Reversible 1,2-Addition of Water To Form a Nucleophilic Mn(I) Hydroxide Complex: A Thermodynamic and Reactivity Study

(^iPrPN^HP)­Mn­(CO)₂(OH) (<b>2</b>; ^iPrPN^HP = HN­{CH₂CH₂(PⁱPr₂)}₂) was formed from the reversible 1,2-addition of water to (^iPrPNP)­Mn­(CO)₂ (<b>1</b>; ^iPrPNP = the deprotonated, amide form of the ligand, ^–N­{CH₂­CH₂(PⁱPr₂)}₂). This reversible reaction was probed via variable-temperature NMR experiments, and the energetics of the 1,2-addition/elimination was found to be slightly exothermic (−0.8 kcal/mol). The corresponding manganese hydroxide was found to react with aldehydes, yielding the corresponding manganese carboxylate complexes (^iPrPN^HP)­Mn­(CO)₂(CO₂R), where R = H, methyl, phenyl. While no reaction between <b>1</b> and neat benzaldehyde was observed, in the presence of water, conversion to the corresponding manganese-bound benzoate with formation of H₂ was observed. The catalytic oxidation of benzaldehyde by water without additives was unsuccessful due to strong product inhibition, with the manganese benzoate formed under a variety of reaction conditions. Upon addition of base, a catalytic cycle for the conversion of aldehyde to carboxylate and hydrogen can be devised

Origins of the Regioselectivity in the Lutetium Triflate Catalyzed Ketalization of Acetone with Glycerol: A DFT Study

We describe DFT computations that address the regioselective preference toward the five-membered ring product 1,3-dioxolane (solketal) over the six-membered-ring product (1,3-dioxane) during Lu(OTf)₃-catalyzed ketalization of acetone with glycerol. When ketalization occurs via the internal (secondary) −OH group of glycerol, only solketal production should be possible due to the symmetry of the intermediates. Ketalization via the terminal −OH group of glycerol is predicted to occur in a different manner than the conventionally proposed ketalization mechanism. A constrained hemiketal intermediate is invoked to explain the selectivity for solketal formation

Conjugation of Amphiphilic Proteins to Hydrophobic Ligands in Organic Solvent

Protein–ligand conjugations are usually carried out in aqueous media in order to mimic the environment within which the conjugates will be used. In this work, we focus on the conjugation of amphiphilic variants of elastin-like polypeptide (ELP), short elastin (sEL), to poorly water-soluble compounds like OPPVs (<i>p</i>-phenylenevinylene oligomers), triarylamines, and polypyridine-metal complexes. These conjugations are problematic when carried out in aqueous phase because hydrophobic ligands tend to avoid exposure to water, which in turn causes the ligand to self-aggregate and/or interact noncovalently with hydrophobic regions of the amphiphile. Ultimately, this behavior leads to low conjugation efficiency and contamination with strong noncovalent “conjugates”. After exploring the solubility of sEL in various organic solvents, we have established an efficient conjugation methodology for obtaining covalent conjugates virtually free of contaminating noncovalent complexes. When conjugating carboxylated ligands to the amphiphile amines, we demonstrate that even when only one amine (the N-terminus) is present, its derivatization is 98% efficient. When conjugating amine moieties to the amphiphile carboxyls (a problematic configuration), protein multimerization is avoided, 98–100% of the protein is conjugated, and the unreacted ligand is recovered in pure form. Our syntheses occur in “one pot”, and our purification procedure is a simple workup utilizing a combination of water and organic solvent extractions. This conjugation methodology might provide a solution to problems arising from solubility mismatch of protein and ligand, and it is likely to be widely applied for modification of recombinant amphiphiles used for drug delivery (PEG-antibodies, polymer-enzymes, food proteins), cell adhesion (collagen, hydrophobins), synthesis of nanostructures (peptides), and engineering of biocompatible optoelectronics (biological polymers), to cite a few