James W. Canary

Redox-triggered chiroptical molecular switches

Efficient chiroptical molecular redox switches have been engineered that display multiple stable optically active forms, chemically reversible redox processes, and highly sensitive chiroptical responses. Systems that have been studied in this context include electro-active organic polymers, redox-active coordination complexes, and certain organic compounds that may be oxidized or reduced reversibly. Studies in this field have yielded diverse platforms that benefit from dynamic stereochemical and electronic phenomena. This tutorial review introduces basic design criteria for chiroptical molecular switches, summarizes examples, and provides an outlook for future work in the area.

Tailoring tripodal ligands for zinc sensing

Zinc plays an important role in biological processes. It is implicated in many diseases, including those affecting the brain. Imaging zinc is becoming crucial to the elucidation of zinc concentration, distribution, kinetics and functions in cells and tissues. This review highlights recent advances in the development of picolylamine-based tripodal compounds as zinc sensors, especially our work in the field of sensing “invisible” Zn(II) using steady-state fluorescence, fluorescence lifetimes and chiroptical spectroscopy. Our approach has emphasized creative ligand design and detection schemes. Utilizing tris(2-pyridylmethyl)amine-based N4 tripodal ligands has provided a flexible system for engineering zinc sensors with improved sensitivity, selectivity and contrast. Also included are results with tripodal ligands that have focused more on applications.

A simple method for the determination of enantiomeric excess and identity of chiral carboxylic acids.

The association between an achiral copper(II) host (1) and chiral carboxylate guests was studied using exciton-coupled circular dichroism (ECCD). Enantiomeric complexes were created upon binding of the enantiomers of the carboxylate guests to the host, and the sign of the resultant CD signal allowed for determination of the configuration of the studied guest. The difference in magnitudes and shapes of the CD signals, in conjunction with linear discriminant analysis (LDA), allowed for the identity of the guest to be determined successfully. A model was created for the host-guest complexes which successfully predicts the sign of the observed CD signal. Further, Taft parameters were used in the model, leading to rationalization of the observed magnitudes of the CD signals. Finally, the enantiomeric excess (ee) of unknown samples of three chiral carboxylic acid guests was determined with an average absolute error of ±3.0%.

Electrospray mass spectrometry and X-ray crystallography studies of divalent metal ion complexes of tris (2-pyridylmethyl) amine

Abstract Coordination complexes of tris(2-pyridylmethyl)amine (TPA) were prepared and characterized including [Zn(TPA)X]ClO4 (X = Cl, Br, I), [Cu(TPA)Br]ClO4, [Cd(TPA)Br2], [Cd(TPA) (H2O) (NO3]NO3, [Cd(TPA)I2], [Co9TPA)Cl2], [Fe(TPA)Cl2] and [Mn(TPA) Cl2] The solid-state structures of Zn(TPA)ClClO4 (monoclinic space group, P2 1 /c; a = 14.733(3), b = 9.408(2), c = 29.722(4) A , β=90.65(1)°; V=4119(1) A 3 ; Z=8, Zn(TPA)IClO4 (triclinic space group, P1; a = 14.435(3), b = 17.69(4), c = 9.745(2) A , α=100.36(2), β=91.40(2), γ=114.62(1)°; V=2134(2) A 3 ; Z=4) and Cu(TPA)BrClO4 (monoclinic space group, P21/c; a=14.555(3), b=9.519(2), c=30.024(3) A , β=91.66(1)°; V=4158(1) A 3 ; Z=8), contain trigonal bypyramidal metal ions with halide coordinated in an apical position. The X-ray structure of [Cd(TPA)(H2O)(NO3)]NO3 (monoclinic space group, P21/n; a=15.415(4), b=9.333(2), c=17.429(4) a , β=99.39(2)° ; V=2474(2) A 3 ; Z=4) contains a seven-coordinate cadmium ion including a bidentate nitrate anion and a water molecule as ligands. The X-ray structure of [Cd(TPA)I2] (monoclinic space group, P21/n; a=10.383(2), b=13.813(2), c=15.391(1) A , β=106.07(1)° ; V=2121.1(5) A 3 ; Z=4) contains a cadmium ion with an approximately octahedral geometry. In this structure, the TPA ligand is conformationally distorted in order to accomodate the octahedral coordination geometry. The convenient new technique, electrospray mass spectrometry (ESI-MS), provided mass spectra consistent with X-ray and spectroscopic data. Mass analysis of solutions containing added competing anions was also consistent with solution data.

Redox-Switched Exciton-Coupled Circular Dichroism: A Novel Strategy for Binary Molecular Switching

Intense chiroptical properties and efficient reversibility of the chemical redox cycle support the adaptability of the CuI /CuII complex system 1/2 for the development of a binary molecular device. Reduction proceeds with ascorbic acid, and oxidation with ammonium persulfate.

A redox-reconfigurable, ambidextrous asymmetric catalyst.

A redox-reconfigurable catalyst derived from L-methionine and incorporating catalytic urea groups has been synthesized. This copper complex catalyzes the enantioselective addition of diethyl malonate to trans-β-nitrostyrene. Either enantiomer of the product can be predetermined by selection of the oxidation state of the copper ion. Enantiomeric excesses of up to 72% (S) and 70% (R) were obtained in acetonitrile. The ability of the catalyst to invert enantiomeric preference was reproduced with several different solvents and bases. Facile interconversion between the Cu(2+) and Cu(+) redox states allowed easy access to both active helical forms of the complex and, therefore, dial-in enantioselectivity.

Combining Aminocyanine Dyes with Polyamide Dendrons: A Promising Strategy for Imaging in the Near-Infrared Region

Cyanine dyes are known for their fluorescence in the near-IR (NIR) region, which is desirable for biological applications. We report the synthesis of a series of aminocyanine dyes containing terminal functional groups such as acid, azide, and cyclooctyne groups for further functionalization through, for example, click chemistry. These aminocyanine dyes can be attached to polyfunctional dendrons by copper-catalyzed azide alkyne cycloaddition (CuAAC), strain-promoted azide alkyne cycloaddition (SPAAC), peptide coupling, or direct S(NR)1 reactions. The resulting dendron-dye conjugates were obtained in high yields and displayed high chemical stability and photostability. The optical properties of the new compounds were studied by UV/Vis and fluorescence spectroscopy. All compounds show large Stokes shifts and strong fluorescence in the NIR region with high quantum yields, which are optimal properties for in vivo optical imaging.

STEREOSELECTIVE SYNTHESIS OF SQUALAMINE DESSULFATE

Abstract Squalamine dessulfate (24 R ) and the unnatural product squalamine dessulfate (24 S ) have been synthesized from stigmasterol. The key step in establishing the C24 stereochemistry is attachment of the sidechain at C22 using either (2 R )- or (2 S )-1,2-epoxy-3-methylbutane to yield the cholesteryl precursors of the epimeric squalamine dessulfates.

Absolute configurational assignment of self-organizing asymmetric tripodal ligand-metal complexes

The solution configuration of labile coordination complexes may be difficult to determine, even in cases in which the solid state structure is known. We have previously synthesized a series of chiral ligands which form pseudo-C3-symmetric complexes with ZnII and CuII salts that possess an available electrophilic coordination site. Molecular modeling of ZnII complexes of the chiral ligand N,N-bis[(2-quinolyl)methyl]-1-(2-pyridyl)ethanamine (alpha-MeBQPA) showed that the spatial arrangement of the heterocyclic arms is controlled by a substituent on one methylene arm, resulting in the adoption of an enantiomeric conformation displaying a propeller-like asymmetry. In this paper we report the application of the exciton chirality method to the determination of the conformation of asymmetric metal-ligand complexes in solution. There is a good correlation between the predicted and the observed Cotton effects, demonstrating that the geometry in solution closely resembles that predicted by computational simulations and those obtained by X-ray crystallographic studies of metal complexes with racemic and enantiomerically pure ligands. The X-ray crystallographic structure of the first optically pure complex in this series is reported.

Amyloid fibrils nucleated and organized by DNA origami constructions

Amyloid fibrils are ordered, insoluble protein aggregates that are associated with neurodegenerative conditions such as Alzheimer’s disease1. The fibrils have a common rod-like core structure, formed from an elongated stack of β-strands, and have a rigidity similar to silk (Young’s modulus of 0.2-14 Gpa)2. They also exhibit high thermal and chemical stability3, and can be assembled in vitro from short synthetic non-disease-related peptides4,5. As a result, they are of significant interest in the development of self-assembled materials for bionanotechnology applications6. Synthetic DNA molecules have previously been used to form intricate structures and organize other materials such as metal nanoparticles7,8, and could in principle be used to nucleate and organize amyloid fibrils. Here we show that DNA origami nanotubes can sheathe amyloid fibrils formed within them. The fibrils are built by modifying the synthetic peptide fragment corresponding to residues 105-115 of the amyloidogenic protein transthyretin (TTR)9, and a DNA origami10 construct is used to form 20-helix DNA nanotubes with sufficient space for the fibrils inside. Once formed, the fibril-filled nanotubes can be organized onto predefined two-dimensional platforms via DNA-DNA hybridization interactions.