Thioether Donor Research Articles

Click Chemistry for the Generation of Combination of Triazole Core and Thioether Donor Site in Organosulfur Ligands: Applications of Metal Complexes in Catalysis.

During the last two decades, organosulfur compounds have been used in the field of transition metal catalysis. Some of such compounds are known for their ability to withstand their exposure to air and moisture. These compounds are very important ligands. They may be obtained using simple and smooth modular synthetic protocols which include nucleophilic substitution reactions. The development of click chemistry represents a new era of innovation. It is a lighthouse of reliable and efficient reactions. In recent past, click chemistry has also been applied for the synthesis of such organosulfur ligands specifically suited for the dynamic field of transition metal catalysis. In order to synthesize novel compounds containing sulfur and triazole ring, click chemistry is an advantageous methodology over other approaches. This article covers the general features and uses of this methodology for the development of catalytically active organosulfur compounds. The significant advances in the design of transition metal catalytic systems utilizing such ligands, their use in the catalysis of many chemical transformations are also covered in this article. Effort has also been made to present a comparative overview of the performances of such catalysts vis-à-vis the catalysts designed commonly used ligands. Catalytic performances have been discussed thoroughly in order to identify the impact of ligand architecture on efficacy of the catalyst. Effect of reaction conditions (such as time, temperature etc.) and mechanistic aspects have also been rationalized.

The influence of thioether-substituted ligands in dicopper(II) complexes: Enhancing oxidation and biological activities

This paper describes the synthesis, structural analysis, as well as the magnetic and spectroscopic characterizations of three new dicopper(II) complexes with dinucleating phenol-based ligands containing different thioether donor substituents: aromatic (1), aliphatic (2) or thiophene (3). Temperature-dependent magnetometry reveals the presence of antiferromagnetic coupling for 1 and 3 (J = −2.27 cm−1 and -5.01 cm−1, respectively, H = -2JS1S2) and ferromagnetic coupling for 2 (J = 5.72 cm−1). Broken symmetry DFT calculations attribute this behavior to a major contribution from the dz2 orbitals for 1 and 3, and from the dx2-y2 orbitals for 2, along with the p orbitals of the oxygens. The bioinspired catalytic activities of these complexes related to catechol oxidase were studied using 3,5-di-tert-butylcatechol as substrate. The order of catalytic rates for the substrate oxidation follows the trend 1 > 2 > 3 with kcat of (90.79 ± 2.90) × 10−3 for 1, (64.21 ± 0.99) × 10−3 for 2 and (14.20 ± 0.32) × 10−3 s−1 for 3. The complexes also cleave DNA through an oxidative mechanism with minor-groove preference, as indicated by experimental and molecular docking assays. Antimicrobial potential of these highly active complexes has shown that 3 inhibits both Staphylococcus aureus bacterium and Epidermophyton floccosum fungus. Notably, the complexes were found to be nontoxic to normal cells but exhibited cytotoxicity against epidermoid carcinoma cells, surpassing the activity of the metallodrug cisplatin. This research shows the multifaceted properties of these complexes, making them promising candidates for various applications in catalysis, nucleic acids research, and antimicrobial activities.

Through the Looking Glass: Using the Lens of [SNS]-Pincer Ligands to Examine First-Row Metal Bifunctional Catalysts.

ConspectusHomogeneous catalysis is at the forefront of global efforts to innovate the synthesis of fine chemicals and achieve carbon-neutrality in energy applications. For decades, the push toward sustainable catalysis has focused on the development of first-row transition metal catalysts to supplant widespread use of precious metals. Metal-ligand cooperativity is an effective strategy to yield high-performing first-row metal molecular catalysts. Despite remarkable progress, state of the art catalysts often employ phosphorus-based ligands which are air-sensitive, potentially toxic, and on occasion offset the cost-savings of the metal. Thus, the development of simple and economical ligands composed of biomimetic donors should be a key focus that cannot be overlooked in the pursuit of sustainable catalyst candidates. This is an Account of our group's efforts to develop first-row transition metal complexes which use [SNS]-pincer ligands for bifunctional catalysis. We have synthesized two potentially tridentate ligands, one bearing an amido and two thioether donors [(SMeNSMe), L1] and one which includes thiolate, imine, and thioether donors [(SNSMe), L2], and used them as platforms upon which to explore the reaction pathways of first-row metals. The [SNS] ligand, L1, leads to formation of high-spin paramagnetic metal complexes of the type M(L1)2 in which the 6-membered ring thioether donor is hemilabile (M = Mn, Fe, Co). This allows Mn(L1)2 to function as a carbonyl hydroboration catalyst that operates by a novel hydride-free, inner-sphere reaction pathway. Exploring the reactivity of L2 with Fe and Ni revealed unique coordination chemistry and a variety of mono-, di-, tri-, and tetranuclear complexes enabled by bridging thiolates. Further studies showed L2 undergoes selective Caryl-S bond cleavage upon coordination to a metal with electron-rich phosphine donors, yielding a new (CNS)2- pincer ligand. The analogous reaction with L1 afforded a new (CNSMe)- pincer ligand via both Caryl-S and benzylic C-H bond cleavage. In an attempt to prepare Fe(L2)2, we obtained instead an Fe(N2S3) complex in which imine C-C bond formation affords a potentially hexadentate redox-active ligand. The Fe(N2S3) complex is a selective catalyst for hydroboration of aldehydes and appears to operate through a complicated mechanism. In contrast, a mechanistic study of Mn(L2)(CO)3-photocatalyzed dihydroboration of nitriles indicated that both the flexibility of the κ3-SNSMe ligand (fac- vs mer-coordination) and ability of Mn to undergo a spin-state change are required to access low energy barriers for this transformation. To effectively compare the reactivity of the thiolate vs amido donor, we prepared two Cu complexes, Cu(L1)(IPr) and Cu(L2)(IPr) [IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene], showing that, while both served as carbonyl hydroboration catalysts, only the amido complex was an effective catalyst for carbonyl hydrosilylation. In addition, complexes of the type Zn(L1)2, Zn(L2)2, and Zn(L1)(L2), were also effective for catalytic carbonyl hydroboration. While Zn(L1)(L2) was most active, catalyst speciation studies showed that each undergoes bifunctional catalyst activation to form a Zn bis(alkoxide) catalyst. Overall, our observations using [SNS] ligands with first-row transition metals show how the absence of traditional phosphine donors leads to different fundamental reactivity. Furthermore, this Account demonstrates the gap of knowledge which exists in understanding the reactivity of sulfur-based ligands to promote more widespread adoption of sustainable ligands.

Energy Harvesting and Pd(II) Sorption Based on Organic-Inorganic Hybrid Perovskites.

Organic-inorganic hybrid perovskites are currently an active research topic in the field of energy and next-generation electronics. Their selectable organic and inorganic components provide infinite possibilities for designing functional materials with multiple applications. Herein, we present a new one-dimensional BaNiO3-like organic-inorganic hybrid perovskite (thiazolidinium)CdBr3 (1), which displays a phase transition at 263 K and a switchable second harmonic generation (SHG) response. Intriguingly, 1 shows a pyroelectric coefficient pe of ∼0.6 μC·cm-2·K-1 and a piezoelectric output voltage of ∼2.0 V for our fabricated piezoelectric generation device, indicating its great potential for pyroelectric sensors, self-powered low-voltage electronic devices, and energy harvesters. Moreover, the presence of a specific thioether donor enables 1 to appropriately adsorb Pd(II) ions, which can be monitored by the corresponding change in phase transition behavior, SHG signal, and pyroelectric response. This work provides a new insight to develop new multifunctional materials, demonstrating the feasibility of utilizing organic-inorganic hybrid perovskites to realize future self-powered low-voltage devices and energy harvesters.

A Stable Coordination Polymer Based on Rod-Like Silver(I) Nodes with Contiguous Ag-S Bonding.

Silver(I)-based coordination polymers or metal-organic frameworks (MOFs) display useful antibacterial properties, whereby distinct materials with different bonding can afford control over the release of silver(I) ions. Such silver(I) materials are comprised of discrete secondary building units (SBUs), and typically formed with ligands possessing only soft or borderline donors. We postulated that a linker with four potential donor groups, comprising carboxylate and soft thioether donors, 2,5-bis (allylsulfanyl) benzene dicarboxylic acid (ASBDC), could be used to form stable, highly connected coordination polymers with silver(I). Here, we describe the synthesis of a new material, (Ag2(ASBDC)), which possesses a rod-like metal node-based 3D honeycomb structure, strongly π-stacked linkers, and steric bulk to protect the node. Due to the rod-like metal node and the blocking afforded by the ordered allyl groups, the material displays notable thermal and moisture stability. An interesting structural feature of (Ag2(ASBDC)) is contiguous Ag–S bonding, essentially a helical silver chalcogenide wire, which extends through the structure. These interesting structural features, coupled with the relative ease by which MOFs made with linear dicarboxylate linkers can be reticulated, suggests this may be a structure type worthy of further investigation.

Ruthenium (II) complexes bearing thioether‐appended α‐iminopyridine ligands: Arene precursors permit access to κ2‐N,N and κ3‐N,N,S complexes

Herein we report the preparation of a series of Ru(II) complexes featuring α‐iminopyridine ligands bearing thioether functionality (NNSR, where R = Me, CH2Ph, Ph). Metallation using [(p‐cymene)RuCl]2 permits access to Ru complexes with a κ2‐N,N donor set in which the thioether moiety remains uncoordinated. In the presence of a strong field ligand such as acetonitrile or triphenylphosphine, the p‐cymene moiety is displaced, and the ligand adopts a κ3‐N,N,S binding mode. These complexes are characterized using a combination of solution and solid state methods, including the crystal structure of [(NNSMe)Ru (NCMe)2Cl]Cl. The κ2‐N,N‐Ru(II) complexes are shown to serve as efficient precatalysts for the oxidation of sec‐phenethyl alcohol at modest loadings (alcohol: Ru = 20:1), using a variety of external oxidants and solvents. The complex bearing an S‐Ph donor was found to be the most active oxidation catalyst of those surveyed, suggesting that the thioether donor plays an active role in the catalytic cycle.

Made in Water: A Stable Microporous Cu(I)-carboxylate Framework (CityU-7) for CO2, Water, and Iodine Uptake.

Using water as the sole solvent, the bifunctional molecule tetrakis(methylthio)-1,4-benzenedicarboxylic acid (TMBD) was reacted with Cu(CH3CN)4BF4 to form a robust microporous metal-organic framework (MOF, CityU-7) featuring Cu(I) ions being simultaneously bonded to the carboxyl and thioether donors. The MOF solid is stable in air and can be easily activated by heating, without the need for treatment with organic solvents. The subnanoscopic pores (ca. 0.6 nm) of the host net allow for uptake of CO2 and H2O but exhibit lesser sorption for N2 at 77 K. The microporous net can also be penetrated by I2 molecules.

Synthesis and crystallographic characterization of a mononuclear cobalt(III) complex possessing both thiol-ate and thio-ether donors: reactivity of an thiol-ate-bridged penta-nuclear Co2Ag3 complex with iodo-methane.

Treatment of an S-bridged penta-nuclear AgI3CoIII2 complex, [Ag3{Co(L)}2]3+ [L3- = N(CH2NHCH2CH2S-)3], in which two tris-(thiol-ate)-type mononuclear CoIII units ([Co(L)]) are bridged by three AgI ions through S atoms, with iodo-methane (CH3I) gave a new CoIII mononuclear complex, [Co(LMe2)]2+ [LMe2- = N(CH2NHCH2CH2S-)(CH2NHCH2CH2SCH3)2], systematic name: {2-[(bis{[2-(methylsulfanyl)ethyl]aminomethyl}aminomethyl)amino]ethanethiolato}cobalt(III) bis(hexafluoridophosphate). This cationic complex was crystallized with PF6- anions to form the title compound, [Co(LMe2)](PF6)2. In the [Co(LMe2)]2+ cation, two of three thiol-ate groups in [Co(L)] are methyl-ated while one thiol-ate group remains unreacted. Although a total of eight stereoisomers are possible for [Co(LMe2)]2+, only a pair of enanti-omers {Λ RR - and Δ SS -[Co(LMe2)]2+} are selectively formed. In the crystal, the complex cations and the PF-6- anions are connected through weak N-H⋯F, C-H⋯F and C-H⋯S hydrogen bonds into a three-dimensional structure. Two F atoms in one PF6 anion are disordered over two sets of sites with refined occupancies of 0.61 (4) and 0.39 (4) and two F atoms in the other PF6- anion are disordered over two sets of sites with occupancies of 0.5.

Emissive Ruthenium–Bisdiimine Complexes with Chelated Thioether Donors

AbstractThe photophysical properties of ruthenium(II) complexes of bidentate 2‐[(alkylthio)methyl]pyridine (N,S) ligands have been systematically investigated. The co‐ligands in the heteroleptic complexes were diimines (N,N ligands, e.g., bpy, phen) or tripodal tetradentate tris(2‐pyridylmethyl)amine (tpa). Their X‐ray structures revealed little variation in the Ru–S (2.31–2.33 Å) and Ru–N (2.06–2.11 Å) bond lengths. Despite this, considerable variation can be observed in the electrochemistry and spectroscopy measurements. The presence of the thioether sulfur donor results in a shift to a more positive potential of the Ru2+/Ru3+ process, and the absorption maxima are consequently blueshifted in [Ru(N,N)2(N,S)]2+ complexes compared with the [Ru(N,N)3]2+ analogues. The [Ru(N,N)2(N,S)]2+ complexes display strong room‐temperature emission from 3MLCT states, governed by the N,N donors. This is corroborated by low‐temperature steady‐state emission studies, which revealed typical 3MLCT emission profiles and excited‐state lifetimes of around 5–10 µs.

First-row transition metal complexes of ENENES ligands: the ability of the thioether donor to impact the coordination chemistry.

The reactions of two variants of ENENES ligands, E(CH2)2NH(CH)2SR, where E = 4-morpholinyl, R = Ph (), Bn () with MCl2 (M = Mn, Fe, Co, Ni and Cu) in coordinating solvents (MeCN, EtOH) affords isolable complexes, whose magnetic susceptibility measurements suggest paramagnetism and a high-spin formulation. X-Ray diffraction studies of available crystals show that the ligand coordinates to the metal in either a bidentate κ(2)[N,N'] or tridentate κ(3)[N,N',S] fashion, depending on the nature of ligand and/or identity of the metal atom. In the case of a less basic SPh moiety, a bidentate coordination mode was identified for harder metals (Mn, Fe), whereas a tridentate coordination mode was identified in the case of a more basic SBn moiety with softer metals (Ni, Cu). In the intermediate case of Co, ligands and coordinate via κ(2)[N,N'] and κ(3)[N,N',S] coordination modes, which can be conveniently predicted by DFT calculations. For the softest metal (Cu), ligand coordinates in a κ(3)[N,N',S] fashion.

A N3S(thioether)-ligated Cu(II)-superoxo with enhanced reactivity.

Previous efforts to synthesize a cupric superoxide complex possessing a thioether donor have resulted in the formation of an end-on trans-peroxo-dicopper(II) species, [{(Ligand)Cu(II)}2(μ-1,2-O2(2-))](2+). Redesign/modification of previous N3S tetradentate ligands has now allowed for the stabilization of the monomeric, superoxide product possessing a S(thioether) ligation, [((DMA)N3S)Cu(II)(O2(•-))](+) (2(S)), as characterized by UV-vis and resonance Raman spectroscopies. This complex mimics the putative Cu(II)(O2(•-)) active species of the copper monooxygenase PHM and exhibits enhanced reactivity toward both O-H and C-H substrates in comparison to close analogues [(L)Cu(II)(O2(•-))](+), where L contains only nitrogen donor atoms. Also, comparisons of [(L)Cu(II/I)](n+) compound reduction potentials (L = various N4 vs (DMA)N3S ligands) provide evidence that (DMA)N3S is a weaker donor to copper ion than is found for any N4 ligand-complex.

Introducing Potential Hemilability into “Click” Triazoles and Triazolylidenes: Synthesis and Characterization of d6‐Metal Complexes and Oxidation Catalysis

AbstractHemilabile ligands are known to impart remarkable properties to their metal complexes. Herein, we present arene half‐sandwich complexes of RuII, OsII, and IrIII with “click”‐derived 1,2,3‐triazole (L1) and 1,2,3‐triazol‐5‐ylidene (L2) ligands containing a potentially hemilabile thioether donor. Structural elucidation of the complexes revealed localization of double bonds within the triazole in L1 and a delocalized situation within the triazolylidene ring of L2. For complexes with L1, unusual coordination occurs through the less basic nitrogen “N2” of the 1,2,3‐triazole. All complexes were applied for the catalytic oxidation of benzyl alcohol to benzaldehyde using N‐methylmorpholine N‐oxide as sacrificial oxidant. Furthermore, oxidation of diphenylmethanol to benzophenone was also achieved by using low catalyst loadings in very good yields. These are rare examples of OsII–triazole, as well as of OsII–triazolylidene complexes with “click”‐derived ligands.

Ruthenium Bis-diimine Complexes with a Chelating Thioether Ligand: Delineating 1,10-Phenanthrolinyl and 2,2′-Bipyridyl Ligand Substituent Effects

Despite the high π-acidity of thioether donors, ruthenium(II) complexes with a bidentate 1,2-bis(phenylthio)ethane (dpte) ligand and two chelating diimine ligands (i.e., Ru(diimine)2(dpte)(2+)) exhibit room-temperature fluid solution emission originating from a lowest MLCT excited state (diimine = 2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine 4,4'-di-tert-butyl-2,2'-bipyridine, 1,10-phenanthroline, 5-methyl-1,10-phenanthroline, 5-chloro-1,10-phenanthroline, 5-bromo-1,10-phenanthroline, 5-nitro-1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline, and 3,4,7,8-tetramethyl-1,10-phenanthroline). Crystal structures show that the complexes form 2 of the 12 possible conformational/configurational isomers, as well as nonstatistical distributions of geometric isomers; there also are short intramolecular π-π interactions between the diimine ligands and dpte phenyl groups. The photoinduced solvolysis product, [Ru(diimine)2(CH3CN)2](PF6)2, for one complex in acetonitrile also was characterized by single-crystal X-ray diffraction. Variations in the MLCT energies and Ru(III/II) redox couple, E°'(Ru(3+/2+)), can be understood in terms of the influence of the donor properties of the ligands on the mainly metal-based HOMO and mainly diimine ligand-based LUMO. E°'(Ru(3+/2+)) also is quantitatively described using a summative Hammett parameter (σT), as well as using Lever's electrochemical parameters (EL). Recommended parametrizations for substituted 2,2'-bipyridyl and 1,10-phenanthrolinyl ligands were derived from analysis of correlations of E°'(Ru(3+/2+)) for 99 homo- and heteroleptic ruthenium(II) tris-diimine complexes. This analysis reveals that variations in E°'(Ru(3+/2+)) due to substituents at the 4- and 4'-positions of bipyridyl ligands and 4- and 7-positions of phenanthrolinyl ligands are significantly more strongly correlated with σp(+) than either σm or σp. Substituents at the 5- and 6-positions of phenanthrolinyl ligands are best described by σm and have effects comparable to those of substituents at the 3- and 8-positions. Correlations of EL with σT for 1,10-phenanthrolinyl and 2,2'-bipyridyl ligands show similar results, except that σp and σp(+) are almost equally effective in describing the influence of substituents at the 4- and 4'-positions of bipyridyl ligands. MLCT energies and d(5)/d(6)-electron redox couples of the complexes with 5-substituted 1,10-phenanthroline exhibit correlations with values for other d(6)-electron metal complexes that can be rationalized in terms of the relative number of diimine ligands and substituents.

An Interwoven Metal‐Organic Framework Combining Mechanically Interlocked Linkers and Interpenetrated Networks

New dibenzo[24]crown-8 ether derivatives were prepared that contain appendages with thioether donors that can coordinate to a metal ion. These macrocycles were then combined with 1,2-bis(pyridinium) ethane axles to create two types of [2]rotaxane ligands; those with the four thioether donors on the crown ether and those with six donor groups, four from the crown ether and two more attached to the stoppering groups of the dumbbell. The crown ethers and both types of [2]rotaxane ligands were allowed to react with Ag(I) ions to form metal-organic rotaxane framework (MORF) style coordination polymers. The interlocked hexadentate ligand forms the first example of a new type of lattice containing interwoven frameworks resulting from both interpenetration of frameworks due to the presence of an interlocked ligand and more classical interpenetration of independent frameworks.

Copper Versus Thioether‐Centered Oxidation: Mechanistic Insights into the Non‐Innocent Redox Behavior of Tripodal Benzimidazolylaminothioether Ligands

A series of Cu(+) complexes with ligands that feature varying numbers of benzimidazole/thioether donors and methylene or ethylene linkers between the central nitrogen atom and the thioether sulfur atoms have been spectroscopically and electrochemically characterized. Cyclic voltammetry measurements indicated that the highest Cu(2+)/Cu(+) redox potentials correspond to sulfur-rich coordination environments, with values decreasing as the thioether donors are replaced by nitrogen-donating benzimidazoles. Both Cu(2+) and Cu(+) complexes were studied by DFT. Their electronic properties were determined by analyzing their frontier orbitals, relative energies, and the contributions to the orbitals involved in redox processes, which revealed that the HOMOs of the more sulfur-rich copper complexes, particularly those with methylene linkers (-N-CH2-S-), show significant aromatic thioether character. Thus, the theoretically predicted initial oxidation at the sulfur atom of the methylene-bridged ligands agrees with the experimentally determined oxidation waves in the voltammograms of the NS3- and N2S2-type ligands as being ligand-based, as opposed to the copper-based processes of the ethylene-bridged Cu(+) complexes. The electrochemical and theoretical results are consistent with our previously reported mechanistic proposal for Cu(2+)-promoted oxidative C-S bond cleavage, which in this work resulted in the isolation and complete characterization (including by X-ray crystallography) of the decomposition products of two ligands employed, further supporting the novel reactivity pathway invoked. The combined results raise the possibility that the reactions of copper-thioether complexes in chemical and biochemical systems occur with redox participation of the sulfur atom.

Copper(II) complexes of aliphatic tridentate amine/dithioether ligands – Synthesis and molecular structures

Three new tridentate ligands (1–3) featuring a central secondary amine linked by ethylene bridges to two thioether donor functions with S-methyl or S-benzyl substituents have been synthesized and reacted with copper(II) chloride or copper(II) nitrate. The resulting complexes of type [CuX2(L)] (L=amine-dithioether ligand) 6, 7, and 9 exhibit a square-pyramidal coordination geometry with the nitrogen and sulfur donor groups of the tridentate ligand occupying three of the basal binding sites at the metal ion. Two chloro (6 and 7) or a nitrato ligand (9) originating from the metal precursor salt complete the coordination sphere of the copper(II) ion. The apical donors are bonded with significantly longer bond distances compared to identical donors in the basal plane. The weakly bound apical chloro ligand of 6 can be abstracted with silver(I) nitrate effecting the formation of the dinuclear complex 10 featuring a nitrato ligand coordinated to two copper(II) centers in a bridging fashion. For all copper(II) complexes the observed Cu–S bond distances are very similar and not significantly influenced by alteration of the alkyl group at the thioether donor function.

Ruthenium and Rhodium Complexes of Thioether-Alkynylborates

The species ((C6F5)2BCH2SPh)2 reacts with PhC≡CLi to give the thioether-alkynylborate (C6F5)2BCH2SPh(C≡CPh)Li(THF)2 (1). Subsequent reaction with (Ph3P)3RuHCl, (Ph3P)3RhCl, and [(COD)Rh(μ-Cl)]2 gives (C6F5)2BCH2SPh(C≡CPh)RuH(PPh3)2 (2), (C6F5)2BCH2SPh(C≡CPh)Rh(PPh3)2 (4), and (C6F5)2BCH2SPh(C≡CPh)Rh(COD) (5), respectively, demonstrating a bidentate binding mode via the alkynyl and thioether donors of the borate. Subsequent reactions of 2 and 4 with H2 gave (C6F5)2BCH2SPh(CH2CH2Ph)RuH(PPh3)2 (3) and ((C6F5)2BCH2SPh(CHCHPh))Rh(PPh3)2 (6). In the former case, the borate remains bound to the metal via a π-interaction with the thioether-arene ring, while in the latter case, S and alkene binding is observed.

Coordination chemistry of copper proteins: How nature handles a toxic cargo for essential function

Biological copper is coordinated predominantly by just three ligand types: the side chains of histidine, cysteine, and methionine, with of course some exceptions. The arrangement of these components, however, is fascinating. The diversity provided by just these three ligands provides choices of nitrogen vs. sulfur, neutral vs. charged, hydrophilic vs. hydrophobic, susceptibility to oxidation, and degree of pH-sensitivity. In this review we examine how the total number of ligands, their spatial arrangement and solvent accessibility, the various combinations of imidazole, thiolate, and thioether donors, all work together to provide binding sites that either enable copper to carry out a function, or safely transport it in a way that prevents toxic reactivity. We separate copper proteins into two broad classes, those that utilize the metal as a cofactor, or those that traffic the metal. Enzymes and proteins that utilize copper as a cofactor use high affinity sites of high coordination numbers of 4–5 that prevent loss of the metal during redox cycling. Copper trafficking proteins, on the other hand, promote metal transfer either by having low affinity binding sites with moderate coordination number ~ 4, or by having lower coordinate binding sites of 2–3 ligands that bind with high affinity. Both strategies retain the metal but allow transfer under appropriate conditions. Analysis of studies from our own lab on model peptides, combined with those from other labs, raises an interesting hypothesis that various methionine/histidine/cysteine combinations provide organisms with dynamic, multifunctional domains on copper trafficking proteins that facilitate copper transfer under different extracellular, subcellular, and tissue-specific scenarios of pH, redox environment, and presence of other copper carriers or target proteins.

Convenient, Efficient Synthesis of Amide-Thioethers in Ionic Liquids

An improved method for the synthesis of carboxamide ligands containing thioether donor sites is described. This replaces the pyridine as the reaction medium used in the classical method by tetrabutylammonium bromide. The desired products, 1,4-bis[o-(R-2-carboxamidophenyl)]-1,4-dithiobutane, R = quinoline (1), furan (2), thiophene (3), pyridine (4), and pyrazine (5), were obtained in good yields and shorter reaction times.

Photoinduced electron transfer cyclizations of aryl-linked phthalimides

The photochemistry of arene-linked phthalimides incorporating the carboxylate or thioether donor group was investigated. Simple N-phthalimidophenyl alkanoates exclusively gave photoreduction (CO2H/H-exchange) products. In contrast, ω-phthalimido-meta-phenoxy carboxylates underwent photodecarboxylative cyclizations in yields of 6–48%. Likewise, catechol-linked derivatives furnished analogue cyclization products in 18–38% yield. Using the photodecarboxylation protocol, macrocyclic target compounds with ring sizes up to 17 could thus be realized. Two model phthalimides containing a thioether branch at the ortho-position of the arene-linker gave the analogue seven-membered cyclization products in yields of 28% and 35%, respectively.