Syntheses and Structures of Arenethiolato Cobalt(II) Complexes Containing Acylamino Groups: Steric Effects of Bulky Ligands on Coordination and Geometry.

Bulky thiolato ligands have been developed for creating biomimetic model complexes of active sites in metalloenzymes. Herein, we report a series of di-ortho-substituted arenethiolato ligands containing bulky acylamino groups (RCONH; R = t-Bu-, (4-t-BuC6H4)3C-,{3,5-(Me2CH)2C6H3}3C-, and {3,5-(Me3Si)2C6H3}3C-) that were developed for biomimetics. Bulky hydrophobic substituents generate a hydrophobic space around the coordinating sulfur atom through the NHCO bond. This steric environment induces the formation of low-coordinate mononuclear thiolato Co(II) complexes. The well-positioned NHCO moieties in the hydrophobic space coordinate to the vacant sites of the cobalt center with different coordination modes, viz., the S,O-chelate of the carbonyl C═O or the S,N-chelate of the acylamido CON-. The solid (crystalline) and solution structures of the complexes were investigated in detail using single-crystal X-ray crystallography, 1H NMR, and absorption spectroscopic analyses. The spontaneous deprotonation of NHCO, which is commonly observed in metalloenzymes but requires a strong base in artificial systems, was simulated by forming a hydrophobic space in the ligand. This new ligand design strategy is advantageous for creating model complexes that have never been constructed artificially.

Stability Enhancement of a π-Stacked Helical Structure Using Substituents of an Amino Acid Side Chain: Helix Formation via a Nucleation-Elongation Mechanism.

Molecular design involving the incorporation of an α-amino acid residue into the side chain or main chain of a polymer is often used to stabilize artificial molecular architectures through intramolecular hydrogen bonding. However, this molecular design strategy rarely considers the importance of interactions between substituents at the α-position of amino acid moieties, as found in nature. Herein, we report the synthesis of a novel series of π-stacked helical poly(quinolylene-2,3-methylene) with amino acid derivatives bearing different substituents at the α-position. We found that the thermal stability of π-stacked helical poly(quinolylene-2,3-methylene) is significantly improved by packing the substituents in the empty spaces between the side chains. In particular, when a bulky cyclohexyl alanine derivative was used as the side chain, the π-stacked helical structure maintained its stability even in dimethylsulfoxide, a hydrogen bond competitor. The stabilization of the π-stacked structure by the amino acid substituents resulted in a unique polymerization behavior involving nucleation-elongation steps. In the case of derivatives with leucine and cyclohexyl alanine, which form stable π-stacked helical structures, metastable structures with entangled main chains were formed in the initial polymerization stage. These structures subsequently underwent an irreversible structural change to achieve a thermodynamically stable helical π-stacked conformation as a nucleus for subsequent polymerization. Thereafter, the polymerization reaction proceeded with the elongation of the π-stacked helical structure. Differences in the stability of these systems indicated that the amino acid substituents on the side chains determine the most thermodynamically stable π-stacked helical structure.

Conformational Switch of Arylopeptide: Helix-Helix Transition Based on Side Chain Solvation.

Controlling the structural transition between well-defined architectures found in living system is essential in polymer chemistry as well as material science. Herein, the reversible conformational switch of a non-natural polypeptide with an aromatic ring (2,6-naphthalene spacer) on its peptide backbone, referred to as an arylopeptide, between two distinct well-defined helical structures (extended 31 -helix and contracted 41 -helix) using side chain solvation is demonstrated. The folding selectivity of the arylopeptide and found that the affinity between the solvent and side chains is an essential factor for determining the global structure is investigated. A thermoresponsive arylopeptide bearing oligoether groups (─(CH2 CH2 O)9 CH3 )) on the side chain is designed, which exhibited unique lower critical solution temperature behavior and converted from the 31 to the 41 -helix depending on the temperature. Furthermore, the solvent affinity of the entire polymer by combining substituents (─(CH2 CH2 O)3 CH3 and ─C12 H25 ) with different properties on the side chains to achieve a spring-like expansion-contraction system that allows interconversion between 31 - and 41 -helices is adjusted.

Construction of Helically Stacked π-Electron Systems in Poly(quinolylene-2,3-methylene) Stabilized by Intramolecular Hydrogen Bonds.

π-Stacked polymers, which consist of layered π-electron systems in a polymer, can be expected to be used in molecular electronic devices. However, the construction of a stable π-stacked structure in a polymer is considerably challenging because it requires sophisticated designs and precise synthetic methods. Herein, we present a novel π-stacked architecture based on poly(quinolylene-2,3-methylene) bearing alanine derivatives as the side chain, obtained through the living cyclo-copolymerization of an o-allenylaryl isocyanide. In the resulting polymer, the neighboring quinoline rings of the main chain form a layered structure with π-π interactions, which is stabilized by intramolecular hydrogen bonds. The vicinal quinoline units form two independent helices and the whole molecule is a twisted-tape structure. This structure is established on the basis of UV/CD spectra, theoretical calculations, and atomic-force microscopy.

Folding control of a non-natural glycopeptide using saccharide-coded structural information for polypeptides.

We synthesized "glyco-arylopeptides", whose folding structure significantly changes depending on the kind of saccharide in their side chain. The saccharide moiety interacts with the main chain via hydrogen bonding, and the non-natural polypeptides form two well-defined architectures-(P)-31- and (M)-41-helices-depending on the length of the saccharide chains and even the configuration of a single stereo-genic center in the epimers.

Crystal-to-Crystal Isomerization via Drastic Intramolecular Ligand Exchange: Vapochromism of a Bis(arenethiolato)cobalt(II) Complex Containing Bulky Acylamino Groups.

Crystal-to-crystal transitions normally avoid drastic configurational changes that result in loss of crystallinity. A cobalt(II) complex, containing two unsymmetrically disubstituted arenethiolato ligands with bulky acylamino (Ar3CCONH, Ar = 4-t-BuC6H4) and t-BuCONH groups, showed crystal-to-crystal configurational isomerization accompanied by vapochromism. Recrystallization using THF/n-hexane afforded green crystals (isomer G) containing one n-hexane molecule per asymmetric unit. In contrast, blue crystals (isomer B), containing two toluene molecules per unit, were obtained using a toluene solution. Isomer G contained S,O-chelates involving Ar3CCO carbonyl groups, while isomer B contained chelates involving t-BuCO groups. Upon exposure to toluene vapor, crystal isomer G was gradually converted to crystal isomer B, maintaining its crystallinity despite the drastic intramolecular ligand exchange. Although the blue coloration was due to an unfavorable, distorted, and stretched chemical structure, formation of strong intermolecular NH···O═C hydrogen bond chains counteracted this disadvantage. Therefore, blue crystal formation as a whole was thermodynamically favorable. The release of n-hexane from the green crystals initiated the isomerization and resulted in tightly packed blue crystals. The tense conformation of the blue crystals was facilely relaxed by cleaving the hydrogen bond chains through grinding and resulted in a green powder that maintained the original coordination of isomer B, which reverted easily to blue crystals upon exposure to toluene vapor.

Living Cyclocopolymerization through Alternating Insertion of Isocyanide and Allene via Controlling the Reactivity of the Propagation Species: Detailed Mechanistic Investigation.

Living cyclocopolymerization through the alternating insertion of an isocyanide and allene into palladium-carbon bond was developed based on the controlling the reactivity of the propagation species using bidentate ligands. We revealed that the rate of the presented cyclocopolymerization was depended on the ligands of Pd-initiator. When the palladium-methyl complexes having appropriate cis-chelating ligand, such as 1,3-bis(diphenylphosphino)propane (dppp), were used as initiator, the cyclocopolymerization of bifunctional aryl isocyanides (1) that contain both isocyano and allenyl moieties polymerized to afford poly(quinolylene-2,3-methylene)s with controlled molecular weight and narrow molecular weight distributions. The resulting polymer was characterized by 1H and 13C NMR analyses, which clearly showed that the terminal moiety of the polymer formed well-defined organopalladium complex as the resting state for the polymerization, which could undergo further polymerization; not only cyclocopolymerization with 1 but also homopolymerization of simple aryl isocyanide. In the analysis of the cyclocopolymerization mechanism, we conclusively demonstrated that the insertion reaction of isocyanide is the rate-determination step in the cyclocopolymerization, which proceeds via a five-coordinate intermediate with a geometrical change. The cis-chelating ligand controls the site interchange reaction, which dominates the reactivity of propagation species.

Zigzag-Helix Transformation of Expanded Polyvaline Induced by Racemization.

Biological macromolecules are essentially homochiral. For example, proteins mostly consist of l-amino acids. What happens when a chiral molecule meets itself in a mirror? For expanded polyvaline, zigzag-helix transformation occurs. In this study, expanded polyvalines containing bis(pyridine)silver(I) moieties were synthesized and isolated as single crystals. The molecular structures were determined by X-ray analysis, which revealed that chiral expanded poly(l-valine) and poly(d-valine) form zigzag chains. However, racemic mixture of these molecules form left- and right-handed 41 helices that retain the original sequences. These secondary structures can be transformed by only flipping the C-terminal amide plane for each unit, which is reminiscent of the relationship between an α-helix and a ß-strand. Such expanded polypeptides can be built up into expanded protein, forming a tailor-made three-dimensional structure, which will lead to new functions.

Side-Chain-Driven Dual Structural System of Poly-Arylopeptide: Selective Helical Formation Derived from Aromatic Ring Flips on the Backbone.

A methodology for producing dual structural systems of macromolecules, which involves flipping the unsymmetrical aromatic rings on the main chain is presented. Previously, we reported a non-natural polypeptide containing an aromatic ring on the peptide backbone, called a poly "arylopeptide". Herein, we used 2,6-naphthalene rings as axially unsymmetrical spacers, which has two geometrical isomers, anti and syn, to create dual structural properties. The miniscule energy difference between the two geometrical isomers can be amplified by incorporating the 2,6-naphthylene units into the polypeptide backbone, which creates a thermodynamic driving force for the formation of two specific global structures (i.e., 31-helix or 41-helix) biased toward one side geometrical isomer depending on the side chain. Additionally, the 31-helix can be switched to the 41-helix upon addition of a small amount of additives, indicating a conformational conversion from an identical sequence. The developmental dual helical systems exploit basic molecular geometry and can serve as a design platform for synthetic polymers.

Crystal Structures of Expanded Poly(l-leucine) Isomers Containing Bis(pyridine)silver(I) Moieties: Precise Formation of Secondary Structure Depending on the Side Chain.

Precise construction of a three-dimensional molecular structure is key for functional macromolecules, such as enzymes or proteins. Previously, a new concept, "expanded poly(α-amino acid)s" containing rigid spacers, was proposed for strategic construction of chiral helices. Herein, expanded poly(l-leucine) isomers containing bis(pyridine)silver(I) moieties were synthesized, and their crystal structures were determined by X-ray analysis. Each expanded polypeptide forms a unique secondary structure, a left-handed 61 helix or zigzag chain (21 helix), precisely depending on the chemical structure of the side chain, that is, slight branching. Distinct conformations were indicated by two main areas in the Ramachandran plot. These results suggest that the appropriate selection of the amino acid sequence and rigid spacers will lead to a new expanded protein with a tailor-made three-dimensional structure and desired functions.

One-pot synthesis of imidazolinium salts via the ring opening of tetrahydrofuran.

A new one-pot synthesis of C2-hydroxypropyl-substituted imidazolinium salts via the ring opening of tetrahydrofuran (THF) with N,N'-disubstituted diamines has been developed. Preliminary studies of the reaction mechanism suggest the CO2-promoted oxidative ring opening of THF followed by Hg(ii)-mediated oxidation of an imidazolidine intermediate. These novel C2-substituted imidazolinium salts have shown to be active catalysts for the aza-Diels-Alder reactions.

Snapshot of Oxidation of Thiolate by Diiodine: Stabilization of Intermediate by NH···S Hydrogen Bonds.

Ordinary thiolate (RS-) reacts with diiodine (I2) to afford an intermediate sulfenyl iodide (RSI) by releasing I-; RSI is readily converted to disulfide (RSSR) by a disproportionation reaction. In the case of thiolate Ar1S- containing very bulky acylamino groups forming NH···S hydrogen bonds, the crystal of the intermediate, [Ar1S-I-I]-, was obtained under usual conditions, and the structure was determined by X-ray diffraction analysis. The results show that the intramolecular NH···S hydrogen bonds stabilized the intermediate [Ar1S-I-I]-, consistent with theoretical calculations.

Comparative studies on the contribution of NHS hydrogen bonds in tungsten and molybdenum benzenedithiolate complexes.

A series of monooxotungsten(iv) and dioxotungsten(vi) benzenedithiolates, (NEt4)2[WIVO(1,2-S2-3-RCONHC6H3)2] (1-W; R = CH3 (a), t-Bu (b), or CF3 (c)) and (NEt4)2[WVIO2(1,2-S2-3-RCONHC6H3)2] (2-W), were synthesized and compared with the corresponding molybdenum analogues. Single crystals of trans-1b-W were successfully obtained, and the crystal structure was determined by X-ray analysis although 1b-Mo could not be crystallized. The NHS hydrogen bonds shifted the potential of the W(iv/v) redox couple to more positive values, and the strength of the hydrogen bond and the positive shift value were strongly correlated. The hydrogen bonds in both 1-W and 2-W were weaker than those in the corresponding molybdenum analogues; however, the effect of the hydrogen bonds on the redox potential was greater in 1-W.

Correction: Significant differences of monooxotungsten(IV) and dioxotungsten(VI) benzenedithiolates containing two intramolecular NH···S hydrogen bonds from molybdenum analogues.

Correction for 'Significant differences of monooxotungsten(IV) and dioxotungsten(VI) benzenedithiolates containing two intramolecular NH···S hydrogen bonds from molybdenum analogues' by Taka-aki Okamura et al., Dalton Trans., 2015, 44, 18090-18100.

Significant differences of monooxotungsten(IV) and dioxotungsten(VI) benzenedithiolates containing two intramolecular NHS hydrogen bonds from molybdenum analogues.

A monooxotungsten(iv) benzenedithiolate complex containing two intramolecular NHS hydrogen bonds, (NEt4)2[W(IV)O(1,2-S2-3-t-BuNHCOC6H3)2] (1-W), was synthesized via a ligand-exchange reaction between a new starting complex, (NEt4)2[W(IV)O(SC6F5)4], and a partially deprotonated dithiol. When dithiol was used in solution, the oxo ligand was protonated and removed to afford (NEt4)2[W(IV)(1,2-S2-3-t-BuNHCOC6H3)3]. The trans isomer, trans-1-W, was crystallized, and the molecular structure was determined via X-ray analysis. Trans-1-W was gradually isomerized by heating it in solution and it eventually achieved an approximately 1 : 1 mixture of trans/cis isomers after 48 days. However, a slightly excess amount of trans isomer remained, so the isomerization rate was considerably slower than that of the molybdenum analogue. In the presence of NEt4BH4, deuteration of the NH protons was observed in acetonitrile-d3. The oxidation of both trans- and cis-1-W by Me3NO afforded the corresponding dioxotungsten(vi) complex, (NEt4)2[W(VI)O2(1,2-S2-3-t-BuNHCOC6H3)2] (2-W), as a single isomer. The contributions of the NHS hydrogen bonds to the bond distances, vibrational data, and electrochemical properties are described via comparisons with their molybdenum analogues. The results of this comparative study yielded insights into both tungsten and molybdenum enzymes.

Modeling of the hydrophobic microenvironment of water-soluble molybdoenzymes in an aqueous micellar solution.

A toluene-soluble molybdenum(vi) complex containing a bulky hydrophobic substituent, (Et4N)2[Mo(VI)O2{1,2-S2-3,6-(RCONH)2C6H2}2] (R = (4-(t)BuC6H4)3C), was dissolved in the hydrophobic core of a micelle in an aqueous medium and catalyzed the biomimetic reduction of an amine N-oxide by an NADH analog. The kinetic isotope effect of solvent water clearly indicates that water molecules are essential for catalysis and are involved in the rate-determining step.

Enantio- and diastereoselective asymmetric allylic alkylation catalyzed by a planar-chiral cyclopentadienyl ruthenium complex.

We report asymmetric allylic alkylation of allylic chloride with ß-diketones as the prochiral carbon nucleophiles using a planar-chiral Cp'Ru catalyst. The reaction proceeds under mild conditions; the resulting chiral products containing vicinal tertiary stereocenters are obtained with high regio-, diastereo-, and enantioselectivities. These chiral products can then be transformed into a chiral diol by controlling the four stereocentres.

Synthesis and structures of soluble magnesium and zinc carboxylates containing intramolecular NH···O hydrogen bonds in nonpolar solvents.

Readily soluble magnesium and zinc carboxylates [M(Ln)2(H2O)4] (MLn2) (M = Mg, Zn; L1 = O2C-2-Ar3CCONH-6-n-BuCONHC6H3; L2 = O2C-2-Ar3CCONHC6H4; Ar = 4-t-BuC6H4) containing intramolecular NH···O hydrogen bonds in nonpolar solvents were synthesized and their molecular structures were determined by X-ray analysis. The complexes were crystallized in the trans or cis configuration. The M­O bond distances were dependent on the mode of the hydrogen bonds. (1)H NMR spectral measurements revealed a fast trans­cis isomerization of MLn2 in CDCl3, which was converted into a unique fac-[M(Ln)3(H2O)3]− (fac-[MLn3]−) by the addition of equimolar [Ln]−. The theoretical calculations supported the existence of the facial configuration. The coordinated water molecules of MLn2 were detected by (1)H NMR spectroscopy and the acidity was estimated in the order of ML12 > ML22. Calcium afforded only the dinuclear complex, [Ca2(L1)2(H2O)5(1,4-dioxane)] (Ca2L14), which showed a low hydrolytic activity.

Efficient uptake of dimethyl sulfoxide by the desoxomolybdenum(IV) dithiolate complex containing bulky hydrophobic groups.

A desoxomolybdenum(IV) complex containing bulky hydrophobic groups and NH···S hydrogen bonds, (Et4N)[Mo(IV)(OSi(t)BuPh2)(1,2-S2-3,6-{(4-(t)BuC6H4)3CCONH}2C6H2)2], was synthesized. This complex promotes the oxygen-atom-transfer (OAT) reaction of DMSO by efficient uptake of the substrate into the active center. The clean OAT reaction of Me3NO is also achieved.

Regulation of the hydrolytic activity of Mg²âº-dependent phosphatase models by intramolecular NH···O hydrogen bonds.

Magnesium-dependent phosphatase models containing intramolecular NH···O hydrogen bonds were synthesized and structurally characterized by X-ray analysis. The Mg-O bond distances varied with the mode of the hydrogen bonds. (1)H NMR spectra in nonpolar solvents revealed that the acidity of the coordinated water molecule was regulated by the hydrogen bonds. Further, stoichiometric hydrolysis of phosphoric ester significantly depended on the hydrogen bonds. Zinc analogues showed similar but smaller dependencies, which suggest the indispensable role of Mg(2+) ion in the activation of the enzymes.