Mixed-Sandwich Cp*Cr Complexes Containing Poly(methimazolyl)borates (Cp* = C₅Me₅): Syntheses and Structural and Electrochemical Studies

Reaction of the scorpionate salts K­[HB­(mt)₃], Na­[H₂B­(mt)₂], and Li­[HB­(mt)₂(pz)] with [Cp*CrBr₂]₂ (<b>1</b>) gave the 15-electron Cr­(III) complexes [Cp*Cr­{κ³<i>-S</i>,<i>S′</i>,<i>S″</i>-HB­(mt)₃}]Br (<b>2</b>), [Cp*Cr­{κ²<i>-S</i>,<i>S′</i>-H₂B­(mt)₂}­Br] (<b>3</b>), and [Cp*Cr­{κ²<i>-S,S′</i>-HB­(mt)₂(pz)}­Br] (<b>4</b>) in moderate to high yields. These are the first examples of mixed-sandwich chromium­(III) complexes containing poly­(methimazolylborate) ligands. The tridentate coordination of the monoanionic ligands [H₂B­(mt)₂] in <b>3</b> and [HB­(mt)₂(pz)] in <b>4</b> can be effected by using a silver salt to remove the Br coligand, thus yielding the complexes [Cp*Cr­{κ³<i>-H</i>,<i>S</i>,<i>S′</i>-H₂B­(mt)₂}]­PF₆ (<b>6</b>) and [Cp*Cr­{κ³<i>-N</i>,<i>S</i>,<i>S′</i>-HB­(mt)₂(pz)}]­PF₆ (<b>7</b>). It was also found that, in the presence of acetonitrile, the reaction of <b>3</b> with AgPF₆ afforded [Cp*Cr­{κ²<i>-S</i>,<i>S′</i>-H₂B­(mt)₂}­(NCMe)]­PF₆ (<b>5</b>). The coordination geometries of all the complexes have been determined by X-ray diffraction analyses. Cyclic voltammetric studies of complexes <b>2</b>,<b> 4</b>, and <b>7</b> showed that the oxidation and reduction processes are chemically reversible and that the reduced and oxidized states of complexes <b>3</b>, <b>5</b>, and <b>6</b> are very short-lived

Mixed-Sandwich (Cp*/(HMB))Ru Complexes Containing Bis(methimazolyl)(pyrazolyl)borate (Cp* = η⁵-C₅Me₅, HMB = η⁶-C₆Me₆)

Reaction of the scorpionate salt Li­[HB­(mt)₂(pz)] (mt = <i>N</i>-methyl-2-mercaptoimidazol-1-yl, pz = pyrazolyl) with the organometallic complexes [Cp*RuOMe]₂ (Cp* = η⁵-C₅Me₅) (<b>1</b>) and [(HMB)­RuCl₂]₂ (HMB = η⁶-C₆Me₆) (<b>2</b>) gave the 18-electron Ru­(II) complexes [Cp*Ru­(κ³<i>-H,S,S′</i>)<i>-</i>{HB­(mt)₂(pz)}] (<b>3</b>) and [(HMB)­Ru­(κ³<i>-H,S,S′</i>)<i>-</i>{HB­(mt)₂(pz)}]­(<b>4B</b>)­PF₆ in moderate yields. In the absence of the PF₆^– anion, [(HMB)­Ru­(κ²-<i>S</i>,<i>S</i>′-{HB­(mt)₂(pz)})­(Cl)] [<b>4C</b>] was isolated as a coproduct with (<b>4B</b>)­Cl. These complexes are the first examples of organoruthenium­(II) complexes containing bis­(methimazolyl)­(pyrazolyl)­borate ligands. Isomers of <b>4B</b> were observed in solution, and the isomerization process was studied using variable-temperature ¹H NMR spectroscopy. The reactivity of <b>3</b> toward O₂ and CO was investigated, and in the process we isolated the first Ru­(IV) peroxo complex containing a poly­(methimazolyl)­borate ligand, [Cp*Ru­(κ²-<i>S</i>,<i>S</i>′-{HB­(mt)₂(pz)})­(η²-O₂)] (<b>5</b>), and a CO adduct, [Cp*Ru­(κ²-<i>S</i>,<i>S</i>′-{HB­(mt)₂(pz)})­(CO)] (<b>6</b>), respectively. The oxidation process was reversible, but treatment of <b>5</b> with CO converted it irreversibly to <b>6</b>. All the new compounds were fully characterized, including by X-ray diffraction analyses. Cyclic voltammetric studies were also conducted for complexes <b>3</b>, <b>5</b>, and <b>6</b>

Mixed-Sandwich (Cp*/(HMB))Ru Complexes Containing Bis(methimazolyl)(pyrazolyl)borate (Cp* = η⁵-C₅Me₅, HMB = η⁶-C₆Me₆)

Reaction of the scorpionate salt Li­[HB­(mt)₂(pz)] (mt = <i>N</i>-methyl-2-mercaptoimidazol-1-yl, pz = pyrazolyl) with the organometallic complexes [Cp*RuOMe]₂ (Cp* = η⁵-C₅Me₅) (<b>1</b>) and [(HMB)­RuCl₂]₂ (HMB = η⁶-C₆Me₆) (<b>2</b>) gave the 18-electron Ru­(II) complexes [Cp*Ru­(κ³<i>-H,S,S′</i>)<i>-</i>{HB­(mt)₂(pz)}] (<b>3</b>) and [(HMB)­Ru­(κ³<i>-H,S,S′</i>)<i>-</i>{HB­(mt)₂(pz)}]­(<b>4B</b>)­PF₆ in moderate yields. In the absence of the PF₆^– anion, [(HMB)­Ru­(κ²-<i>S</i>,<i>S</i>′-{HB­(mt)₂(pz)})­(Cl)] [<b>4C</b>] was isolated as a coproduct with (<b>4B</b>)­Cl. These complexes are the first examples of organoruthenium­(II) complexes containing bis­(methimazolyl)­(pyrazolyl)­borate ligands. Isomers of <b>4B</b> were observed in solution, and the isomerization process was studied using variable-temperature ¹H NMR spectroscopy. The reactivity of <b>3</b> toward O₂ and CO was investigated, and in the process we isolated the first Ru­(IV) peroxo complex containing a poly­(methimazolyl)­borate ligand, [Cp*Ru­(κ²-<i>S</i>,<i>S</i>′-{HB­(mt)₂(pz)})­(η²-O₂)] (<b>5</b>), and a CO adduct, [Cp*Ru­(κ²-<i>S</i>,<i>S</i>′-{HB­(mt)₂(pz)})­(CO)] (<b>6</b>), respectively. The oxidation process was reversible, but treatment of <b>5</b> with CO converted it irreversibly to <b>6</b>. All the new compounds were fully characterized, including by X-ray diffraction analyses. Cyclic voltammetric studies were also conducted for complexes <b>3</b>, <b>5</b>, and <b>6</b>

Mixed-Sandwich Cp*Cr Complexes Containing Poly(methimazolyl)borates (Cp* = C₅Me₅): Syntheses and Structural and Electrochemical Studies

Reaction of the scorpionate salts K­[HB­(mt)₃], Na­[H₂B­(mt)₂], and Li­[HB­(mt)₂(pz)] with [Cp*CrBr₂]₂ (<b>1</b>) gave the 15-electron Cr­(III) complexes [Cp*Cr­{κ³<i>-S</i>,<i>S′</i>,<i>S″</i>-HB­(mt)₃}]Br (<b>2</b>), [Cp*Cr­{κ²<i>-S</i>,<i>S′</i>-H₂B­(mt)₂}­Br] (<b>3</b>), and [Cp*Cr­{κ²<i>-S,S′</i>-HB­(mt)₂(pz)}­Br] (<b>4</b>) in moderate to high yields. These are the first examples of mixed-sandwich chromium­(III) complexes containing poly­(methimazolylborate) ligands. The tridentate coordination of the monoanionic ligands [H₂B­(mt)₂] in <b>3</b> and [HB­(mt)₂(pz)] in <b>4</b> can be effected by using a silver salt to remove the Br coligand, thus yielding the complexes [Cp*Cr­{κ³<i>-H</i>,<i>S</i>,<i>S′</i>-H₂B­(mt)₂}]­PF₆ (<b>6</b>) and [Cp*Cr­{κ³<i>-N</i>,<i>S</i>,<i>S′</i>-HB­(mt)₂(pz)}]­PF₆ (<b>7</b>). It was also found that, in the presence of acetonitrile, the reaction of <b>3</b> with AgPF₆ afforded [Cp*Cr­{κ²<i>-S</i>,<i>S′</i>-H₂B­(mt)₂}­(NCMe)]­PF₆ (<b>5</b>). The coordination geometries of all the complexes have been determined by X-ray diffraction analyses. Cyclic voltammetric studies of complexes <b>2</b>,<b> 4</b>, and <b>7</b> showed that the oxidation and reduction processes are chemically reversible and that the reduced and oxidized states of complexes <b>3</b>, <b>5</b>, and <b>6</b> are very short-lived

“Tag and Modify” Protein Conjugation with Dynamic Covalent Chemistry

The development of small protein tags that exhibit bioorthogonality, bond stability, and reversibility, as well as biocompatibility, holds great promise for applications in cellular environments enabling controlled drug delivery or for the construction of dynamic protein complexes in biological environments. Herein, we report the first application of dynamic covalent chemistry both for purification and for reversible assembly of protein conjugates using interactions of boronic acid with diols and salicylhydroxamates. Incorporation of the boronic acid (BA) tag was performed in a site-selective fashion by applying disulfide rebridging strategy. As an example, a model protein enzyme (lysozyme) was modified with the BA tag and purified using carbohydrate-based column chromatography. Subsequent dynamic covalent “click-like” bioconjugation with a salicylhydroxamate modified fluorescent dye (BODIPY FL) was accomplished while retaining its original enzymatic activity

pH Responsive Janus-like Supramolecular Fusion Proteins for Functional Protein Delivery

A facile, noncovalent solid-phase immobilization platform is described to assemble Janus-like supramolecular fusion proteins that are responsive to external stimuli. A chemically postmodified transporter protein, DHSA, is fused with (imino)­biotinylated cargo proteins via an avidin adaptor with a high degree of spatial control. Notably, the derived heterofusion proteins are able to cross cellular membranes, dissociate at acidic pH due to the iminobiotin linker and preserve the enzymatic activity of the cargo proteins β-galactosidase and the enzymatic subunit of <i>Clostridium botulinum</i> C2 toxin. The mix-and-match strategy described herein opens unique opportunities to access macromolecular architectures of high structural definition and biological activity, thus complementing protein ligation and recombinant protein expression techniques

Dendronized Albumin Core–Shell Transporters with High Drug Loading Capacity

We describe the synthesis of a core–shell biohybrid consisting of a human serum albumin (HSA) core that serves as a reservoir for lipophilic molecules and a cationized shell region consisting of <b>ethynyl-G2.0</b>-<b>PAMAM</b> or <b>ethynyl-G3.0</b>-<b>PAMAM</b> dendrons. The binding capacity of lipophilic guests was quantified applying electron paramagnetic resonance (EPR) spectroscopy, and five to six out of seven pockets were still available compared with HSA. The attachment of <b>ethynyl-G2.0</b>-<b>PAMAM</b> dendrons to HSA yielded a nontoxic core–shell macromolecule that was clearly uptaken by A549 human epithelial cells due to the presence of the dendritic PAMAM shell. Significantly higher loading of doxorubicin was observed for dendronized <b>G2-DHSA</b> compared with the native protein due to the availability of binding pockets of the HSA core, and interaction with the dendritic shell. Dendronized <b>G2-DHSA</b>-doxorubicin displayed significant cytotoxicity resulting from high drug loading and high stability under different conditions, thus demonstrating its great potential as a transporter for drug molecules

Chemoselective Dual Labeling of Native and Recombinant Proteins

The attachment of two different functionalities in a site-selective fashion represents a great challenge in protein chemistry. We report site specific dual functionalizations of peptides and proteins capitalizing on reactivity differences of cysteines in their free (thiol) and protected, oxidized (disulfide) forms. The dual functionalization of interleukin 2 and EYFP proceeded with no loss of bioactivity in a stepwise fashion applying maleimide and disulfide rebridging allyl-sulfone groups. In order to ensure broader applicability of the functionalization strategy, a novel, short peptide sequence that introduces a disulfide bridge was designed and site-selective dual labeling in the presence of biogenic groups was successfully demonstrated