Andrei Loas

Synthesis, X-ray Structure, Magnetic Resonance, and DFT Analysis of a Soluble Copper(II) Phthalocyanine Lacking C-H Bonds

The synthesis, crystal structure, and electronic properties of perfluoro-isopropyl-substituted perfluorophthalocyanine bearing a copper atom in the central cavity (F(64)PcCu) are reported. While most halogenated phthalocyanines do not exhibit long-term order sufficient to form large single crystals, this is not the case for F(64)PcCu. Its crystal structure was determined by X-ray analysis and linked to the electronic properties determined by electron paramagnetic resonance (EPR). The findings are corroborated by density functional theory (DFT) computations, which agree well with the experiment. X-band continuous-wave EPR spectra of undiluted F(64)PcCu powder, indicate the existence of isolated metal centers. The electron-withdrawing effect of the perfluoroalkyl (R(f)) groups significantly enhances the complexes solubility in organic solvents like alcohols, including via their axial coordination. This coordination is confirmed by X-band (1)H HYSCORE experiments and is also seen in the solid state via the X-ray structure. Detailed X-band CW-EPR, X-band Davies and Mims ENDOR, and W-band electron spin-echo-detected EPR studies of F(64)PcCu in ethanol allow the determination of the principal g values and the hyperfine couplings of the metal, nitrogen, and fluorine nuclei. Comparison of the g and metal hyperfine values of F(64)PcCu and other PcCu complexes in different matrices reveals a dominant effect of the matrix on these EPR parameters, while variations in the ring substituents have only a secondary effect. The relatively strong axial coordination occurs despite the diminished covalency of the C-N bonds and potentially weakening Jahn-Teller effects. Surprisingly, natural abundance (13)C HYSCORE signals could be observed for a frozen ethanol solution of F(64)PcCu. The (13)C nuclei contributing to the HYSCORE spectra could be identified as the pyrrole carbons by means of DFT. Finally, (19)F ENDOR and easily observable paramagnetic NMR were found to relate well to the DFT computations, revealing negligible isotropic hyperfine (Fermi contact) contributions. The single-site isolation in solution and solid state and the relatively strong coordination of axial ligands, both attributed to the introduction of R(f) groups, are features important for materials and catalyst design.

Achieving Reversible Sensing of Nitroxyl by Tuning the Ligand Environment of Azamacrocyclic Copper(II) Complexes

To elucidate the factors that impart selectivity for nitroxyl (HNO) over nitric oxide (NO), thiols, and H2S in metal-based fluorescent probes, we investigated five Cu(II)-cyclam (14-N4) derivatives. Upon exposure to NO gas at pH 7, no changes occur in the UV-vis spectra of any of the complexes. Addition of Angelis salt to generate HNO promotes reduction of Cu(II) only in the case of [Cu(II)(14-N4-Ts)(OTf)2], which has the most positive reduction potential of the series. To gain insight into the observed reactivity, we prepared the Cu(II) complex of the mixed thia/aza 14-N2S2 ligand. [Cu(II)(14-N2S2)(OTf)2] reacts reversibly with HNO at pH 7, although nonselectively over thiols and H2S. The recurrent sensing of HNO uncovered with the study of Cu(II) azamacrocyclic complexes is a remarkable feature that opens the door for the design of a new generation of metal-based probes.

Addition of a second binding site increases the dynamic range but alters the cellular localization of a red fluorescent probe for mobile zinc.

We report the synthesis and photophysical properties of ZBR4 and ZR1, two resorufin-based ditopic probes for mobile zinc. Upon binding Zn2+, the sensors display 14- and 41-fold enhancements of their red fluorescence emission, respectively. In contrast to ZR1 and other members of the ZBR family, which accumulate in the endoplasmic reticulum, ZBR4 spontaneously localizes to the mitochondria of HeLa cells. The modular approach in designing the constructs facilitates a homologation strategy aimed at tuning the zinc-binding and intracellular targeting properties of future probes.

Direct ratiometric detection of nitric oxide with Cu(II)-based fluorescent probes

We report the first Cu(ii)-based fluorescent sensors for ratiometric detection of nitric oxide. The two probes operate by energy transfer between hydroxycoumarin and fluorescein chromophores, contain polyproline or piperazine as rigid spacers, and elicit a rapid and selective ratiometric response upon direct reaction with nitric oxide.

Tuning the Diiron Core Geometry in Carboxylate-Bridged Macrocyclic Model Complexes Affects Their Redox Properties and Supports Oxidation Chemistry

We introduce a novel platform to mimic the coordination environment of carboxylate-bridged diiron proteins by tethering a small, dangling internal carboxylate, (CH2)nCOOH, to phenol-imine macrocyclic ligands (H3PIMICn). In the presence of an external bulky carboxylic acid (RCO2H), the ligands react with [Fe2(Mes)4] (Mes = 2,4,6-trimethylphenyl) to afford dinuclear [Fe2(PIMICn)(RCO2)(MeCN)] (n = 4-6) complexes. X-ray diffraction studies revealed structural similarities between these complexes and the reduced diiron active sites of proteins such as Class I ribonucleotide reductase (RNR) R2 and soluble methane monooxygenase hydroxylase. The number of CH2 units of the internal carboxylate arm controls the diiron core geometry, affecting in turn the anodic peak potential of the complexes. As functional synthetic models, these complexes facilitate the oxidation of C-H bonds in the presence of peroxides and oxo transfer from O2 to an internal phosphine moiety.

Metalloneurochemistry and the Pierian Spring: ‘Shallow Draughts Intoxicate the Brain’

Metal ions perform critical and diverse functions in nervous system physiology and pathology. The field of metalloneurochemistry aims to understand the mechanistic bases for these varied roles at the molecular level. Here, we review several areas of research that illustrate progress toward achieving this ambitious goal and identify key challenges for the future. We examine the use of lithium as a mood stabilizer, the roles of mobile zinc and copper in the synapse, the interplay of nitric oxide and metals in retrograde signaling, and the regulation of iron homeostasis in the brain. These topics were chosen to demonstrate not only the breadth of the field, but also to highlight opportunities for discovery by studying such complex systems in greater detail. We are beginning to uncover the principles by which receptors and transmitters utilize metal ions to modulate neurotransmission. These advances have revealed exciting new insights into the intricate mechanisms that give rise to learning, memory, and sensory perception, while opening many new avenues for further exploration.

Fluoroalkyl phthalocyanines: Bioinspired catalytic materials

The design of self oxidation-resistant catalytic materials based on organic molecules, although advantageous due to the ability to control their structures, is limited by the presence of labile C–H...