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One interesting approach to fight tuberculosis is the use of prodrugs that often have shown improved biological activities over drugs with poor absorption or difficulty to cross membranes. Previous studies demonstrate that weak acids such as benzoic acid, present antimycobacterial activity. Moreover, esters of those acids revealed to be a viable alternative since they may diffuse more easily through the cell membranes. Previously we showed that mycobacteria can easily activate benzoic acid esters by conversion to the corresponding acid. Since Zhang postulated that the activity of the acids can be dependent on their pKa, we set up to synthesize a library of benzoates with different electron withdrawing groups (4-chloro, 2,6-dichloro, 3,5-dichloro, 4-nitro, and 3,5 dinitro), to modulate pKa of the liberated acid and different alkoxy substituents (propyl, hexyl, and phenyl) to modulate their lipophilicity, and tested the activity of the esters and the corresponding free acids against mycobacteria. We also studied the activation of the esters by mycobacterial enzymes and the stability of the compounds in buffer and plasma. We concluded that all the benzoates in our study can be activated by mycobacterial enzymes and that the phenyl and hexyl esters presented higher activity than the corresponding free acids, with the nitrobenzoates, and especially the dinitrobenzoates, showing very interesting antitubercular activity that deserve further exploration. Our results did not show a correlation between the activity and the pKa of the acids. [ABSTRACT FROM AUTHOR]

Three new nickel(II)-hmt complexes [Ni(2-nbz) 2 (μ 2 -hmt)(H 2 O) 2 ] n ( 1 ), [Ni(3-nbz) 2 (hmt) 2 (H 2 O) 2 ]·2(3-nbzH) ( 2 ) and [Ni(4-nbz) 2 (μ 2 -hmt)(H 2 O) 2 ] n ( 3 ) bearing isomeric nitrobenzoates [2-nbz = 2-nitrobenzoate, 3-nbz = 3-nitrobenzoate, 4-nbz = 4-nitrobenzoate and hmt = hexamethylenetetramine] have been synthesised by self-assembly and crystallographically characterised. Compounds 1 and 3 are zigzag chain 1D polymers whereas complex 2 is a monomer. Various weak forces, i.e . –NO 2 –π, π–π and CH–π interactions play a key role in stabilizing the structures of 1 , 2 and 3 , which are further extended into the distinct 1D ( 2 ), 2D ( 1 ) or 3D ( 3 ) H-bonded networks via the intermolecular O–H⋯N ( 1 – 3 ) and O–H⋯O ( 3 ) interactions involving the H 2 O ligands and hexamethylenetetramine and/or nitrobenzoate moieties. The H-bonded 2D and 3D networks in 1 and 3 have been topologically classified as trinodal 3,4,6-connected or 3,4,4-connected nets with the 3,4,6L6 or sqc69 topologies, respectively. [ABSTRACT FROM AUTHOR]

Highlights: [•] Self-assembled coordination complexes of Cd(II) with hmt. [•] Very low angle between two hmt moieties in one compound. [•] Noncovalent interactions lead to formation of polymers. [Copyright &y& Elsevier]

Abstract: Three new zinc(II)-hexamethylenetetramine (hmt) complexes [Zn2(4-nbz)4(μ2-hmt)(OH2)(hmt)] (1), [Zn2(2-nbz)4(μ2-hmt)2] n (2) and [Zn3(3-nbz)4(μ2-hmt)(μ2-OH)(μ3-OH)] n (3) with three isomeric nitrobenzoate, [4-nbz=4-nitrobenzoate, 2-nbz=2-nitrobenzoate and 3-nbz=3-nitrobenzoate] have been synthesized and structurally characterized by X-ray crystallography. Their identities have also been established by elemental analysis; IR, NMR, UV–Vis and mass spectral studies. 1 is a dinuclear complex formed by bridging hmt with μ2 coordinating mode. The geometry around the Zn centers in 1 is distorted tetrahedral. Paddle-wheel centrosymmetric Zn2(2-nbz)4 units of complex 2 are interconnected by μ2-hmt forming a one-dimensional chain with square-pyramidal geometries around the Zn centers. Compound 3 contains a μ2/μ3-hydroxido and μ2-hmt bridged 1D chain. In this complex, varied geometries around the Zn centers are observed viz. tetrahedral, square pyramidal and trigonal bipyramidal. Various weak forces, i.e. lone pair–π, π–π and CH–π interactions, play a key role in stabilizing the observed structures for complexes 1, 2 and 3. This series of complexes demonstrates that although the nitro group does not coordinate to the metal center, its presence at the 2-, 3- or 4-position of the phenyl ring has a striking effect on the dimensionality as well as the structure of the resulted coordination polymers, probably due to the participation of the nitro group in l.p.⋯π and/or C–H⋯π interactions. [Copyright &y& Elsevier]