-. with metronidazole (mnz) leads to the formation of new complexes, i.e., trans-[PdCl2(mnz)(2)] (1), trans-[PtCl2(mnz)(2)] (2). and trans-[Cu-2(OAc)(4)(mnz)(2)] (3), respectively. Complexes 1-3 crystallize all in the centrosymmetric monoclinic space group P2(1)/c with Z = 8. Unit-cell parameters for these complexes are: 1, a = 7.1328(14) Angstrom, b = 20.699(4) Angstrom, c = 7.1455(14) Angstrom, and beta = 116.17(3)degrees; 2, a = 9.9169(14) Angstrom, b = 21.853(4) Angstrom, c = 6.7218(13) Angstrom, and beta = 110.79(3)degrees: 3. a = 9.1663(18) Angstrom, b = 19.129(4) Angstrom, c = 8.9446(18) Angstrom, and beta = 116.44(3)degrees. The complexes 1 and 2 maintain an ideal square-planar geometry. In complex 3, the H2O molecules of the starting complex are replaced by metronidazole while maintaining a dimeric structure of [Cu(OAc)(2)]. Each Cu ion has an ideal octahedral structure, though distortion occurs in the equatorial position where the acetato ligands are attached. The Cu-Cu separation of 2.6343(8) Angstrom indicates considerable metal-metal interaction. The testing of the antiamoebic activity of these complexes against the protozoan parasite Entamoeba histolytica suggests that compound 1-3 might be endowed with important antiamoebic properties since they showed IC50 values in a muM range better than metronidazole (Table 2). Thus, compound 1 displayed more effective amoebicidal activity than metronidazole (IC50 values of 0.103 muM vs. 1.50 muM resp.).

Structural investigations of phosphorus-nitrogen compounds. 4. Steric and electronic effects in dibenzylamino derivatives of hexachlorocyclotriphosphazatriene and 4,4,6,6-tetrachloro-2,2-diphenylcyclotriphosphazatriene

A systematic study is presented on the products of aminolysis of N(3)P(3)Cl(6) (1) and N(3)P(3)Ph(2)Cl(4) (4) with dibenzylamine. Two series of mono- and disubstituted derivatives of compounds (1) and (4), namely N(3)P(3)Cl(5)[N(CH(2)Ph)(2)] (2) and N(3)P(3)Cl(4)[N(CH(2)Ph)(2)](2) (3) and N(3)P(3)Ph(2)Cl(3)[N(CH(2)Ph)(2)] (5) and N(3)P(3)Ph(2)Cl(2)[N(CH(2)Ph)(2)](2) (6) [where (2), (3), (5) and (6) are new structures], are investigated in order to determine whether steric or electronic effects prevail in the formation of dibenzylamino-substituted cyclophosphazenes. The influence of an electron-releasing group (i.e. phenyl) on the stereochemistry and degree of substitution of the product is analysed by comparison of the above two series. The difference in unsymmetrically substituted endocyclic P-N bond lengths, Delta, is used as a measure of the degree of the electronic contribution, in combination with basicity constants, to quantify the degree of the electron-releasing capacity of the R group. In order to compare geminal versus non-geminal substitution, a difunctional secondary amine was used to form the compound N(3)P(3)Cl(4)[NMe(CH(2))(3)NMe] (7) (a reinvestigation) for inclusion in this study. It is shown that electron-releasing groups have a greater effect on the lengthening of P-Cl bonds as opposed to endocyclic P-N bonds and that this effect is greater in the non-geminal PRCl case than for geminal PCl(2). However, steric effects are shown to be dominant in the reactions of dibenzylamine with N(3)P(3) derivatives, with a disposition to a trans stereochemistry in bisdibenzylamino derivatives.

Structural investigations of phosphorus–nitrogen compounds. 6. Relationships between molecular parameters in per-X-substituted bridged spermine derivatives and basicity constants ΣαR of substituents

A systematic study is reported of the products of the nucleophilic substitution reactions of the spermine-bridged cyclotriphosphazene, [N3P3X4(NHCH2CH2CH2N)CH2CH2]2 [where X = Cl (2a)], to give a number of new structures [(2b)-(2g)] in which X = OPh, [spiro-O(CH2)3O]0.5, Ph, NHPh, NC4H8 and NHBut, respectively. A comparison has been made between the sum of the substituent basicity constants, Sigmaalpha(R), obtained in nitrobenzene solution, and ten molecular parameters of the N3P3 ring (the internal bond angles alpha, beta, gamma, delta and theta;, and the P-N bond lengths a, b, c, d and e) as well as the difference between the bond lengths a and b, Delta(P-N). It is found that the systematic change in molecular parameters of compounds (2a)-(2g) is in line with changes in alphaR values, indicating the similarity in relative electron-releasing capacity of substituents X in the solid state and in solution. It is also found that the effect on molecular parameters of (2a)-(2g) with two X substituents in PX2 groups is greater than that for one X substituent in P(OR)X groups in an analogous series of compounds observed previously [Besli et al. (2002). Acta Cryst. B58, 1067-1073].

Structural investigations of phosphorus–nitrogen compounds. 5. Relationships between molecular parameters of 2,2-diphenyl-4,6-cis-oxytetra­(ethyl­ene­oxy)-4,6-R2-cyclotriphosphazatrienes (R = Cl, OCH2CF3, OPh, OMe, NHPh, NHBut) and substituent basicity constants

A systematic study of the products of nucleophilic substitution reactions of cis-ansa N(3)P(3)Ph(2)[O(CH(2)CH(2)O)(4)]Cl(2) (3) is reported. These reactions give a number of new structures with the general formula N(3)P(3)Ph(2)[O(CH(2)CH(2)O)(4)]R(2) [where R = OCH(2)CF(3) (4), OPh (5), OMe (6), NHPh (7 x H(2)O), NHBu(t) (8)]. A comparison has been made between the sum of the substituent basicity constants, Sigmaalpha(R), that are obtained in nitrobenzene solution and eight molecular parameters of the N(3)P(3) ring [the P-N bond lengths a, b, c; the internal bond angles alpha, beta, gamma, delta; and the difference between the bond lengths a and b, Delta(P-N)]. It is found that the systematic changes in the molecular parameters of (3)-(8) are in line with changes in alpha(R) values. This result implies the similarity in relative electron-releasing capacity of substituents R in the solid state and in solution.

Poly­[[hexaacetatodiethano­ltrimagnesium(II)] diethanol solvate], a polymeric acetate-bridged magnesium chain structure

The title compound, [Mg3(C2H3O2)6(C2H6O)2]·2C2H6O, contains infinite chains of magnesium ions bridged by acetate ligands in three different coordination modes. There are two independent MgII ions in the asymmetric unit, and one lies on a twofold axis. The coordination geometry around each Mg ion is distorted octahedral.

Hydrogen bonding networks and anion coordination in (η6-arene)Cr(CO)3 complexes: metal carbonyls as hydrogen bond acceptors

A chloride selective amide cleft molecule 2 containing two Cr(CO)3 moieties has been synthesised by condensation of (η6-aniline)Cr(CO)3 3 with isophthaloyl dichloride; the X-ray crystal structure of 2 contains a network of Cr–CO···HN hydrogen bonds giving rise to an extended three-dimensional coordination array; the X-ray crystal structure of (η6-aniline)Cr(CO)3 3 has been re-determined and found to contain bifurcated amine NH···OC–Cr hydrogen bonds.

Chiral configurations of spermine-bridged cyclotriphosphazatrienes

Spermine-bridged gem-disubstituted cyclotriphosphazatrienes have been synthesised by two routes. In one route a spermine-bridged cyclophosphazene 2 reacted with monofunctional nucleophiles known to favour gem disubstitution in cyclophosphazene rings (e.g.tert-butylamine) to give 3b, or to favour formation of spiro-derivatives with difunctional nucleophiles (e.g. 1,3-propanediol) to give 3c. In the other route a gem-disubstituted cyclophosphazene (i.e. diphenyl, N3P3Ph2Cl4, compound 4) reacted with spermine to give 3a. The >P(N-spiro) group in each cyclophosphazene ring of 3a–c is stereogenic and homotopic, and so it is expected, and confirmed, that the spermine-bridged gem-disubstituted cyclotriphosphazatrienes (3a–c) should be chiral and exist in meso and racemic forms. The proton-decoupled 31P NMR spectroscopy of 3a–c gave rise to two sets of signals in a 1 ∶ 1 ratio consistent with formation of meso and racemic forms. The meso and racemic forms of 3a (gem-diphenyl derivative) were separated by column chromatography and characterised by X-ray crystallography; this enabled the unequivocal assignment of the two sets of 31P NMR signals to the meso and racemic forms of 3a. This is the first time that the existence of chiral configurational isomers has been elucidated in the field of spermine-bridged cyclophosphazene compounds, and only the second time in cyclophosphazene chemistry.