Disubstituted Bis Research Articles

Selective Pathway toward Heteroleptic Spin-Crossover Iron(II) Complexes with Pyridine-Based N-Donor Ligands

A new synthetic pathway is devised to selectively produce previously elusive heteroleptic iron(II) complexes of terpyridine and N,N'-disubstituted bis(pyrazol-3-yl)pyridines that stabilize the opposite spin states of the metal ion. Such a combination of the ligands in a series of the heteroleptic complexes induces the spin-crossover (SCO) not experienced by the homoleptic complexes of these ligands or shifts it to lower/higher temperatures respective to the SCO-active homoleptic complex. The midpoint temperatures of the resulting SCO span from ca. 200 K to the ambient temperature and beyond the highest temperature accessible by NMR spectroscopy and SQUID magnetometry. The proposed "one-pot" approach is applicable to other N-donor ligands to selectively produce heteroleptic complexes─including those inaccessible by alternative synthetic pathways─with highly tunable SCO behaviors for practical applications in sensing, switching, and multifunctional devices.

Room-Temperature Spin Crossover in a Solution of Iron(II) Complexes with N,N'-Disubstituted Bis(pyrazol-3-yl)pyridines.

Here, we report a combined study of the effects of two chemical modifications to an N,N′-disubstituted bis(pyrazol-3-yl)pyridine (3-bpp) and of different solvents on the spin-crossover (SCO) behavior in otherwise high-spin iron(II) complexes by solution NMR spectroscopy. The observed stabilization of the low-spin state by electron-withdrawing substituents in the two positions of the ligand that induce opposite electronic effects in SCO–active iron(II) complexes of isomeric bis(pyrazol-1-yl)pyridines (1-bpp) was previously hidden by NH functionalities in 3-bpp precluding the molecular design of SCO compounds with this family of ligands. With the recent SCO-assisting substituent design, the uncovered trends converged toward the first iron(II) complex of N,N′-disubstituted 3-bpp to undergo an almost complete SCO centered at room temperature in a less polar solvent of a high hydrogen-bond acceptor ability.

Derivatives of Bis(trifluoromethyl)biphenyl and Various Donor Noieties Exhibiting Dual State Emission

A series of bis(trifluoromethyl)biphenyl derivatives bearing carbazole, dimethylacridan, and phenothiazine donor moieties were designed and synthesized via Ullman coupling reaction. The compounds were found to be capable of forming molecular glasses with glass transition temperatures ranging from 152 °C to 244 °C. Significant dual-state emission was revealed for the synthesized compounds. Radiative decay of singlet and triplet states emerged from restricted molecular motion in solid state. The phenothiazinyl-substituted bis(trifluoromethyl)biphenyl derivative induces particular interest, as it exhibits room-temperature phosphorescence. This makes it promising for oxygen sensing applications. The theoretical work revealed that carbazolyl disubstituted bis(trifluoromethyl)biphenyl has the largest deviation of the planes of donor and acceptor fragments from 90°, which leads to larger overlap of electron density in the ground and excited states and larger oscillator strength. The calculated values of dipole moment and charge transfer during excitation were found to be the lowest for phenothiazinyl disubstituted bis(trifluoromethyl)biphenyl. This result explains the experimental fact that the solvent polarity has the least effect on the fluorescent spectrum of this compound.

Spin-Crossover in Iron(II) Complexes of N,N′-Disubstituted 2,6-Bis(Pyrazol-3-yl)Pyridines: An Effect of a Distal Substituent in the 2,6-Dibromophenyl Group

A series of new bis(pyrazol-3-yl)pyridines (LR) N,N′-disubstituted by 4-functionalized 2,6-dibromophenyl groups have been synthesized to study the effect of a distal substituent on the spin-crossover (SCO) behaviour of the iron(II) complexes [Fe(LR)2](ClO4)2 by variable-temperature magnetometry, NMR spectroscopy, and X-ray diffraction. The SCO-assisting tendency of the substituents with different electronic and steric properties (i.e., the bromine atom and the methyl group) in the para-position of the 2,6-dibromophenyl group is discussed. Together with earlier reported SCO-active iron(II) complexes with N,N′-disubstituted bis(pyrazol-3-yl)pyridines, these new complexes open the way for this family of SCO compounds to emerge as an effective ‘tool’ in revealing structure–function relations, a prerequisite for successful molecular design of switchable materials for future breakthrough applications in sensing, switching, and memory devices.

Aromatic polyesters derived from 5,5′-disubstituted bis(m-phenylene) crown ethers

A new monomer of the AB type, 5-carboxy-1,3-phenylene-5′-hydroxy-1′,3′-phenylene-32-crown-10 (5), was synthesized. Direct polymerizations of bis(5-hydroxy-1,3-phenylene)-32-crown-10 (13), an AA diphenolic macrocyclic monomer, with BB diacid monomer bis(5-carboxy-1,3-phenylene)-26-crown-8 (14) and its larger analog bis(5-carboxy-1,3-phenylene)-32-crown-10 (16) were accomplished via the Higashi method. The resultant polyesters 15 and 17, which both contain two macrocycles per repeat unit, were soluble in common organic solvents such as chloroform and tetrahydrofuran, amorphous in nature and possessed high thermal stability (5% weight loss > 370 °C in air). Main chain poly(ester crown ether)s 18 and 19 based on bis(5-carboxy-1,3-phenylene)-32-crown-10 (16), and hydroquinone (HQ) and biphenol (BP), respectively, were synthesized; these two polyesters also possess high thermal stability (5% weight loss > 386 °C in air) and are amorphous. These polymacrocycles are suitable polytopic hosts for complexation with 4,4′-bipyridinium derivatives, as demonstrated by the binding of paraquat diol (21a) by polyester 20 with Ka = 2.0 (±0.7) x 102 M−1 (23 °C, 4:6 w:w CD3CN:CDCl3). Threading of the cyclic units in these polyesters by linear polymers such as polystyrene and PMMA leads to compatiblized blends via polypseudorotaxane formation; this methodology represents a new approach to compatibilization.

Synthesis and characterization of metal (M = Al or Ga) 2-phosphino(phenolate/benzenethiolate) complexes and their electrochemical behavior in the presence of CO2

A series of Group 13 complexes MLX2 (M = Al or Ga, L = SC6H4-2-PtBu2 or OC6H4-2-PtBu2, X = Me or C6F5) have been synthesized and characterized by multinuclear NMR spectroscopy and single crystal X-ray diffraction. Reactions of Me3Al or Me3Ga with an equivalent of either 2-tBu2P(C6H4)OH (1) or 2-tBu2P(C6H4)SH (5) resulted in the formation of four new (2,3,6, and 7), 4-coordinate dimethyl chelate (S,P or O,P) complexes via methane elimination. The dimethyl gallium complexes (3 and 7) underwent a further reaction with excess B(C6F5)3, and through ligand exchange (methyl/pentafluorophenyl), resulted in the disubstituted bis(pentafluorophenyl) analogs (4 and 8). Cyclic voltammetry (CV) experiments for all compounds in the presence of and the absence of (1–8) CO2 were performed. For compounds showing cathodic reduction waves under CO2 (2,3,4, and 6), bulk electrolysis experiments were performed. Electrochemical studies indicate that, for several compounds, a transient CO2 adduct is formed which undergoes a one-electron, irreversible (or partially irreversible) reduction to form an unstable radical anion.

A Single-Site Iron(III)-Salan Catalyst for Converting COS to Sulfur-Containing Polymers.

An iron(III) complex of tetradentate N,N′-disubstituted bis(aminophenoxide) (designated as salan, a saturated version of the corresponding salen ligand) with a sterically hindered organic base anchored on the ligand framework, can selectively mediate the conversion of carbonyl sulfide to sulfur-containing polymers by the copolymerization with epoxides. This single-site catalyst exhibits broad substrate scope, and the resultant copolymers have completely alternating structures. In addition, this catalyst is efficient in producing diblock copolymers, suggesting a living polymerization nature.

Identification of differential anti-neoplastic activity of copper bis(thiosemicarbazones) that is mediated by intracellular reactive oxygen species generation and lysosomal membrane permeabilization

Bis(thiosemicarbazones) and their copper (Cu) complexes possess unique anti-neoplastic properties. However, their mechanism of action remains unclear. We examined the structure–activity relationships of twelve bis(thiosemicarbazones) to elucidate factors regarding their anti-cancer efficacy. Importantly, the alkyl substitutions at the diimine position of the ligand backbone resulted in two distinct groups, namely, unsubstituted/monosubstituted and disubstituted bis(thiosemicarbazones). This alkyl substitution pattern governed their: (1) CuII/I redox potentials; (2) ability to induce cellular 64Cu release; (3) lipophilicity; and (4) anti-proliferative activity. The potent anti-cancer Cu complex of the unsubstituted bis(thiosemicarbazone) analog, glyoxal bis(4-methyl-3-thiosemicarbazone) (GTSM), generated intracellular reactive oxygen species (ROS), which was attenuated by Cu sequestration by a non-toxic Cu chelator, tetrathiomolybdate, and the anti-oxidant, N-acetyl-l-cysteine. Fluorescence microscopy suggested that the anti-cancer activity of Cu(GTSM) was due, in part, to lysosomal membrane permeabilization (LMP). For the first time, this investigation highlights the role of ROS and LMP in the anti-cancer activity of bis(thiosemicarbazones).

A Novel and Highly Regioselective Synthesis of New Carbamoylcarboxylic Acids from Dianhydrides

A regioselective synthesis has been developed for the preparation of a series of N,N′-disubstituted 4,4′-carbonylbis(carbamoylbenzoic) acids and N,N′-disubstituted bis(carbamoyl) terephthalic acids by treatment of 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (1) and 1,2,4,5-benzenetetracarboxylic dianhydride (2) with arylalkyl primary amines (A-N). The carbamoylcarboxylic acid derivatives were synthesized with good yield and high purity. The specific reaction conditions were established to obtain carbamoyl and carboxylic acid functionalities over the thermodynamically most favored imide group. Products derived from both anhydrides 1 and 2 were isolated as pure regioisomeric compounds under innovative experimental conditions. The chemo- and regioselectivity of products derived from dianhydrides were determined by NMR spectroscopy and confirmed by density functional theory (DFT). All products were characterized by NMR, FTIR, and MS.

Facile syntheses of disubstituted bis(vinylquinolinium)benzene derivatives as G-quadruplex DNA binders

A series of disubstituted bis(vinylquinolinium)benzene derivatives were designed, which were prepared through a facile three-component one-pot reaction in good yield. FRET results showed that 1,3-disubstituted benzene derivatives had much stronger stabilization effect on G-quadruplex DNA than that of 1,4-disubstituted benzene derivatives. The introduction of substituted amine side chain at quinolinium obviously increased the binding affinity of compounds to G-quadruplex DNA. It was also found that 1,3-disubstituted benzene derivatives and 1,4-disubstituted benzene derivatives had different effects on the conformation of G-quadruplex DNA by CD spectroscopy analysis. The differences for the interactions of these two classes of compounds with G-quadruplex were further studied and elaborated through molecular modeling experiments.

One‐Pot Synthesis and Characterization of Some New Types of 5,5′‐Disubstituted Bis(imidazolidine‐2,4‐diones)

The synthesis and structural elucidation of some novel 5,5′‐disubstituted spiro and nonspiro‐bis‐hydantoins are reported. The Bucherer Burge's method has been modified for the preparation of some 5,5′‐substituted bis(imidazolidine‐2,4‐dione) derivatives starting with diketones (1–5) and dialdehydes (6, 7). In some cases, diastereoisomeric mixtures of compounds were obtained. The resulting bis‐hydantoins (8–11, 13, 14) have not to our knowledge been previously reported in the literature.

Asymmetric, regio‐ and stereo‐selective alternating copolymerization of CO2 and propylene oxide catalyzed by chiral chromium Salan complexes

AbstractChiral chromium complexes of tetradentate N,N′‐disubstituted bis(aminophenoxide) (designated as Salan, a saturated version of Schiff‐base Salen ligand) in conjunction with an ionic quaternary ammonium salt can efficiently catalyze the copolymerization of CO2 with racemic propylene oxide (rac‐PO) at mild conditions to selectively afford completely alternating poly(propylene carbonate) (PPC) with ∼ 95% head‐to‐tail linkages and moderate enantioselectivity. These new catalyst systems predominantly exceed the previously much‐studied SalenCr(III) systems in catalytic activity, polymer enantioselectivity, and stereochemistry control. The chiral diamine backbone, sterically hindered substitute groups on the aromatic rings, and the presence of sp3‐hydridized amino donors and its N,N′‐disubstituted groups in chiral SalanCr(III) complexes all play significant roles in controlling polymer stereochemistry and enantioselectivity. Furthermore, a relationship between polycarbonate enantioselectivity and its head‐to‐tail linkages in relation to regioselective ring‐opening of the epoxide was also discussed on the basis of stereochemical studies of PPCs derived from the copolymerization of CO2 with chiral PO at various conditions. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6102–6113, 2008

Synthesis of novel paracyclophanes with linear P,N-containing spacers

Condensation of bis(hydroxymethyl)mesityl-and bis(hydroxymethyl)phenylphosphines with N,N′-disubstituted bis(4-aminophenyl)methanes and bis(4-amino-3-carboxyphenyl)methane occurred as covalent self-assembly spontaneously giving a mixture of trans-and cis-diastereomers of 1,5,19,23-tetra-R′-3,21-di-R-1,5,19,23-tetraaza-3,21-diphospha[5.1.5.1]paracyclophanes as the major products. The trans-isomer (R is mesityl; R′ is methyl) was isolated in the individual state and structurally characterized by X-ray diffraction analysis. Sulfurization of macrocyclic diphosphines (R = Ph; R′ is 3-pyridylmethyl or 4-pyridylmethyl) gave the corresponding diphosphine disulfides, the trans-stereoisomer being isolated in the individual state.

Glucose-derived Amadori compounds of glutathione

Under the chromatographic conditions used in these studies we observed time- and concentration-dependent formation of N-1-Deoxy-fructos-1-yl glutathione as the major glycation product formed in the mixtures of GSH with glucose. N-1-Deoxy-fructos-1-yl glutathione had a characteristic positively charged ion with m/z=470 Th in its LC-MS spectra. Mixtures of glutathione disulfide and glucose generated two compounds: N-1-Deoxy-fructos-1-yl GSSG (m/z=775 Th) as major adduct and bis di-N, N'-1-Deoxy-fructos-1-yl GSSG (m/z=937 Th) as the minor one. All three compounds showed a resonance signal at 55.2 ppm in the 13C-NMR spectra as C1 methylene group of deoxyfructosyl, which represents direct evidence that they are Amadori compounds. All three compounds purified from GSSG/Glc or GSH/Glc mixtures also showed LC-MS/MS fragmentation patterns identical to those of the synthetically synthesized N-1-Deoxy-fructos-1-yl glutathione, N-1-Deoxy-fructos-1-yl GSSG and bis di-N, N'-1-Deoxy-fructos-1-yl GSSG. N-1-Deoxy-fructos-1-yl glutathione was shown to be a poor substrate for glutathione peroxidase (6.7% of the enzyme's original specific activity) and glutathione-S-transferase (25.7% of the original enzyme's specific activity). Glutathione reductase failed to recycle the disulfide bond within the structure of di-substituted bis di-N, N'-1-Deoxy-fructos-1-yl GSSG. It showed only 1% of the original enzyme's specific activity, but retained its ability to reduce the disulfide bond within the structure of N-1-Deoxy-fructos-1-yl GSSG by 57% of its original specific activity. Since the GSH concentration in diabetic lens is significantly decreased and the glucose concentration can increase 10-fold and higher, the formation of Amadori products of the different forms of glutathione with this monosaccharide may be favored under these conditions and could contribute to a lowering of glutathione levels and an increase of oxidative stress observed in diabetic lens.

2-Aminopyrimidine directed self-assembly of zinc porphyrins containing bulky 3,5-di-tert-butylphenyl groups.

The 2-aminopyrimidin-5-yl ligand is revealed to be a promising candidate for the construction of supramolecular porphyrin arrays with broad absorption bands for efficient light-harvesting. 10-Mono- and 10,20-di(2-aminopyrimidin-5-yl) derivatives of 5,15-bis(3,5-di-tert-butylphenyl)porphyrin have been synthesized in high yield. Their Zn(II) salts show variable concentration and temperature-dependent UV/vis spectra in solution, consistent with supramolecular aggregation. Whereas the FAB mass spectra of the monosubsituted derivative in toluene suggest the formation of a tetramer at high concentrations and low temperatures (estimated association free enthalpy Delta H = 220 +/- 10 kJ/mol), the larger splitting of the Sorret band (ca. 40 nm) in the variable temperature UV/vis spectra of the disubstituted bis(3,5-di-tert-butylphenyl)porphyrin is indicative of yet higher aggregates involving both 2-aminopyrimidin-5-yl groups. The tetrameric nature of the monosubsituted derivative is confirmed by X-ray analysis, which reveals that two of the 2-aminopyrimidin-5-yl groups are encapsulated by the aggregate and consequently are prevented from undergoing hydrogen bonding. NMR studies show there is no exchange of the 2-aminopyrimidin-5-yl groups, so the tetramer is rigid, which is confirmed by molecular modeling calculations. The tetramer formation is governed by pi-pi interactions, metal coordination, and hydrogen bonding. The di(2-aminopyrimidin-5-yl) derivative forms strongly scattering solutions, which upon standing form green flocculate precipitates, reminiscent of shaken suspensions of bacteriochlorophyll c.

Asymmetric imidation of organic selenides into selenimides

Treatment of aryl benzyl selenides with [ N-( p-toluenesulfonyl)imino]phenyliodinane [TsNIPh] in the absence or presence of copper(I) salt in toluene or acetonitrile affords the corresponding N-tosylselenimides in 31–46% yield. When the reaction is carried out in the presence of optically active 4,4′-disubstituted bis(oxazoline) as a ligand together with molecular sieves, enantioselective imidation occurs to give optically active N-tosylselenimides and the best result is obtained from benzyl 2-naphthyl selenide (64% yield and 36% ee). Similar treatment of allylic selenides gives the corresponding optically active allylic amides (up to 71% yield and 30% ee). In the case of diastereoselective imidation, the reaction of diaryl selenides bearing a chiral oxazolinyl moiety with TsNIPh or Chloramine–T trihydrate [TsN(Cl)Na·3H 2O] has been successfully carried out to give the corresponding optically active N-tosylselenimides in good yields (up to 97% isolated yield and 76% de). The absolute configuration around the selenium atom of (4 S)- Se-[2-(4-isopropyloxazolin-2-yl)phenyl]- Se-phenyl- N-( p-toluenesulfonyl)selenimide [(4 S)- 13], obtained by diastereoselective imidation of the corresponding selenide with Chloramine–T trihydrate, has been determined to be S by X-ray crystallographic analysis, from the result of which an ionic reaction pathway involving a chloroselenonium ion intermediate is proposed.

(Aryl)(2-furyl)alkanes and their derivatives, 20. Synthesis of symmetric bis- and tris(2-furyl)methanes

New methods for the synthesis of symmetric 5,5'-disubstituted bis- and 5,5',5-trisubstituted tris(2-furyl)methanes have been developed. Symmetric bis(2-furyl)methanes were prepared from 5-substituted 2-furylmethanols in the presence of concentrated perchloric acid. The attempted synthesis of (aryl)(bis(2-furyl))methanes from (aryl)(2-furyl)methanols in the presence of acid catalysts failed. The reaction of 5-substituted 2-furaldehydes with ethylene glycol in the presence of strong acid catalysts led to tris(2-furyl)methanes. Plausible mechanisms of these transformations are discussed.

Preparation of bis(dithienothiophene) derivatives for organic thin film transistors

The synthesis of two α,α′-disubstituted bis(dithienothiophene) (BDT) derivatives is described. These have been deposited by vacuum sublimation as the active layers in organic thin film transistors (TFTs). The devices exhibit high ON/OFF ratios and preliminary studies show mobilities of 1 X 10 −3 and 2 x 10 −2 cm 2 V −1 s −1 respectively for dithiohexyl (DTH-BDT) and dioctyl (DO-BDT) substituted bis(dithienothiophene). DTH-BDT is found to be considerably more soluble than the unsubstituted BDT.

Synthesis and Structure of Acyclic Bis(ketenimine) Complexes of Zirconium

Mono- and disubstituted bis(ketenimine) complexes of zirconium (1 and 2, respectively) can be readily prepared by reaction of these ligands (3) with Zr(NMe)4 or, in some cases, the homoleptic tetrabenzyl derivative ZrBn4. Treatment of 1 (Ar = Ph, p-CF3Ph; X = NMe2) with Me2NH·HCl and of 2 (Ar = Ph, X = NMe2) with either Me2NH·HCl or TMSCl provides the corresponding chloro derivatives in high yield. Alkyl derivatives of 2 (X = Me, Bn) can be readily prepared by reaction of the corresponding chloro derivatives with Grignard or organolithium reagents. Monocyclopentadienyl bis(ketenimine) complexes 4 (Ar = Ph, p-CF3Ph; Cp = η5-C5H5, η5-C9H7; X = Cl) were prepared from 1 (Ar = Ph, p-CF3Ph; X = Cl) by reaction with CpLi or IndLi in high yield, and methyl derivatives 4 (Ar = Ph, p-CF3Ph; Cp = η5-C5H5, η5-C9H7; X = Me) were accessible by treatment of the chloro precursors with methyllithium. The X-ray structure of 2 (Ar = Ph; X = NMe2) reveals a distorted-octahedral geometry in which the bis(ketenimine) ligands are σ-bound to the metal and the dimethylamido groups are cis to one another, and the corresponding dichloro derivative also adopts a similar structure in the solid state, whereas the bis(ketenimine) ligands adopt a distorted, η5 binding mode in the monoindenyl derivative 4 (Ar = Ph; Cp = η5-C9H7; X = Cl). Enantiomers of 2 (Ar = Ph, X = Cl) readily interconvert in solution via a Bailar-twist mechanism, as revealed by variable-temperature 1H NMR spectroscopic studies; activation parameters for this process were determined (ΔH‡ = 9.0 ± 0.45 kcal mol-1; ΔS‡ = −9.9 ± 1.0 cal mol-1 K-1).

Catalytic asymmetric sulfimidation of 1,3-dithianes

A direct catalytic sulfimidation of 1,3-dithianes to the corresponding chiral monosulfimides with N-(p-tolylsulfonyl)imino(phenyl)iodinane (TsNIPh) using a catalytic amount of copper(I) triflate (CuOTf) and a chiral 4,4′-disubstituted bis(oxazoline) as ligand has been developed. The reaction affords the chiral monosulfimides in good yield and with moderate enantioselectivity (up to 40% ee).