Zwitterionic Products Research Articles

A synthetic approach towards drug modification: 2-hydroxy-1-naphthaldehyde based imine-zwitterion preparation, single-crystal study, Hirshfeld surface analysis, and computational investigation.

The current work is about the modification of primary amine functionalized drugs, pyrimethamine and 4-amino-N-(2,3-dihydrothiazol-2-yl)benzenesulfonamide, via condensation reaction with 2-hydroxy-1-naphthaldehyde to produce new organic zwitterionic compounds (E)-1-(((4-(N-(2,3-dihydrothiazol-2-yl)sulfamoyl)phenyl)iminio)methyl)naphthalen-2-olate (DSPIN) and (E)-1-(((4-amino-5-(4-chlorophenyl)-6-ethylpyrimidin-2-yl)iminio)methyl)naphthalen-2-olate (ACPIN) in methanol as a solvent. The crystal structures of both compounds were confirmed to be imine-based zwitterionic products via single-crystal X-ray diffraction (SC-XRD) analysis which indicated that the stabilization of both crystalline compounds is achieved via various noncovalent interactions. The supramolecular assembly in terms of noncovalent interactions was explored by the Hirshfeld surface analysis. Void analysis was carried out to predict the crystal mechanical response. Compound geometries calculated in the DFT (Density Functional Theory) study showed reasonably good agreement with the experimentally determined structural parameters. Frontier molecular orbital (FMO) analysis showed that the DSPIN HOMO/LUMO gap is by 0.15 eV smaller than the ACPIN HOMO/LUMO gap due to some destabilization of the DSPIN HOMO and some stabilization of its LUMO. The results of the charge analysis implied formation of intramolecular hydrogen bonds and suggested formation of intermolecular hydrogen bonding and dipole-dipole and dispersion interactions.

Discovery of 35 novel classes of per- and polyfluoroalkyl substances in representative commercial fluorinated products in China

Per- and polyfluoroalkyl substances (PFAS) have received increasing scientific and regulatory attention due to their global distribution and health hazards. However, little is known about the PFAS composition of fluorinated products commercially available in China. In this study, a sensitive and robust analytical method was proposed for the comprehensive characterization of PFAS in aqueous film-forming foam and fluorocarbon surfactants in the domestic market based on liquid chromatography-high resolution mass spectrometry in full scan acquisition mode followed by parallel reaction monitoring mode. Consequently, a total of 102 PFAS from 59 classes were elucidated, of which 35 classes are reported for the first time, including 27 classes of anionic, seven classes of zwitterionic, and one class of cationic PFAS. The anionic-type products are mainly C6 fluorotelomerization-based (FT-based) PFAS. Perfluorooctanoic acid and perfluorooctane sulfonate are negligible, while some known electrochemical fluorination-based long-chain precursors in zwitterionic products are worthy of concern because of their high abundance and potential degradation. New precursors detected in zwitterionic products are FT-based PFAS, for example, 6:2 FTSAPr-AHOE and 6:2 FTSAPr-diMeAmPrC. The structural elucidation of PFAS in commercial products facilitates a better assessment of human exposure and environmental release.

From nonionic to zwitterionic: Novel CO2-responsive zwitterionic wormlike micelles based on zwitterionic surfactant and bola-type asymmetric diamine

CO2 enhanced oil recovery (CO2-EOR) is one of the CO2 utilization methods which can also geo-sequestrate greenhouse gases. Due to the weak adsorption on rock surface and excellent viscoelasticity performance, CO2-responsive zwitterionic wormlike micelles (WLMs) has been recognized as a promising method to control CO2 channeling. A novel CO2 responsive zwitterionic WLMs was developed by blending N-octadecyl-N,N-dimethyl-3-ammonio-2-hydroxy-1-propane-sulfonate (OHSB), N,N,2,2-tetramethyl-1,3-propanediamine (TADPA) and sodium salicylate (NaSal). The responsive behaviors induced by varying agents (CO2 and HCl) are systematically studied by rheology tests and cryo-TEM measurements. The molecular structures of products are confirmed by 1H and 13C NMR. Moreover, the responsive mechanism is discussed in detail. The OHSB/NaSal/TADPA system shows morphological transformations between spherical micelles (a good flowing capacity) and WLMs (conducive to plugging) before and after purging CO2. The viscoelasticity and molecular structure of the system with CO2 bubbling is different from that with HCl titration, because TADPA molecules can react with CO2 to form a novel zwitterionic product: NH+(CH3)2-CH2-C(CH3)2-CH2-NHCO2− (TAH+DPACO2−, 78.95 %–83.52 %). This work provides a new strategy for the design of CO2-responsive zwitterionic WLMs and their applications in CO2 utilization schemes, including clean fracturing, mobility control, and CO2 foam flooding, etc.

Chemoenzymatic Synthesis of 5-Methylpsilocybin: A Tryptamine with Potential Psychedelic Activity.

A novel analogue of psilocybin was produced by hybrid chemoenzymatic synthesis in sufficient quantity to enable bioassay. Utilizing purified 4-hydroxytryptamine kinase from Psilocybe cubensis, chemically synthesized 5-methylpsilocin (2) was enzymatically phosphorylated to provide 5-methylpsilocybin (1). The zwitterionic product was isolated from the enzymatic step with high purity utilizing a solvent-antisolvent precipitation approach. Subsequently, 1 was tested for psychedelic-like activity using the mouse head-twitch response assay, which indicated activity that was more potent than the psychedelic dimethyltryptamine, but less potent than that of psilocybin.

Cover Feature: Ishikawa's Reagent – a Valuable Source for Fluoroorganic Iminium Salts (Z. Anorg. Allg. Chem. 4/2021)

The cover picture shows the zwitterionic iminium phosphate [P(C2F5)2F3{C(NEt2)(CHF-CF3)] obtained by the reaction of Ishikawa's reagent Et2N-CF2-CHF-CF3 with the Lewis-acidic P(C2F5)2F. The fluorinating Ishikawa's reagent most likely transfers a fluoride ion onto the phosphorus center, transiently forming [Et2N=CF-CHF-CF3][P(C2F5)2F2]. The α-fluorine atom of the iminium cation [Et2N=CF-CHF-CF3]+ is labile towards substitution. Subsequently, insertion of the phosphate(III) anion into the activated C−F bond delivers the zwitterionic product (https://doi.org/10.1002/zaac.202000198).

Synthesis, Structures, and Transformations of Bridging and Terminally-Coordinated Trimethylammonioalkenyl Ligands in Zwitterionic Pentaruthenium Carbido Carbonyl Complexes.

Reactions of the pentaruthenium cluster complexes Ru5(μ5-C)(CO)15 (5), Ru5(μ5-C)(CO)14[μ-η2-O═C(NMe2)](μ-H) (6), and Ru5(μ5-C)(CO)15Cl(μ-H) (7) with ethyne (C2H2) in the presence of Me3NO yielded the zwitterionic complexes Ru5(μ5-C)(CO)13[μ-η2-CHCH(NMe3)] (8), Ru5(μ5-C)(CO)13[μ-η2-O═C(NMe2)](η1-E-CH═CH(NMe3)(μ-H) (9), and Ru5(μ5-C)(CO)13Cl[η1-E-CH═CH(NMe3)](μ-H) (11). Each product contains a positively charged trimethylammonioethenyl ligand, CH═CH(+NMe3), that is derived from a 2-trimethylammonioethenide, -CH═CH(+NMe3), zwitterion that formally has a positive charge on the nitrogen atom and a negative charge on the terminal enyl carbon atom. The trimethylammonioethenyl ligand, CH═CH(+NMe3) in 8 is a η2-ligand that bridges a Ru-Ru bond on a basal edge of the square-pyramidal Ru5 cluster by a combination of σ + π cooordination of the ethenyl group. Compounds 9 and 11 each contain a η1-terminally coordinated [η1-E-CH═CH(+NMe3)] ligand with an E stereochemistry at the C═C double bond in open Ru5 cluster complexes. Compound 9 was decarbonylated to yield the compound Ru5(μ5-C)(CO)12[μ-η2-O═C(NMe2)][μ-η2-CH═CH(NMe3)](μ-H) (10) containing a η2-bridging CHCH(+NMe3) ligand. Compound 10 was converted back to 9 by the addition of CO. Two zwitterionic products, Ru5(μ5-C)(CO)14[η1-E-CH═CH(NMe3)] (12) and Ru5(μ5-C)(CO)15[η1-E-CH═CH(NMe3)] (13), were obtained by the addition of CO to 8. Compound 12 is an intermediate en route to 13. Compound 12 contains a terminally coordinated η1-E-CH═CH(+NMe3) ligand on one of the basal Ru atoms of a square-pyramidal Ru5 cluster. Compound 13 also contains a terminally coordinated η1-E-CH═CH(+NMe3) ligand on the wing-tip bridging Ru atom of a butterfly Ru4C cluster. Treatment of 6 with methyl propiolate (HC≡CCO2Me) yielded the zwitterionic complex Ru5(μ5-C)(CO)13[μ-η2-O═C(NMe2)][η1-E-(MeO2C)C═C(H)NMe3](μ-H) (14) that is structurally similar to 9 but contains a η1-E-(MeO2C)C═C(H)(+NMe3) ligand. Compound 14 eliminated the NMe3 group to yield the compounds Ru5(μ5-C)(CO)13[μ-η2-O═C(NMe2)][μ-η2-(MeO2C)HC═CH] (15) which contains a bridging methoxycarbonyl-substituted alkenyl ligand and the known compound Ru5(μ5-C)(CO)13[μ-η2-O═C(NMe2)](HNMe2)(μ-H) (16).

B-H and O-H bonds activation via a single electron transfer of frustrated radical pairs.

The rare examples of B-H bond activation in a frustrated radical pair regime have been observed by treatment of TEMPO radicals with Piers' borane HB(C6F5)2 or bis-borane, respectively. The resulting concomitant formation of zwitterionic products and geminal N/B frustrated Lewis pairs implied a one electron process. In addition, the reaction of a TEMPO/B(C6F5)3 pair with H2O·B(C6F5)3 was assumed to involve one-electron reduction of water. Our results provide insights into chemical bond (e.g. B-H and O-H) activation via a single electron transfer.

Real-time monitoring of intracellular pH in live cells with fluorescent ionic liquid

Real-time monitoring of intracellular pH is of great significance due to its essential role in physiological and pathological processes. In present work, the ionic liquid (IL) N-methyl-6-hydroxyquinolinium bis(trifluoromethylsulfonyl) imide ([6MQc][NTf2]) is proposed as a fluorescence probe for the quantitative imaging of intracellular pH in response to external stimuli. The fluorescence of the IL [6MQc][NTf2] exhibits a sensitive response to pH variations, as the deprotonation of [6MQc][NTf2] generates the highly fluorescent zwitterionic product [6MQz]. pH fluctuations in the range of 6.0–7.5 can be accurately sensed by monitoring the fluorescence change at 555 nm. Moreover, this IL probe exhibits favorable biocompatibility, excellent anti-photobleaching properties, and high tolerance to ionic strength. Using the IL probe, real-time sensing of hypoxia- and drug-induced intracellular pH changes in MCF-7 cells is achieved.

Ring-opening of Epoxides Mediated by Frustrated Lewis Pairs.

Treatment of the preorganized frustrated Lewis pairs (FLPs) tBu2 PCH2 BPh2 (1) and o-Ph2 P(C6 H4 )BCat (Cat=catechol) (4) with 2-methyloxirane, 2-phenyloxirane and 2-(trifluoromethyl)oxirane resulted in epoxide ring-opening to yield the six- and seven-membered heterocycles 2 a-c and 5 a-c, respectively. These zwitterionic products were characterized spectroscopically, and compounds 2 a, 2 b, 5 a and 5 c were structurally characterized by single-crystal X-ray structure analyses. Based on computational and kinetic studies, the mechanism of these reactions was found to proceed via activation of the epoxide by the Lewis acidic borane moiety followed by nucleophilic attack of the phosphine of a second FLP molecule. The resulting chain-like intermediates afford the final cyclic products by ring-closure and concurrent release of the second equivalent of FLP that behaves as catalyst in this reaction.

Rational design of FLP catalysts for reversible H2 activation: A DFT study of the geometric and electronic effects

Frustrated Lewis pairs (FLPs) emerge as a new type of bifunctional metal-free catalysts for reversible H2 activation, which is important for the storage and liberation of H2 or further controllable utilizing chemical fuels via hydrogenation/dehydrogenation. Herein, a DFT study was conducted to understand the geometric factors and electronic effects of FLPs on reversible H2 activation. The Lewis base group mainly contributes to the proton attachment, and influences the kinetics of the H2 activation. The Lewis acid group mainly relates to the hydride attachment, and affects more significantly on the thermodynamics of H2 activation. The dimer and quenched structure of FLPs also have a degree of influence on the performance of catalyzed H2 activation. A series of FLPs with para-substituted phenyl derivatives as LA groups were designed and evaluated. The results indicate that the variation of LA groups has significant impact on thermodynamic energy of dihydrogen adducts but insignificant effect on kinetics. Moreover, we found the thermodynamic energy of products has a good linear relationship with Hammett substituent constants. The solvent effect on H2 activation was also studied, and polar solvent is beneficial for zwitterionic products. These results should provide deeper insight to understand the relation between FLPs structure and reactivity, which is critical for rational design of more efficient FLPs catalysts for reversible H2 activation.

Reactions of cyclohexene-annulated 3а,6а-diaza-1,4-diphosphapentalene with sulfur, selenium, and CS2: structural features of zwitterionic products

The reactions of b- and f-face cyclohexene-annulated 3a,6a-diaza-1,4-diphosphapentalene (CADDP) with elemental sulfur and selenium result in the addition of two chalcogen atoms to one phosphorus atom of CADDP. A specific feature of these structures is that the diazadiphosphapentalene skeleton retains planar geometry, with a significant elongation of the N—P bond. These compounds are zwitterions, as evidenced by their electronic structures, with considerable delocalization of the negative charge in the PS2 (PSe2) moieties and of the positive charge in the diazaphosphole ring. The reaction of CADDP with carbon disulfide is a more complicated process accompanied by the decomposition of the CS2 molecule to form a molecule containing three structurally different CADDP moieties, one of which is a stabilized carbene complex.

Understanding the Subtleties of Frustrated Lewis Pair Activation of Carbonyl Compounds by N-Heterocyclic Carbene/Alkyl Gallium Pairings.

This study reports the use of the trisalkylgallium GaR3 (R=CH2 SiMe3 ), containing sterically demanding monosilyl groups, as an effective Lewis-acid component for frustrated Lewis pair activation of carbonyl compounds, when combined with the bulky N-heterocyclic carbene 1,3-bis(tert-butyl)imidazol-2-ylidene (ItBu) or 1,3-bis(tert-butyl)imidazolin-2-ylidene (SItBu). The reduction of aldehydes can be achieved by insertion into the C=O functionality at the C2 (so-called normal) position of the carbene affording zwitterionic products [ItBuCH2 OGaR3 ] (1) or [ItBuCH(p-Br-C6 H4 )OGaR3 ] (2), or alternatively, at its abnormal (C4) site yielding [aItBuCH(p-Br-C6 H4 )OGaR3 ] (3). As evidence of the cooperative behaviour of both components, ItBu and GaR3 , neither of them alone are able to activate any of the carbonyl-containing substrates included in this study NMR spectroscopic studies of the new compounds point to complex equilibria involving the formation of kinetic and thermodynamic species as implicated through DFT calculations. Extension to ketones proved successful for electrophilic α,α,α-trifluoroacetophenone, yielding [aItBuC(Ph)(CF3 )OGaR3 ] (7). However, in the case of ketones and nitriles bearing acidic hydrogen atoms, C-H bond activation takes place preferentially, affording novel imidazolium gallate salts such as [{ItBuH}+ {(p-I-C6 H4 )C(CH2 )OGaR3 }- ] (8) or [{ItBuH}+ {Ph2 C=C=NGaR3 }- ] (12).

Unusual borane addition to conjugated dienylphosphanes under frustrated Lewis pair conditions.

Dimesitylphosphinoisoprene 9a reacts with a series of R-B(C6F5)2 boron Lewis acids by isomerization and subsequent 1,4-P/B addition to give the heterocyclic phosphonium/borate zwitterionic products 13. Subsequent hydride abstraction from the isoprenyl derived methyl group by trityl cation proceeds with elimination of the R-B(C6F5)2 reagent to give the heterocyclic phosphonium system 20.

Synthesis and structure of stable water-soluble phosphonium alkanoate zwitterions derived from 1,3,5-triaza-7-phosphaadamantane

1,3,5-triaza-7-phosphaadamantane (PTA) was shown to form phosphonium alkanoate zwitterions with unsaturated dicarboxylic acids in water in the absence of strong acids. Solid-state structures of the phosphonium salt (1) derived from maleic or fumaric acids and that of the zwitterionic product (2) of the reaction of PTA with citraconic and mesaconic acids were determined by single-crystal X-ray diffraction. DFT calculations gave insight into the mechanism of the reaction, including the relative reactivity of the four dicarboxylic acids, and revealed the reasons for the lack of phosphonium salt formation by PTA in strongly acidic aqueous solutions.

ChemInform Abstract: Frustrated Lewis Pairs: From Concept to Catalysis

AbstractReview: 109 refs.

Frustrated Lewis pair-like reactions of nucleophilic palladium carbenes with B(C6F5)3.

The reactions of two nucleophilic palladium carbene complexes with the strong Lewis acid B(C6F5)3 afforded two zwitterionic products. One of them features a remote nucleophilic attack at the para-carbon of the supporting ligand, while the other indicates C-F activation of B(C6F5)3. Both behaviours are reminiscent of the reactivity of frustrated Lewis pairs due to the steric inaccessibility of the nucleophilic carbon center, but are unprecedented for transition metal carbene complexes. Furthermore, when those reactions are carried out in the presence of H2, products resulting from H2 splitting are observed.

Frustrated Lewis pairs: from concept to catalysis.

CONSPECTUS: Frustrated Lewis pair (FLP) chemistry has emerged in the past decade as a strategy that enables main-group compounds to activate small molecules. This concept is based on the notion that combinations of Lewis acids and bases that are sterically prevented from forming classical Lewis acid-base adducts have Lewis acidity and basicity available for interaction with a third molecule. This concept has been applied to stoichiometric reactivity and then extended to catalysis. This Account describes three examples of such developments: hydrogenation, hydroamination, and CO2 reduction. The most dramatic finding from FLP chemistry was the discovery that FLPs can activate H2, thus countering the long-existing dogma that metals are required for such activation. This finding of stoichiometric reactivity was subsequently evolved to employ simple main-group species as catalysts in hydrogenations. While the initial studies focused on imines, subsequent studies uncovered FLP catalysts for a variety of organic substrates, including enamines, silyl enol ethers, olefins, and alkynes. Moreover, FLP reductions of aromatic anilines and N-heterocycles have been developed, while very recent extensions have uncovered the utility of FLP catalysts for ketone reductions. FLPs have also been shown to undergo stoichiometric reactivity with terminal alkynes. Typically, either deprotonation or FLP addition reaction products are observed, depending largely on the basicity of the Lewis base. While a variety of acid/base combinations have been exploited to afford a variety of zwitterionic products, this reactivity can also be extended to catalysis. When secondary aryl amines are employed, hydroamination of alkynes can be performed catalytically, providing a facile, metal-free route to enamines. In a similar fashion, initial studies of FLPs with CO2 demonstrated their ability to capture this greenhouse gas. Again, modification of the constituents of the FLP led to the discovery of reaction systems that demonstrated stoichiometric reduction of CO2 to either methanol or CO. Further modification led to the development of catalytic systems for the reduction of CO2 by hydrosilylation and hydroboration or deoxygenation. As each of these areas of FLP chemistry has advanced from the observation of unusual stoichiometric reactions to catalytic processes, it is clear that the concept of FLPs provides a new strategy for the design and application of main-group chemistry and the development of new metal-free catalytic processes.

Novel organo phosphorus–selenium heteroatom compounds from selenation of diamines

Reaction of Woollins' reagent (WR) with trans-1,2-cyclohexanediamine or 1,3-cyclohexanediamine, followed by treatment with o-xylylenedibromide in THF at room temperature surprisingly led to 3-phenyl-1,5-dihydrobenzo[e][1,3,2]diselenaphosphepine 3-selenide (3). However, using o-phenylenediamine, the same product together with 1,4-dihydrobenzo[d][1,2]diselenine (9) was obtained. Furthermore, treating WR with N,N′-dibenzylethane-1,2-diamine gave rise to 1,3-dibenzyl-2-phenyl-1,3,2-diazaphospholidine 2-selenide (10) and a zwitterionic product N-benzyl-N-(2-(benzylammonio)ethyl)-P-phenylphosphonamidodiselenoate (11). Unexpectedly, WR reacted with 2,2′-disulfanediyldianiline under identical conditions affording the known product: 2-phenyl-2,3-dihydrobenzo[d][1,3,2]thiazaphosphole 2-selenide (13). Three representative X-ray structures are reported.

Halogen Addition to a Frustrated Lewis Pair

AbstractThe reactive intramolecular frustrated Lewis pair (FLP) Mes2PCH2CH2B(C6F5)2 reacts rapidly with thionyl chloride to yield the zwitterionic chlorination product [Mes2PCl+]CH2–CH2[BCl(C6F5)2–]. Analogous zwitterionic products were obtained by the reaction of the FLP with chlorine or bromine. Compounds [Mes2PX+]CH2CH2[BX(C6F5)2–] (X = Cl, Br) were characterized by X‐ray crystal structure analyses.

Reaction of Frustrated Lewis Pairs with Ketones and Esters

The frustrated Lewis pair (FLP) Mes(2)PCH(2)CH(2)B(C(6)F(5))(2) (1) reacts with an enolizable conjugated ynone by 1,4-addition involving enolate tautomerization to give an eight-membered zwitterionic heterocycle. The conjugated endione PhCO-CH=CH-COPh reacts with the intermolecular FLP tBu(3)P/B(C(6)F(5))(3) by a simple 1,4-addition to an enone subunit. The same substrate undergoes a more complex reaction with the FLP 1 that involves internal acetal formation to give a heterobicyclic zwitterionic product. FLP 1 reacts with dimethyl maleate by selective overall addition to the C=C double bond to give a six-membered heterocycle. It adds analogously to the triple bond of an acetylenic ester to give a similarly structured six-membered heterocycle. The intermolecular FLP P(o-tolyl)(3)/B(C(6)F(5))(3) reacts analogously with acetylenic ester by trans-addition to the carbon-carbon triple bond. An excess of the intermolecular FLP tBu(3)P/B(C(6)F(5))(3), which contains a more nucleophilic phosphane, reacts differently with acetylenic ester examples, namely by O-C(alkyl) bond cleavage to give the {R-CO(2)[B(C(6)F(5))(3)](2)(-)}[alkyl-PtBu(3)(+)] salts. Simple aryl or alkyl esters react analogously by using the borane-stabilized carboxylates as good leaving groups. All essential products were characterized by X-ray diffraction.