Nicola Demitri

Vitamin B12: unique metalorganic compounds and the most complex vitamins.

The chemistry and biochemistry of the vitamin B12 compounds (cobalamins, XCbl) are described, with particular emphasis on their structural aspects and their relationships with properties and function. A brief history of B12, reveals how much the effort of chemists, biochemists and crystallographers have contributed in the past to understand the basic properties of this very complex vitamin. The properties of the two cobalamins, the two important B12 cofactors Ado- and MeCbl are described, with particular emphasis on how the Co-C bond cleavage is involved in the enzymatic mechanisms. The main structural features of cobalamins are described, with particular reference to the axial fragment. The structure/property relationships in cobalamins are summarized. The recent studies on base-off/base-on equilibrium are emphasized for their relevance to the mode of binding of the cofactor to the protein scaffold. The absorption, transport and cellular uptake of cobalamins and the structure of the B12 transport proteins, IF and TC, in mammals are reviewed. The B12 transport in bacteria and the structure of the so far determined proteins are briefly described. The currently accepted mechanisms for the catalytic cycles of the AdoCbl and MeCbl enzymes are reported. The structure and function of B12 enzymes, particularly the important mammalian enzymes methyltransferase (MetH) and methyl-malonyl-coenzymeA mutase (MMCM), are described and briefly discussed. Since fast proliferating cells require higher amount of vitamin B12 than that required by normal cells, the study of B12 conjugates as targeting agents has recently gained importance. Bioconjugates have been studied as potential agents for delivering radioisotopes and NMR probes or as various cytotoxic agents towards cancer cells in humans and the most recent studies are described. Specifically, functionalized bioconjugates are used as “Trojan horses” to carry into the cell the appropriate antitumour or diagnostic label. Possible future developments of B12 work are summarized.

Air-stable organic semiconductors based on 6,6′-dithienylindigo and polymers thereof

Herein we report on the synthesis and properties of 6,6′-dithienylindigo (DTI), as well as its solubilized N,N′-di(tert-butoxy carbonyl) derivative (tBOC-DTI). tBOC-DTI can be electropolymerized and thermally interconverted into films of poly(DTI). Thin films of DTI afford quasi-reversible 2-electron reduction and oxidation electrochemistry, and demonstrate ambipolar charge transport in organic field-effect transistors with a hole mobility of up to 0.11 cm2 V−1 s−1 and an electron mobility of up to 0.08 cm2 V−1 s−1. Operation of the p-channel shows excellent air stability, with minimal degradation over a 60 day stressing study. Poly(DTI) can be reversibly oxidized and reduced over hundreds of cycles while remaining immobilized on the working electrode surface, and additionally shows a pronounced photoconductivity response in a diode device geometry. This work shows the potential of extended indigo derivatives for organic electronic applications, demonstrating impressive stability under ambient conditions.

Multi-modal sensing in spin crossover compounds

We exploited the solvatochromic spin-state switching in a spin crossover (SCO) compound based on the FeII complex and the simultaneous change of spectroscopic properties for selective multimodal sensing of methanol and ethanol. We demonstrate that sensing capabilities are due to the inclusion of methanol or ethanol molecules into the crystalline structure, which tailors simultaneously the transition temperature, colour, birefringence and vibrational modes. We exploited this capability by integrating a neutral compound, switchable at room temperature, into a micrometric TAG sensitive to the colour and birefringence. The system was characterised by optical microscopy, magnetic susceptibility, Raman spectroscopy and X-ray diffraction.

Extended O-Doped Polycyclic Aromatic Hydrocarbons.

Abstract The synthesis of O‐doped benzorylenes, in which peripheral carbon atoms have been replaced by oxygen atoms, has been achieved for the first time. This includes key high‐yielding ring‐closure steps which, through intramolecular C−O bond formation, allow stepwise planarization of oligonaphthalenes. Single‐crystal X‐ray diffraction showed that the tetraoxa derivative forms remarkable face‐to‐face π–π stacks in the solid state, a favorable solid‐state arrangement for organic electronics.

A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels.

Significance Cyclic nucleotide-gated (CNG) channels underlie sensory transduction in photoreceptors and olfactory epithelium and share a high degree of homology with K+ channels. However, these channels conduct Na+ and K+ differently: although K+ channels discriminate with high accuracy Na+ from K+, CNG channels do not discriminate among different cations. By combining electrophysiology, molecular dynamics simulations, and X-ray crystallography we found that the pore region exhibits a dynamic structure. We show that (i) the selectivity filter can adapt to large and small ions with a different geometry and (ii) the pore diameter critically depends on the ion within. We conclude that the pore of CNG channels is highly flexible and that this flexibility is at the basis of their poor ionic selectivity. Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K+ channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na+, Cs+, and dimethylammonium (DMA+), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels.

Tailoring Colors by O Annulation of Polycyclic Aromatic Hydrocarbons

Abstract The synthesis of O‐doped polyaromatic hydro‐ carbons in which two polycyclic aromatic hydrocarbon sub units are bridged through one or two O atoms has been achieved. This includes high‐yield ring‐closure key steps that, depending on the reaction conditions, result in the formation of furanyl or pyranopyranyl linkages through intramolecular C−O bond formation. Comprehensive photophysical measurements in solution showed that these compounds have exceptionally high emission yields and tunable absorption properties throughout the UV/Vis spectral region. Electrochemical investigations showed that in all cases O annulation increases the electron‐donor capabilities by raising the HOMO energy level, whereas the LUMO energy level is less affected. Moreover, third‐order nonlinear optical (NLO) measurements on solutions or thin films containing the dyes showed very good values of the second hyperpolarizability. Importantly, poly(methyl methacrylate) films containing the pyranopyranyl derivatives exhibited weak linear absorption and NLO absorption compared to the nonlinearity and NLO refraction, respectively, and thus revealed them to be exceptional organic materials for photonic devices.

Trans and cis influences and effects in cobalamins and in their simple models.

The interligand interactions in coordination compounds have been principally interpreted in terms of cis and trans influences and effects, which can be defined as the ability of a ligand X to affect the bond of another ligand, cis or trans to X, to the metal. This review analyzes these effects/influences in cobalamins (XCbl) and their simple models cobaloximes, LCo(chel)X. Important properties of these complexes, such as geometry, stability, and reactivity, can be rationalized in terms of steric and electronic factors of the ligands. Experimental evidence of normal and inverse trans influence is described in alkylcobaloximes for the first time. The study of simple B(12) models has complemented that on the more complex cobalamins, with particular emphasis on the properties of the axial L-Co-X moiety. Some of the conclusions reached for the axial fragment of simple models have also been qualitatively detected in cobalamins and have furnished new insight into the as yet unestablished mechanism for the homolytic cleavage of the Co - C bond in the AdoCbl-based enzymes.

Phosphonium-based tetrakis dibenzoylmethane Eu(III) and Sm(III) complexes: synthesis, crystal structure and photoluminescence properties in a weakly coordinating phosphonium ionic liquid

Highly luminescent anionic Ln(III) β-diketonate complexes of the formula [P8,8,8,1][Ln(dbm)4], with Ln = Eu3+ and Sm3+, [P8,8,8,1] = trioctylmethylphosphonium and dbm = 1,3-diphenylpropane-1,3-dione were synthesized. The single crystal X-ray structure of the samarium and europium complexes showed that the metal ion was surrounded by four ligands and that no water or solvent molecules were coordinated. The solid complexes showed good thermal stability up to 250 °C. The complexes easily dissolved in the ionic liquid trioctylmethylphosphonium bis(trifluoromethylsulfonyl)imide [P8,8,8,1][Tf2N], due to the presence of a common phosphonium countercation in the ionic liquid and in the Eu(III) and Sm(III) complexes. The photoluminescence of the complexes was studied in the solid state and in an ionic liquid as well as in acetonitrile (MeCN) as a solvent.

Rational Synthesis of AB-Type N-Substituted Core-Functionalized Naphthalene Diimides (cNDIs)

Acid-mediated transformation of tetraethyl 2,6-diethoxynaphthalene-1,4,5,8-tetracarboxylate selectively affords the core-substituted naphthalene-anhydride-ester (cNAE) in quantitative yield. This anhydride can be selectively converted into hetero-N-substituted core-functionalized naphthalene diimides (cNDIs) through sequential condensation reactions in the presence of the precursor amine with very high isolated yields over four steps. The approach can be applied to prepare a large variety of heterocyclic, aromatic, and aliphatic heterodiimides.

Pd-catalyzed Z-selective semihydrogenation of alkynes: determining the type of active species

A protocol was developed to distinguish between well‐defined molecular and nanoparticle‐based catalysts for the Pd‐catalyzed semihydrogenation reaction of alkynes to Z‐alkenes. The protocol applies quantitative partial poisoning and dynamic light scattering methods, which allow the institution of additional validation experiments. For the quantitative partial poisoning method, tetramethylthiourea (TMTU) was developed as an alternative for the standard poison ligand CS2, and was found to be superior in its applicability. The protocol and the TMTU poison ligand were validated using the well‐described [PdII(phenanthroline)]‐catalyzed copolymerization of styrene and CO, confirming that this system is clearly operating as a well‐defined molecular catalyst. The protocol was subsequently applied to three catalyst systems used for the semihydrogenation of alkynes. The first was proposed to be a molecular [Pd0(IMes)] catalyst that uses molecular hydrogen, but the data gathered for this system, following the new protocol, clearly showed that nanoparticles (NPs) are catalytically active. The second catalyst system studied was an N‐heterocyclic carbene (NHC) Pd system for transfer semihydrogenation using formic acid as the hydrogen source, which was proposed to operate through an inu2005situ generated molecular [Pd0(IMes)] catalyst in earlier studies. The investigations showed that only a small fraction of the Pd added becomes active in the catalytic reaction and that NPs are formed. However, despite these findings, a clear distinction between catalytic activity of NPs versus a molecular catalyst could not be made. The third investigated system is based on a [PdII(IMes)(η3‐allyl)Cl] precatalyst with additive ligands. The combined data gathered for this system are multi‐interpretable, but suggest that a partially deactivated molecular catalyst dominates in this reaction.