Fifty Shades of Phenanthroline: Synthesis Strategies to Functionalize 1,10-Phenanthroline in All Positions.

1,10-Phenanthroline (phen) is one of the most popular ligands ever used in coordination chemistry due to its strong affinity for a wide range of metals with various oxidation states. Its polyaromatic structure provides robustness and rigidity, leading to intriguing features in numerous fields (luminescent coordination scaffolds, catalysis, supramolecular chemistry, sensors, theranostics, etc.). Importantly, phen offers eight distinct positions for functional groups to be attached, showcasing remarkable versatility for such a simple ligand. As a result, phen has become a landmark molecule for coordination chemists, serving as a must-use ligand and a versatile platform for designing polyfunctional arrays. The extensive use of substituted phenanthroline ligands with different metal ions has resulted in a diverse array of complexes tailored for numerous applications. For instance, these complexes have been utilized as sensitizers in dye-sensitized solar cells, as luminescent probes modified with antibodies for biomaterials, and in the creation of elegant supramolecular architectures like rotaxanes and catenanes, exemplified by Sauvage's Nobel Prize-winning work in 2016. In summary, phen has found applications in almost every facet of chemistry. An intriguing aspect of phen is the specific reactivity of each pair of carbon atoms ([2,9], [3,8], [4,7], and [5,6]), enabling the functionalization of each pair with different groups and leading to polyfunctional arrays. Furthermore, it is possible to differentiate each position in these pairs, resulting in non-symmetrical systems with tremendous versatility. In this Review, the authors aim to compile and categorize existing synthetic strategies for the stepwise polyfunctionalization of phen in various positions. This comprehensive toolbox will aid coordination chemists in designing virtually any polyfunctional ligand. The survey will encompass seminal work from the 1950s to the present day. The scope of the Review will be limited to 1,10-phenanthroline, excluding ligands with more intracyclic heteroatoms or fused aromatic cycles. Overall, the primary goal of this Review is to highlight both old and recent synthetic strategies that find applicability in the mentioned applications. By doing so, the authors hope to establish a first reference for phenanthroline synthesis, covering all possible positions on the backbone, and hope to inspire all concerned chemists to devise new strategies that have not yet been explored.

Copper(I) Bis(diimine) Complexes with High Photooxidation Power: Reductive Quenching of the Excited State with a Benzimidazoline Sacrificial Donor.

The reductive quenching of photoexcited photosensitizers is a very efficient way to achieve challenging reduction reactions. In this process, the excited photosensitizer is reduced by a sacrificial electron donor. This mechanism is rarely observed with copper(I) bis(diimine) complexes, which are nevertheless acknowledged as very promising photosensitizers. This is due to the fact that they are very poor photooxidants and prove unable to react with common donors once promoted in their excited state. In this article, we evidence the rare reductive quenching cycle with two specially designed copper(I) complexes. These complexes exhibit improved photooxidation power thanks to an optimized coordination sphere made of strongly π-accepting ligands. Reductive quenching of the excited state of the latter complexes with a classical benzimidazoline sacrificial donor is monitored, and reduced complexes are accumulated during prolonged photolysis. Trials to utilize the photogenerated reductive power are presented.

Investigation of copper oxidation states in plasmonic nanomaterials by XAS and Raman spectroscopy.

Plasmonic core-shell-isolated nanoparticles are promising nanoplatforms for photocatalysis and for low detection analysis. This paper describes the characterization of a 2,2'-bipyridine phosphonate functionalized Ag@TiO2 nanocomposite which complexes copper ions by enhanced Raman spectroscopy and X-ray absorption (XANES and EXAFS). We distinguished Cu(i) from Cu(ii) complexes using shell-isolated nanoparticle enhanced Raman (SHINERS) combined with XAS spectroscopy.

Functionalized core-shell Ag@TiO2 nanoparticles for enhanced Raman spectroscopy: a sensitive detection method for Cu(ii) ions.

This paper demonstrates the use of surface plasmon resonance of core-shell Ag@TiO2 particles in SHINERS experiments. A copper(ii) complex grafted onto Ag@TiO2 surface was probed by Raman spectroscopy using resonance excitation profiles vs. excitation wavelengths (514, 633 and 785 nm) to tune the Raman signals. Enhancement factors of the SHINERS assembly have been estimated and compared to the SERS effect of unmodified silver NPs colloidal dispersions. Finally, the grafting of the copper(ii) complex onto Ag@TiO2 was advantageously compared to the grafting onto Ag@SiO2 shell.

Surface modification of plasmonic noble metal-metal oxide core-shell nanoparticles.

A comprehensive survey on the methods for the surface modification of plasmonic noble metal-metal oxide core-shell nanoparticles is presented. The review highlights various strategies for covalent attachment and electrostatic binding of molecules and molecular ions to core-shell nanoparticles with a focus on plasmonically active silver and gold nanoparticles encapsulated by SiO2 and TiO2 shells.

Phosphonate-Mediated Immobilization of Rhodium/Bipyridine Hydrogenation Catalysts.

RhL2 complexes of phosphonate-derivatized 2,2'-bipyridine (bpy) ligands L were immobilized on titanium oxide particles generated in situ. Depending on the structure of the bipy ligand-number of tethers (1 or 2) to which the phosphonate end groups are attached and their location on the 2,2'-bipyridine backbone (4,4'-, 5,5'-, or 6,6'-positions)-the resulting supported catalysts showed comparable chemoselectivity but different kinetics for the hydrogenation of 6-methyl-5-hepten-2-one under hydrogen pressure. Characterization of the six supported catalysts suggested that the intrinsic geometry of each of the phosphonate-derivatized 2,2'-bipyridines leads to supported catalysts with different microstructures and different arrangements of the RhL2 species at the surface of the solid, which thereby affect their reactivity.

Non-photochemical catalytic hydrolysis of methyl parathion using core-shell Ag@TiO2 nanoparticles.

Highly water-dispersible core-shell Ag@TiO2 nanoparticles were prepared and shown to be catalytically active for the rapid degradation of the organothiophosphate pesticide methyl parathion (MeP). Formation of the hydrolysis product, p-nitrophenolate was monitored at pH 7.5 and 8.0, using UV-Vis spectroscopy. 31P NMR spectroscopy confirmed that hydrolysis is the predominant pathway for substrate breakdown under non-photocatalytic conditions. We have demonstrated that the unique combination of TiO2 with silver nanoparticles is required for catalytic hydrolysis with good recyclability. This work represents the first example of MeP degradation using TiO2 doped with AgNPs under mild and ambient conditions. Analysis of catalytic data and a proposed dark mechanism for MeP hydrolysis using core-shell Ag@TiO2 nanoparticles are described.

Visible light assisted hydrogen generation from complete decomposition of hydrous hydrazine using rhodium modified TiO2 photocatalysts.

Hydrogen is considered to be an ideal energy carrier, which produces only water when combined with oxygen and thus has no detrimental effect on the environment. While the catalytic decomposition of hydrous hydrazine for the production of hydrogen is well explored, little is known about its photocatalytic decomposition. The present paper describes a highly efficient photochemical methodology for the production of hydrogen through the decomposition of aqueous hydrazine using titanium dioxide nanoparticles modified with a Rh(i) coordinated catechol phosphane ligand (TiO2-Rh) as a photocatalyst under visible light irradiation. After 12 h of visible light irradiation, the hydrogen yield was 413 µmol g-1 cat with a hydrogen evolution rate of 34.4 µmol g-1 cat h-1. Unmodified TiO2 nanoparticles offered a hydrogen yield of 83 µmol g-1 cat and a hydrogen evolution rate of only 6.9 µmol g-1 cat h-1. The developed photocatalyst was robust under the experimental conditions and could be efficiently reused for five subsequent runs without any significant change in its activity. The higher stability of the photocatalyst is attributed to the covalent attachment of the Rh complex, whereas the higher activity is believed to be due to the synergistic mechanism that resulted in better electron transfer from the Rh complex to the conduction band of TiO2.

Comparison of Zirconium Phosphonate-Modified Surfaces for Immobilizing Phosphopeptides and Phosphate-Tagged Proteins.

Different routes for preparing zirconium phosphonate-modified surfaces for immobilizing biomolecular probes are compared. Two chemical-modification approaches were explored to form self-assembled monolayers on commercially available primary amine-functionalized slides, and the resulting surfaces were compared to well-characterized zirconium phosphonate monolayer-modified supports prepared using Langmuir-Blodgett methods. When using POCl3 as the amine phosphorylating agent followed by treatment with zirconyl chloride, the result was not a zirconium-phosphonate monolayer, as commonly assumed in the literature, but rather the process gives adsorbed zirconium oxide/hydroxide species and to a lower extent adsorbed zirconium phosphate and/or phosphonate. Reactions giving rise to these products were modeled in homogeneous-phase studies. Nevertheless, each of the three modified surfaces effectively immobilized phosphopeptides and phosphopeptide tags fused to an affinity protein. Unexpectedly, the zirconium oxide/hydroxide modified surface, formed by treating the amine-coated slides with POCl3/Zr(4+), afforded better immobilization of the peptides and proteins and efficient capture of their targets.

Design and optimization of a phosphopeptide anchor for specific immobilization of a capture protein on zirconium phosphonate modified supports.

The attachment of affinity proteins onto zirconium phosphonate coated glass slides was investigated by fusing a short phosphorylated peptide sequence at one extremity to enable selective bonding to the active surface via the formation of zirconium phosphate coordinate covalent bonds. In a model study, the binding of short peptides containing zero to four phosphorylated serine units and a biotin end-group was assessed by surface plasmon resonance-enhanced ellipsometry (SPREE) as well as in a microarray format using fluorescence detection of AlexaFluor 647-labeled streptavidin. Significant binding to the zirconated surface was only observed in the case of the phosphopeptides, with the best performance, as judged by streptavidin capture, observed for peptides with three or four phosphorylation sites and when spotted at pH 3. When fusing similar phosphopeptide tags to the affinity protein, the presence of four phosphate groups in the tag allows efficient immobilization of the proteins and efficient capture of their target.

Facile P,N-heterocycle synthesis via tandem aminomethylation-cyclization of H-phosphinate building blocks.

Various heterocycles containing phosphorus and nitrogen are easily synthesized from readily available H-phosphinate building blocks. Aminomethylation of these H-phosphinates is followed by in situ cyclization through substitution or cross-coupling to produce novel heterocycles in moderate to good yields.

Synthesis of P,N-heterocycles from omega-amino-H-phosphinates: conformationally restricted alpha-amino acid analogs.

P,N-heterocycles (3-hydroxy-1,3-azaphospholane and 3-hydroxy-1,3-azaphosphorinane-3-oxide) are synthesized in moderate yield from readily available omega-amino-H-phosphinates and aldehydes or ketones via an intramolecular Kabachnik-Fields reaction. The products are conformationally restricted phosphinic analogs of alpha-amino acids. The multigram-scale syntheses of the H2N(CH2)(n)PO2H2 phosphinic precursors (n = 1, 2, 3) and some derivatives are also described.

Synthesis and antiviral properties of some polyphenols related to Salvia genus.

An efficient synthesis of the acid part of salvianolic acid E 2 is described. Compound 2 was obtained from vanillin in 10 steps and 21% overall yield. During the synthesis of 2 an unexpected 5-oxo-4b,9b-dihydroindano[1,2-b]benzofuran rac-12 was isolated. Both compounds together with the acid part of salvianolic acid D were active as HIV-1 integrase inhibitors at the submicromolar level. But they did not inhibit the replication of the virus on MT-4 cells.

The total synthesis of fukiic acid, an HIV-1 integrase inhibitor.

A successful synthesis of fukiic acid is described in 7% overall yield (6 steps from veratraldehyde). rac-Fukiic acid was found to be a potent inhibitor of HIV-1 integrase but did not reveal any antiviral activity in the MT-4 cells assay.

Synthesis and biological activities of a series of 4,5-diaryl-3-hydroxy-2(5H)-furanones.

A series of thirteen 4,5-diaryl-3-hydroxy-2(5H)-furanones were synthesized. They were evaluated for their antioxidant potencies and inhibitory properties of 5-lipoxygenase, cyclooxygenases, HIV-1 integrase and PC3 cell proliferation. New hits were discovered either in the anti-proliferation test or in the HIV anti-integrase test.

Synthesis and HIV-1 integrase inhibitory activities of caffeic acid dimers derived from Salvia officinalis.

The synthesis of two caffeoyl-coumarin conjugates, derived from sagecoumarin, has been accomplished, starting from ferulic acid, isoferulic acid and sesamol. Both compounds exhibited potent inhibitory activities at micromolar concentrations against HIV-1 integrase in 3'-end processing reaction but were less effective against HIV-1 replication in a single-round infection assay of HeLa-beta-gal-CD4+ cells.