Basic Amine Research Articles

Porphycenes as broad-spectrum antimicrobial photosensitizers. Potentiation with potassium iodide

Two novel meso-tetrasubstituted porphycenes (Pc-Cbz and Pc-NEt2) have been synthesized by palladium-catalyzed Suzuki cross-coupling reactions over 9,10,19,20-tetrakis(4-iodophenyl)porphycene. Pc-Cbz contains four carbazole groups on the periphery of the tetrapyrrolic macrocycle. Instead, Pc-NEt2 presents four basic tertiary amine substituents, which can be protonated at physiological pH, acquiring four positive charges. Both photosensitizers (PSs) were designed to evaluate the effect of different substitution patterns on the photodynamic inactivation of microorganisms. Their absorption and fluorescence properties were almost unmodified regardless of the substituent groups on the periphery. The characteristic red emission makes them promising fluorescent probes for cell imaging. Moreover, both macrocycles were able to generate reactive oxygen species by both photodynamic mechanisms under aerobic light irradiation. The photokilling action of these PSs was assessed in vitro against Candida albicans (yeast), Staphylococcus aureus (Gram-positive bacterium), and Escherichia coli (Gram-negative bacterium). Our results demonstrate that the peripheral substitution significantly affected the photoinactivation performance. Thus, Pc-NEt2 was more effective than Pc-Cbz in killing microorganisms using lower concentrations and shorter irradiation periods, evidencing that external substitution is a main structural feature. Also, the photoinactivation efficiency mediated by these porphycenes was potentiated by adding KI. Under these conditions, a complete eradication of all pathogenic microorganisms was obtained by combining Pc-NEt2 and KI. Therefore, Pc-NEt2 can be used as an effective broad-spectrum antimicrobial PS. Accordingly, this work stands out as a promising starting point for the design of new porphycene-based PSs for photodynamic inactivation (PDI) of microorganisms. Our outcomes also disclose that the combination of these PSs with KI is an important factor in order to improve the PDI treatments and the current antimicrobial therapies.

Fluorescent Molecular Logic Gates and Pourbaix Sensors in Polyacrylamide Hydrogels.

Polyacrylamide hydrogels formed by free radical polymerisation were formed by entrapping anthracene and 4-amino-1,8-naphthalimide fluorescent logic gates based on photoinduced electron transfer (PET) and/or internal charge transfer (ICT). The non-covalent immobilisation of the molecules in the hydrogels resulted in semi-solid YES, NOT, and AND logic gates. Two molecular AND gates, examples of Pourbaix sensors, were tested in acidic aqueous methanol with ammonium persulfate, a strong oxidant, and displayed greater fluorescence quantum yields than previously reported. The logic hydrogels were exposed to aqueous solutions with chemical inputs, and the fluorescence output response was viewed under 365 nm UV light. All of the molecular logic gates diffuse out of the hydrogels to some extent when placed in solution, particularly those with secondary basic amines. The study exemplifies an effort of taking molecular logic gates from homogeneous solutions into the realm of solid-solution environments. We demonstrate the use of Pourbaix sensors as pE-pH indicators for monitoring oxidative and acidic conditions, notably for excess ammonium persulfate, a reagent used in the polymerisation of SDS-polyacrylamide gels.

Total Synthesis of the Tetracyclic Pyridinium Alkaloid epi-Tetradehydrohalicyclamine B.

The first total synthesis of a tetracyclic marine pyridinium alkaloid hinged on recent advances in chemoselectivity management: While many classical methods failed to afford the perceptively simple pyridine-containing core of the target, nickel/iridium photoredox dual catalysis allowed the critical C-C bond to be formed in good yield. Likewise, ring closing alkyne metathesis (RCAM) worked well in the presence of the unhindered pyridine despite the innately Lewis acidic Mo(+6) center of the alkylidyne catalyst. Finally, an iridium catalyzed hydrosilylation was uniquely effective in reducing a tertiary amide without compromising an adjacent pyridine and the lateral double bonds; this transformation is largely without precedent. The second strained macrocycle enveloping the core was closed by intramolecular N-alkylation with formation of the pyridinium unit; the reaction proceeded site- and chemoselectively in the presence of an a priori more basic tertiary amine.

Total Synthesis of the Tetracyclic Pyridinium Alkaloid epi‐Tetradehydrohalicyclamine B

AbstractThe first total synthesis of a tetracyclic marine pyridinium alkaloid hinged on recent advances in chemoselectivity management: While many classical methods failed to afford the perceptively simple pyridine‐containing core of the target, nickel/iridium photoredox dual catalysis allowed the critical C−C bond to be formed in good yield. Likewise, ring closing alkyne metathesis (RCAM) worked well in the presence of the unhindered pyridine despite the innately Lewis acidic Mo(+6) center of the alkylidyne catalyst. Finally, an iridium catalyzed hydrosilylation was uniquely effective in reducing a tertiary amide without compromising an adjacent pyridine and the lateral double bonds; this transformation is largely without precedent. The second strained macrocycle enveloping the core was closed by intramolecular N‐alkylation with formation of the pyridinium unit; the reaction proceeded site‐ and chemoselectively in the presence of an a priori more basic tertiary amine.

Palladium-catalysed selective oxidative amination of olefins with Lewis basic amines.

Amines are prominent in natural products, pharmaceutical agents and agrochemicals. Moreover, they are synthetically valuable building blocks for the construction of complex organic molecules and functional materials. However, amines, especially aliphatic and aromatic amines with free N-H bonds, tend to coordinate with transition metals and deactivate the catalyst, posing a tremendous challenge to applying Lewis basic amines in the amination of olefins. Here we present an example of oxidative amination of simple olefins with various Lewis basic amines. The combination of a palladium catalyst, 2,6-dimethyl-1,4-benzoquinone and a phosphorous ligand leads to the efficient synthesis of alkyl and aryl allylamines. A series of allylamines were obtained with good yields and excellent regio- and stereoselectivities. Intramolecular amination to synthesize tetrahydropyrrole and piperidine derivatives was also realized. Mechanistic investigations reveal that the reaction undergoes allylic C(sp3)-H activation and subsequent functionalization.

Synthesis of Tertiary Amines through Extrusive Alkylation of Carbamates.

Basic amines are key elements of many biologically active natural products and pharmaceuticals. Given their inherent reactivity, it is often necessary to protect basic amines during target-directed synthesis, which results in wasteful protection/deprotection sequences. We report a step-economical approach enabling the protection of secondary amines as carbamates prior to their conversion to tertiary amines via the formal extrusion of CO2. This method is applied to the synthesis of iboga alkaloids (±)-conodusine A and (±)-conodusine B.

Impact of Fluoroalkyl Substituents on the Physicochemical Properties of Saturated Heterocyclic Amines.

The physicochemical properties (pKa (H), log P, and aqueous solubility) of fluoroalkyl-substituted heterocyclic amines were profiled to facilitate the amines' rational application in medicinal chemistry research. The features of fluorine-containing compounds were compared to those of the corresponding parent non-fluorinated heterocycles and the corresponding fluorinated n-alkylamines. Amine basicity was observed to change in a monotonic fashion depending on the fluorination pattern. Although the introduction of fluoroalkyl groups had complex effects on the lipophilicity and aqueous solubility of the compounds, possible contributions of the fluorination pattern, ring size, and conformation of the substituent in the ring were addressed for a series of derivatives. The summarized data provide a useful guideline for the application of fluorinated motifs for fine-tuning a compound's properties related to drug discovery.

Directly Spun Epoxy‐Crosslinked Polyethylenimine Fiber Sorbents for Direct Air Capture and Postcombustion Capture of CO2

A novel, directly‐injected solid fiber sorbent is synthesized from a solvent‐stable, epoxy‐crosslinked basic immobilized amine sorbent (BIAS) for CO2 capture. Leach resistance of the BIAS organics toward 1‐methyl‐2‐pyrrolidone/H2O (90/10, fiber solvent) reaches near 100% at the expense of CO2 capture and is achieved by increasing the extent of crosslinking. The optimized fiber sorbent, prepared with an N,N‐diglycidyl‐4‐glycidyloxyaniline/polyethylenimine (PEI)‐0.35/1 wt. ratio, retains 79.2% of PEI and captures 0.37 (direct air capture [DAC]) and 0.67 (postcombustion) mmol CO2g‐fiber−1. A nonoptimized prototype hollow fiber exhibits a stable 0.2 mmol CO2g‐fiber−1 during DAC cycling and is assembled into a ten‐fiber module. These results demonstrate a large step toward practical application of this material.

Dual Activation of Carboxylic Acid Functionality by Protic Ionic Liquid: Solvent and Metal Free Strategy for Selective Esterification of Alcohols and Acylation of Aromatic Amines

AbstractHighly efficient and chemoselective esterification of alcohols and acylation of aromatic amines with carboxylic acids using imidazolium based protic ionic liquid, 1‐butyl‐imidazolium trifluoroacetate ([HBIm]TFA) as activator has been realized under organic volatile solvent free condition. The protic ionic liquid played dual role for activation of carboxylic acid which was proved by NMR study. A very interesting aspect of the present protocol is the acylation of less basic aromatic amines than the more reactive aliphatic amines as the later one forms salt with carboxylic acid. Our methodology offers several advantages like high yield, fast, efficient, chemo‐selectivity, metal and other coupling agent free procedure, recyclability of ionic liquid used and formation of water as the only by‐product.

Dearomative (3 + 2) Cycloadditions of Unprotected Indoles.

The (3 + 2) cycloaddition of various indoles with a dithioallyl cation affords dearomatized cyclopentannulated adducts, with complete control of regioselectivity and excellent chemo- and diastereoselectivity. The success of the reaction critically relies on the use of an excess of very strong Brønsted acid, which paradoxically prevents carbocationic side reactions. The reaction tolerates sensitive functionalities such as basic amines or free hydroxyls, and we demonstrate its use in late stage derivatization of highly functionalized, unprotected indoles.

ThioCORMates: Tunable and Cost-Effective Carbon Monoxide-Releasing Molecules.

Carbon monoxide-releasing molecules (CORMs) can offer a safer alternative to CO delivery than the use of CO gas cylinders. Upon treatment with an amine base, S-aryl thioformates ("thioCORMates") release CO nearly quantitatively at room temperature, a gas which can then be harnessed for carbonylative cross-coupling, biological study, or inorganic synthesis. These bench-stable molecules are easily synthesized from the corresponding thiophenol and can be electronically tuned to release CO at different rates-from less than 1 min to greater than 1 h-offering a practical alternative to existing CORM technology. Finally, isotopically labeled 13 CO can be conveniently generated and used, with the thioCORMate synthesized from 13 C-formic acid.

Preparation and evaluation of a perylenediimide bridged bis(β-cyclodextrin) chiral stationary phase for HPLC.

A large π-conjugated perylenediimide bridged bis(β-cyclodextrin)-bonded stationary phase (PBCDP) was first prepared and characterized. The chiral HPLC performance was systematically evaluated using a series of chiral probes. The results showed that PBCDP could resolve 36 kinds of chiral compounds in reversed-phase and polar organic modes with high resolutions (Rs) 1.48-3.28 for profens, 1.25-2.85 for triazoles, 1.34-5.29 for flavanones, 1.66-4.58 for amino acids and 1.22-1.97 for β-blockers. Especially, PBCDP could completely resolve acidic non-steroidal chiral drugs (profens) and simultaneously resolve basic five triazole pesticides, which were difficult to separate by ordinary CDCSP. Compared with CDCSP (15 kinds), the new stationary phase has a wider resolution range (36 kinds). Obviously, the synergistic inclusion of the two cavities of bridged cyclodextrin, as well as the large π-π stacking, hydrogen bond, dipole-dipole and basic primary amine site (-NH-) provided by the perylenediimide bridging group contributed together to the improvement of the above chiral separations. PBCDP was a new type of versatile chiral separation material without port derivatization.

Microwave-accelerated regeneration of a non-aqueous slurry for energy-efficient carbon sequestration

We have developed a slurry of basic immobilized amine sorbent (BIAS) and polydimethylsiloxane (PDMS) oil for a CO2 adsorption/desorption process aided by the Microwave-Accelerated Regeneration of a Slurry (MARS). Selective microwave heating of CO2-adsorbed BIAS can accelerate the CO2 desorption flux by 10 times and consume much less energy for sorbent regeneration, compared to thermal heating. Furthermore, the microwave regeneration temperatures of the slurry can be lowered to 65–85 °C. These results indicate that the microwave-accelerated swing method is highly energy-efficient, which can substantially decrease the energy penalty for CO2 capture and downscale the capture process, especially the regeneration equipment. The microwave-assisted non-aqueous capture technology without water and steam use can decrease the cooling duty by 18–48%, compared to the aqueous amine-based capture technology and promote decarbonization in a more sustainable manner.

Hydrophobization of Monolithic Resorcinol-Formaldehyde Xerogels by Means of Silylation.

In materials research, the control of wettability is important for many applications. Since they are typically based on phenolics, organic aerogels, and xerogels are intrinsically hydrophilic in nature, and examples of the chemical functionalization of such gels are scarce and often limited to powders. This study reports on the silylation of monolithic resorcinol-formaldehyde (RF) xerogels using solutions of silyl chlorides and triflates, respectively, in combination with an amine base. The resulting gels are structurally characterized by means of elemental analysis, X-ray photoelectron spectroscopy, pycnometry, sorption analysis, and scanning electron microscopy with electron-dispersive X-ray spectroscopy. The wetting behavior of the silylated gels was studied by the determination of the contact angle to water after exposure of the gels to ambient air. Additionally, the uptake of liquid water and aqueous acids and bases was investigated. As a result, processes for the functionalization of RF xerogels with sterically demanding silyl moieties have been established. Although the analyses indicate that silylation occurred to a rather small extent, highly hydrophobic gels resulted which retained the wetting behavior over the course of several months with contact angles of >130°. Monoliths bearing sterically demanding silyl groups showed higher stability towards aqueous acid than trimethylsilylated RF gels.

An Olefin-based, Fluorescent Covalent Organic Framework for Selective Sensing of Aromatic Amines.

Owing to various chemical structures and different basicity of amines, a fluorescent probe that could distinguish aromatic and aliphatic amines is highly desirable for practical applications. Herein, an olefin-based, fluorescent COF (COF-Py-AN) with unique π-electron deficient groups was synthesized, which was a functionalized platform to realize sensing of π electron-rich aromatic amines. COF-Py-AN displayed fluorescence quenching in the presence of aromatic amines like aniline, with excellent selectivity against a variety of aromatic molecules, and the detection limit of COF-Py-AN toward aniline was as low as 1.29 μM. More importantly, COF-Py-AN could realize discriminating between aromatic and aliphatic amines. Furthermore, density functional theory calculations showed that the photoinduced electron transfer mechanism contributes to fluorescence sensing. This is the first example of olefin-based fluorescent COF materials for selective sensing of aromatic amines.

Nickel-Catalyzed Suzuki–Miyaura Cross-Coupling Facilitated by a Weak Amine Base with Water as a Cosolvent

Nickel-Catalyzed Suzuki–Miyaura Cross-Coupling Facilitated by a Weak Amine Base with Water as a Cosolvent

A thiadiazole-functionalized Zn(II)-based luminescent coordination polymer with seven-fold interweaved herringbone nets showing solvent-responsive fluorescence properties and discriminative detection of ethylenediamine

A benzothiadiazole-functionalized luminescent Zn(II) coordination polymer (CP) {[Zn2(bcpBTD)2(bpBTD)(H2O)2]∙DMF}n (1, H2bcpBTD = bis(4-carboxyphenyl)benzothiadiazole, bpBTD = bis(pyridin-4-yl)benzothiadiazole, DMF = N,N-dimethylformamide) has been successfully constructed. Compound 1 has a two-dimensional (2D) 3-connected (6,3) herringbone net, which is interweaved by other six identical nets in a 7-fold 2D + 2D → 2D interweaved manner. XRPD patterns proved that 1 is highly stable in common solvents, including H2O, acetone, CH3CN, CH2Cl2, N,N-dimethylacetamide (DMAc), DMF, CH3OH, and toluene, and in pH 2–11 aqueous solutions for 5 days. Upon irradiation, 1 emitted green light fluorescence in solid-state and solvent-responsive bright fluorescence in suspension-phase varying from pale-blue light in toluene, CH3CN, CH2Cl2, and acetone to blue-cyan light in CH3OH, DMF and DMAc, and to green light in H2O. In addition, the emission intensity of 1 was greatly enhanced in pH 10 and 11 aqueous solutions but much weaker and less sensitive to other pH values (pH = 4–9, 12, and 13). Of particular note, the H2O suspension of 1 is capable of detection of ethylenediamine (en) through a remarkable fluorescence enhancement (turn-on) response, with excellent sensitivity as low as 0.87 μM (corresponding to 0.052 ppm). The discriminative en detection is properly interpreted by the cooperative effects of absorbance caused enhancement (ACE) and the amine basicity.

Examples Showing the Utility of Doping Experiments in 1H NMR Analysis of Mixtures.

Here we provide examples that demonstrate the value of using properly designed and easily performed doping experiments to give insights about the nature of the analyte(s) present in a 1H NMR sample. Two mixtures, the first quite complex and the second far less so, have been chosen: (i) the crude pyrolysate from reaction of butyric acid in (supercritical) water at 600 °C and (ii) a mixture of two basic amines. In the former, 13 distinct carbonyl-containing compounds, ranging in relative concentration of nearly 2 orders of magnitude, were positively identified. The latter highlights the advantage of using a doping experiment as opposed to merely comparing the spectra from two separate samples containing the same analyte.

Effect of Bis‐Dimethylamine Substitution on DNA Binding Property and Cytotoxic Activity of Polyhydroxyxanthone

AbstractA bis‐dimethylamine substituted xanthone (Xan‐2) was obtained by cationic modification of the free C3 and C6 hydroxy groups of 1,3,6‐trihydroxyxanthone (Xan‐1) which was isolated from Polygala hongkongensis Hemsl.. The results of the spectroscopic analysis, melting profiles, electrophoretic migration, PCR assay and molecular docking indicated that the hydrophobic plane of Xan‐1 and Xan‐2 could intercalate into the DNA base pairs meanwhile the basic amine alkyl chain of Xan‐2 could bind with DNA phosphate framework via electrostatic interaction. Thus, Xan‐2 exhibited higher DNA binding affinity than Xan‐1. Further study showed that Xan‐2 could inhibit the proliferation of HeLa, SGC‐7901 and A549 cells effectively by MTT assay and induce apoptosis of HeLa cells as detected by AO/EB staining and flow cytometry assay. Interestingly, Xan‐2 exhibited selective cytotoxicity to cells, which was proved by its relatively low inhibitory effect on Raw 264.7 cell. What these studies mean is that disubstituted amine alkyl chains will play an important role in DNA binding property and cytotoxic activity, providing a direction for the development of novel potential antitumor agents.

Allylic C-H amination cross-coupling furnishes tertiary amines by electrophilic metal catalysis.

Intermolecular cross-coupling of terminal olefins with secondary amines to form complex tertiary amines-a common motif in pharmaceuticals-remains a major challenge in chemical synthesis. Basic amine nucleophiles in nondirected, electrophilic metal-catalyzed aminations tend to bind to and thereby inhibit metal catalysts. We reasoned that an autoregulatory mechanism coupling the release of amine nucleophiles with catalyst turnover could enable functionalization without inhibiting metal-mediated heterolytic carbon-hydrogen cleavage. Here, we report a palladium(II)-catalyzed allylic carbon-hydrogen amination cross-coupling using this strategy, featuring 48 cyclic and acyclic secondary amines (10 pharmaceutically relevant cores) and 34 terminal olefins (bearing electrophilic functionality) to furnish 81 tertiary allylic amines, including 12 drug compounds and 10 complex drug derivatives, with excellent regio- and stereoselectivity (>20:1 linear:branched, >20:1 E:Z).