Metal induced folding: Synthesis and conformational analysis of the lanthanide complexes of two 44-membered hydrazone macrocycles

Six new lanthanide complexes of two 44-membered macrocycles have been prepared and characterised in solution. An analysis of the conformations of the free macrocycles and their lanthanide complexes both in solution (2D NMR) and in solid state (X-ray crystallography) demonstrate that the complexation induces changes in folding of the macrocycles

Development of a Bead-Based Multiplex Genotyping Method for Diagnostic Characterization of HPV Infection

The accurate genotyping of human papillomavirus (HPV) is clinically important because the oncogenic potential of HPV is dependent on specific genotypes. Here, we described the development of a bead-based multiplex HPV genotyping (MPG) method which is able to detect 20 types of HPV (15 high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 5 low-risk HPV types 6, 11, 40, 55, 70) and evaluated its accuracy with sequencing. A total of 890 clinical samples were studied. Among these samples, 484 were HPV positive and 406 were HPV negative by consensus primer (PGMY09/11) directed PCR. The genotyping of 484 HPV positive samples was carried out by the bead-based MPG method. The accuracy was 93.5% (95% CI, 91.0–96.0), 80.1% (95% CI, 72.3–87.9) for single and multiple infections, respectively, while a complete type mismatch was observed only in one sample. The MPG method indiscriminately detected dysplasia of several cytological grades including 71.8% (95% CI, 61.5–82.3) of ASCUS (atypical squamous cells of undetermined significance) and more specific for high grade lesions. For women with HSIL (high grade squamous intraepithelial lesion) and SCC diagnosis, 32 women showed a PPV (positive predictive value) of 77.3% (95% CI, 64.8–89.8). Among women >40 years of age, 22 women with histological cervical cancer lesions showed a PPV of 88% (95% CI, 75.3–100). Of the highest risk HPV types including HPV-16, 18 and 31 positive women of the same age groups, 34 women with histological cervical cancer lesions showed a PPV of 77.3% (95% CI, 65.0–89.6). Taken together, the bead-based MPG method could successfully detect high-grade lesions and high-risk HPV types with a high degree of accuracy in clinical samples

Host–guest assembly of ligand systems for metal ion complexation. Synergistic solvent extraction of copper(II) and silver(I) by 1,4,8,11-tetrabenzyl-1,4,8,11-tetraazacyclodecane in combination with carboxylic acids

Host–guest formation between 1,4,8,11-tetrabenzyl-1,4,8,11-tetraazacyclodecane (1) and lipophilic organic carboxylic acids in chloroform has been investigated and the effect of such ligand assembly on the solvent extraction of copper(II) and silver(I) has been probed. NMR titration experiments in the absence of a metal ion confirm the formation of weak 1 ∶ 1 and 1 ∶ 2 (macrocycle ∶ carboxylic acid) assemblies in CDCl3 between 1 and palmitic (hexadecanoic) acid or 4-tert-butylbenzoic acid while difunctional salicylic acid showed a 1 ∶ 2 interaction that is somewhat stronger. The interaction between the former two acids and the tetra-N-benzylated macrocycle is significantly less than that reported previously for its non-substituted parent, cyclam; a result that likely reflects the presence of the less-basic, more sterically hindered tertiary nitrogens in 1 relative to the secondary nitrogens present in cyclam. Carboxylic acid-containing assemblies of this type have been used as extractants in a series of solvent extraction (water/chloroform) experiments. From both previous observations as well as from entropy considerations, it was anticipated that the use of a host–guest assembly of the above type for metal-ion complexation might contribute to enhanced metal ion binding (and concomitant enhanced metal ion extraction). Such behaviour is postulated to arise from the components of the coordination sphere being, at least in part, assembled for complex formation. In accord with this, the use of the ligand assembly involving palmitic acid/macrocycle 1 was found to lead to enhanced (synergistic) extraction of copper(II) at a metal ion concentration of 10−3 mol dm−3 while, for silver(I), synergism was somewhat marginal at this concentration but was clearly apparent under related conditions when the silver concentration was reduced to 10−4 mol dm−3. Similar behaviour towards silver was also observed when 4-tert-butylbenzoic acid was substituted for palmitic acid, while the use of salicylic acid resulted in enhanced (synergistic) extraction at both metal ion concentrations

Synergistic solvent extraction of Co(II), Ni(II), Cu(II) and Zn(II) based on supramolecular assemblies

The aim of the studies now reported was to investigate synergistic extraction of Co(II), Ni(II), Cu(II) and Zn(II) with a mixed ligand system consisting of a macrocyclic amine and an organic acid. A key design feature of such mixed extractant systems is their ability to form supramolecular assemblies which are preorganized for metal complexation and which are able to reversibly transfer metal cations from an aqueous feed solution. Experiments were performed to elucidate the inter-dependence of the extraction behaviour on the metal ion type, the nature of the diluent as well as the concentration ratio of both extractants, and the pH of the aqueous solution. Furthermore, an NMR titration study of assembly formation in solution and an X-ray structure of a relevant crystallized ligand adduct have been obtained in order to aid understanding of the observed solvent extraction results

Synergistic solvent extraction of Co(II), Ni(II), Cu(II) and Zn(II) based on supramolecular assemblies

The aim of the studies now reported was to investigate synergistic extraction of Co(II), Ni(II), Cu(II) and Zn(II) with a mixed ligand system consisting of a macrocyclic amine and an organic acid. A key design feature of such mixed extractant systems is their ability to form supramolecular assemblies which are preorganized for metal complexation and which are able to reversibly transfer metal cations from an aqueous feed solution. Experiments were performed to elucidate the inter-dependence of the extraction behaviour on the metal ion type, the nature of the diluent as well as the concentration ratio of both extractants, and the pH of the aqueous solution. Furthermore, an NMR titration study of assembly formation in solution and an X-ray structure of a relevant crystallized ligand adduct have been obtained in order to aid understanding of the observed solvent extraction results

Anion selectivity in zwitterionic amide-funtionalised metal salt extractants

Amide-functionalised salen ligands capable of extracting metal salts have been synthesised and characterised. Single-crystal X-ray structure determinations of complexes of NiSO4, [Ni(L)(SO4)], confirm that the ionophores are in a zwitterionic form with Ni-IIbound in the deprotonated salen moiety and the SO42- ion associated with protonated pendant N'-amidopiperazine groups. Treatment of [N'(L)(SO4)] with base removes the protons from the pendant amido-amine group resulting in loss of the SO42- ion and formation of metal-only complexes of type [Ni(L-2H)], which have been characterized by single-crystal X-ray diffraction. Three of the ligands with solubilities suitable for solvent extraction studies show loading and stripping pH-profiles that are suitable for the recovery of CuSO4 or CuCl2 from industrial leach solutions. The copper-only complexes, [Cu(L-2H)], are selective for Cl- over SO42- in both solvent extraction and bulk liquid membrane transport experiments and were found to bind Cl- in two steps via the formation of a 1:1:1 [Cu(L-H)Cl] assembly, followed by a 1:1:2 [Cu(L)Cl-2] assembly as the pH of the aqueous phase is lowered. The anion transport selectivity was evaluated for a number of other mono-charged anions and interestingly the ligands were found to display a preference for the Br- ion. To probe the influence of the Hofmeister bias on the selectivity of anion complexation, single-phase potentiometric titration experiments were employed to investigate the binding of SO42- and Cl- by one of the copper only complexes, [Cu(L-2H)] in 95%/5% MeOH/water. Under these conditions selectivity was reversed (SO42- > Cl-) confirming that the Hofmeister bias, which reflects the relative hydration energies of the anions, dominates the selectivity of anion extraction from aqueous media into CHCl3