Synthesis of quaternary ammonium salts based on quinuclidin-3-ol and pyridine-4-aldoxime with alkyl chains

Aim: In search of a new class of potential antimicrobial agents, novel ammonium salts based on quinuclidine-3-ol and pyridine-4-aldoxime with different lengths of alkyl chains were synthesized and analyzed. In addition to their potential biological application, newly synthesized salts containing terminal bromine could possibly be used for the synthesis of more potent bisquaternary salts. Methods: The commercially available quinuclidine-3-ol and pyridine-4-aldoxime were used for the synthesis of new derivatives with the appropriate alkyl chains. The purity of the synthesized salts was tested by thin-layer chromatography on an aluminum plate where aluminum oxide was used as a stationary phase. Melting points were determined in open capillaries using an instrument for melting point determination and the obtained values were left uncorrected. The FTIR spectra were recorded with a spectrometer and the data were analyzed in cm-1. Results: All the synthesized compounds, which contained heterocyclic moiety and alkyl chains (with or without a terminal bromine atom), were obtained in very good yields under the simple quaternization conditions. The better product yields were observed in reactions with quinuclidine3-ol (46-95%) compared to those with pyridine-4-aldoxime (49-59%). The obtained products were analyzed and confirmed by the thin-layer chromatography, the melting point measurement and the FTIR spectra. Conclusion: The observed difference in product yields could be explained by the different basicity of the nitrogen atom of quinuclidin-3-ol than that of pyridine-4-aldoxime. All prepared salts have a positively charged nitrogen atom as a part of their polar “head” and a long hydrocarbon chain as the non-polar “tail”. Such a structure allows electrostatic interaction with the negatively charged bacterial membrane and causes it to be disrupted. The structure of the prepared salts containing long alkyl chains could be crucial for their antimicrobial activity

Biological activity of monoquaternary ammonium compounds based on 3-substituted quinuclidine: A short review

Quaternary ammonium compounds (QACs) have a long-known application as antiseptics and disinfectants applied in various industries such as pharmaceutical, agricultural and food industry. Given the alarming number of QACs resistant bacteria, there is an urgent need to develop new QACs with broad-spectrum antimicrobial activities and low tendency to trigger bacterial resistance. One recently proposed approach to develop new QACs is based on quaternization of natural products, which proved to be successful. Quinuclidine is an interesting natural precursor find to be a part of the structure of biologically active cinchona alkaloids. In addition to the well-established medicinal and pharmaceutical potential of 3-substituted quinuclidines, QACs based on 3-substituted quinuclidines, have only recently been shown to exhibit a significant antimicrobial activity. Most importantly, these compounds exhibit low toxicity toward normal human cell lines, which opens up a new chapter in the QACs field ensuring further investigation of possible therapeutic application of 3-substituted quinuclidine based QACs.</p

Euler-Stieltjes constants for the Rankin-Selberg L-function and weighted Selberg orthogonality

Let E be Galois extension of Q of finite degree and let π and π\u27 be two irreducible automorphic unitary cuspidal representations of GLm(EA) and GLm\u27(EA), respectively. We prove an asymptotic formula for computation of coefficients γπ,π\u27(k) in the Laurent (Taylor) series expansion around s=1 of the logarithmic derivative of the Rankin-Selberg L-function L(s, π × π\u27) under assumption that at least one of representations π, π\u27 is self-contragredient and show that coefficients γπ,π\u27(k) are related to weighted Selberg orthogonality. We also replace the assumption that at least one of representations π and π\u27 is self-contragredient by a weaker one

3-Amidoquinuclidine Derivatives: Synthesis and Interaction with Butyrylcholinesterase

Racemates as well as (R)- and (S)-enantiomers of 3-pivalamidoquinuclidine (PivQ) and 3-acetamidoquinuclidine (AcQ) were prepared. Their quaternary racemic and enantiomerically pure N-benzyl derivatives (BnlPivQ and BnlAcQ) were synthesized as well. The amides were tested as substrates and inhibitors of butyrylcholinesterase (BChE) from horse serum (EC 3.1.1.8). No hydrolysis was observed under the experimental conditions applied. On the contrary, inhibition of BChE by (R)- and (S)-enantiomers of N-benzylquinuclidinium amides of pivalic acid was observed. The (S)-BnlPivQ with Ki = 41.57 µmol dm–3 was 3-fold more potent inhibitor than the (R)-enantiomer. On the other hand, preliminary results indicated that both enantiomers of N-benzylquinuclidinum amides of acetic acid may possibly be inhibitors as well as activators depending on the concentrations of benzoylcholine (BzCh) used as a substrate of BChE

High-order harmonic generation by polyatomic molecules

We present a theory of high-order harmonic generation by arbitrary polyatomic molecules based on the molecular strong-field approximation (MSFA) in the framework of the S-matrix theory. A polyatomic molecule is modeled by an (N + 1)-particle system, which consists of N heavy atomic (ionic) centers and an electron. We derived various versions (with or without the dressing of the initial and/or final molecular state) of the MSFA. The general expression for the T-matrix element takes a simple form for neutral polyatomic molecules. We show the existence of the interference minima in the harmonic spectrum and explain these minima as a multiple-slit type of interference. This is illustrated by numerical examples for the nitrous oxide (N2O) molecule exposed to strong linearly polarized laser field

3-Amidoquinuclidine Derivatives: Synthesis and Interaction with Butyrylcholinesterase

Racemates as well as (R)- and (S)-enantiomers of 3-pivalamidoquinuclidine (PivQ) and 3-acetamidoquinuclidine (AcQ) were prepared. Their quaternary racemic and enantiomerically pure N-benzyl derivatives (BnlPivQ and BnlAcQ) were synthesized as well. The amides were tested as substrates and inhibitors of butyrylcholinesterase (BChE) from horse serum (EC 3.1.1.8). No hydrolysis was observed under the experimental conditions applied. On the contrary, inhibition of BChE by (R)- and (S)-enantiomers of N-benzylquinuclidinium amides of pivalic acid was observed. The (S)-BnlPivQ with Ki = 41.57 µmol dm–3 was 3-fold more potent inhibitor than the (R)-enantiomer. On the other hand, preliminary results indicated that both enantiomers of N-benzylquinuclidinum amides of acetic acid may possibly be inhibitors as well as activators depending on the concentrations of benzoylcholine (BzCh) used as a substrate of BChE

On a class of periodic Dirichlet series with functional equation

The structure of the extended Selberg class of degree one was completely revealed by Kaczorowski and Perelli [10]. In this short paper, we give a new characterization of the functions with periodic coefficients in that class by giving a simple relation that the coefficients have to satisfy

On a class of periodic Dirichlet series with functional equation

The structure of the extended Selberg class of degree one was completely revealed by Kaczorowski and Perelli [10]. In this short paper, we give a new characterization of the functions with periodic coefficients in that class by giving a simple relation that the coefficients have to satisfy