Alexis D. C. Parenty

Spontaneous assembly and real-time growth of micrometre-scale tubular structures from polyoxometalate-based inorganic solids

We report the spontaneous and rapid growth of micrometre-scale tubes from crystals of a metal oxide-based inorganic solid when they are immersed in an aqueous solution containing a low concentration of an organic cation. A membrane immediately forms around the crystal, and this membrane then forms micrometre-scale tubes that grow with vast aspect ratios at controllable rates along the surface on which the crystal is placed. The tubes are composed of an amorphous mixture of polyoxometalate-based anions and organic cations. It is possible for liquid to flow through the tubes, and for the direction of growth and the overall tube diameter to be controlled. We demonstrate that tube growth is driven by osmotic pressure within the membrane sack around the crystal, which ruptures to release the pressure. These robust, self-growing, micrometre-scale tubes offer opportunities in many areas, including the growth of microfluidic devices and the self-assembly of metal oxide-based semipermeable membranes for diverse applications.

Metal-mediated transformation of a triazinephenanthridinium ligand leading to a {Pd5} coordination complex observed crystallographically and by cryospray mass spectrometry.

The formation of a pentanuclear palladium(II) complex with a phenanthridinonetriazine-based ligand system, which itself is formed by a metal-mediated rearrangement of a triazinephenanthridinium proligand, is described.

Dihydroimidazophenanthridinium (DIP)‐Based DNA Binding Agents with Tuneable Structures and Biological Activity

We have synthesised a library of dihydroimidazophenanthridinium cations (DIPs) with large structural diversity (1–29) using a “one‐pot” approach. The DNA binding constants of DIPs range from 2×104 to 1.3×105 M−1, and the free energies for binding range from −5.9 to −6.40 kcal mol−1. Viscosity measurements demonstrated that the binding of the compounds caused DNA lengthening, thus signifying binding by intercalation. The cytotoxicities of the compounds were determined by tetrazolium dye‐based microtitration assays and showed a large range of values (0.09–11.7 μM). Preliminary molecular modelling studies of the DNA–DIP interactions suggested that the DIP moieties can interact with DNA by intercalation, and some R groups might facilitate binding by minor‐groove binding. The results provide insight into how to design biologically active DNA binding agents that can interact in these ways.

A new C–C bond forming annulation reaction leading to pH switchable heterocycles

A C-C bond forming reaction resulting from the alpha-addition of carbon based nucleophiles to N-bromoethyl phenanthridinium leads to the formation of 2,3-dihydro-12H-pyrrolo[1,2-f]phenanthridine-based derivatives which undergo reversible ring-opening/closing under pH control.

Fine Tuning Reactivity: Synthesis and Isolation of 1,2,3,12b-Tetrahydroimidazo[1,2-f]phenanthridines

A facile route for the synthesis and isolation of 1,2,3,12b-tetrahydroimidazo[1,2-f]phenanthridines (TIPs) has been developed. The heterocycle is a reactive intermediate in the three-step cascade synthesis of 2,3-dihydro-1H-imidazo[1,2-f]phenanthridinium cations (DIPs), a biologically active DNA intercalating framework; however, the intermediate has previously only been characterized in situ. Derivatization of the structure at the imidazo-N position controls the reactivity of the intermediate with respect to electronic potential and pK(a) allowing isolation of a selection of TIP structures. Correlations between these parameters and reaction outcome have been made, and other influences such as steric and solvent effects have also been investigated.

Supramolecular self-assembly and anion-dependence of copper(II) complexes with cationic dihydro-imidazo phenanthridinium (DIP)-containing ligands

We present two new ligands, 2,3-dihydro-1-(2-pyridyl-methyl)-imidazo[1,2-f]phenanthridinium bromide (L1·Br) and 2,3-dihydro-1-(4-pyridyl-methyl)-imidazo[1,2-f]phenanthridinium bromide (L2·Br), which have been synthesized and fully characterized as coordinating cations. The reactions of Cu(BF4)2 (compound 1), Cu(NO3)2 (compound 2), CuBr2 (compound 3), Cu(NO3)2 and NaN3 (compound 4), Cu(NO3)2 and NaSCN (compound 5) with L1·Br and CuBr2 with L2·Br (compound 6) have been carried out. The crystal structures of the resulting metal–organic assemblies have been determined and the intermolecular interactions of the compounds in the crystalline phase have been analysed. A mononuclear copper(II) compound has been obtained with CuBr2, in which the copper(II) ion adopts a tetrahedral geometry with a CuNBr3 coordination motif. With Cu(BF4)2, two L1+ cations and two bromide anions chelate the copper ion giving a CuN2Br2 motif, while the BF4− is present as a non-coordinating counterion. With Cu(NO3)2, a five coordinated copper complex is obtained whereas when bridging ligands such as NaN3 and NaSCN are added into the reaction mixture of L1·Br and Cu(NO3)2, two novel dinuclear copper coordination cores of [Cu2(μ1,1-N3)2(N3)4]2− and Cu(CH3O)2(SCN)4]2− form. The presence of the large heteroaromatic cationic DIP moiety within the ligand system leads to the formation of 1-, 2- and 3-D supramolecular arrays based on the interactions of the π systems between adjacent molecules.

Does it bind? An instant binding assay for DNA oligonucleotide interactive small molecules

Ultrafiltration analysis has been used to screen DNA oligonucleotide interactive small molecules for the first time, providing an almost instantaneous indication of the binding affinity, and was used to identify a new class of DNA interactive molecules based on a range of dihydro-imidazo-phenanthridinium-based framework; this methodology provides a straightforward yes/no answer to small molecule DNA binding.