Guanidine Research Articles

Orthoamide und Iminiumsalze, C. Vinyloge Guanidiniumsalz-basierte ionische Flüssigkeiten sowie phenyloge Guanidiniumsalze und Orthoamide

Abstract Cyclopropylacetylene and N,N,N′,N′,N′′,N′′-hexamethylguanidinium chloride (1a) react to give the orthoamide derivative 8c, in the presence of sodium hydride. 8c is transformed by elemental iodine to the vinylogous guanidinium salt 6f. Anion metathesis with the salts 5a, 5e, 6g delivers vinylogous guanidinium salts 5e–5i, 12a with counter ions derived from carbon acids (tricyanomethane, 1,1,3,3-tetracyano-propene). Phenylogous amidinium salts 15 guanidinium salts 19, 21 and the phenylogous orthoamide derivatives of formic acid 18 and carbonic acid 33 have been prepared.

Orthoamide und Iminiumsalze, IC. Synthese und Reaktionen von N,N,N′,N′,N′′-Pentaalkyl-N′′-[2-(N,N,N′,N′,N′′-pentaalkylguanidinio)ethyl]-guanidiniumsalzen

Abstract Bis[bis(dibutylamino)methylen]hydrazine 8 is prepared from N,N,N′,N′-tetrabutylchloroformamidinium chloride (4c) and hydrazine. Bromine transforms 8 to the heterocyclic guanidinium salt 15a which is isolated as tetraphenylborate. From N,N,N′,N′-tetraalkylchloroformamidiniumchlorides and ethylendiamine the diguanidines are prepared which are alkylated to give diguanidinium salts, From these salts guanidinium salts can be prepared by anion metathesis with tetraphenylborate-, iodide-, hexafluorphosphate-, trifluoromethansulfonat-, bis(trifluormethansulfonyl)imide and tricyanmethanide as counteranions. The structure of the compounds 15 and 17b is confirmed by crystal structure analyses.

Orthoamide und Iminiumsalze, IIC. Darstellung von N-(ω-Ammonioalkyl)-N,N′,N′,N″,N″-peralkylierten Guanidiniumsalzen und N-(ω-Aminoalkyl)-N′,N′,N″,N″-tetramethylguanidinen

Abstract N,N,N′,N′-Tetraalkylchlorformamidiniumchlorides 1a, b react with ω-dimethylaminoalkylamines 19, 20 to give mixtures of N-(ω-dimethylammonioalkyl)-guanidinium salts 12, 13 and N-(ω-dimethylaminoalkyl)-guanidinium salts 21, 22. These mixtures are transformed to mixtures of the ureas 15, 17 and N-(ω-dimethylaminoalkyl)-guanidines 23, 25 on treatment with aqueous sodium hydroxide. The reaction of N-(3-dimethylammoniopropyl)-guanidin 25a with dimethylsulfate in a molar ratio of 1:1 delivers a mixture of the N-(3-dimethylaminopropyl)-N,N,N′,N′,N″,N″-pentamethyl-guanidinium salt 29a and the N-(3-dimethylammoniopropyl)-N,N′,N′,N″,N″-pentamethyl-guanidinium-bis (methylsulfate) 33a. The action of dimethylsulfate on the guanidines 23a, 25a in a molar ratio of 2:1 affords the bisquarternary salts 32a, 33a. Alkylating reagents as methyliodide, benzylbromide, allylbromide and chloroacetonitrile attack N-(2-dimethylaminoethyl)-N′,N′,N″,N″-tetraethylguanidine (23b) in a molar ratio of 1:1 cleanly at the dimethylaminoethylgroup to give the ammonium salts 30a–d. As a strong base the guanidine 23b dehydrochlorinates β-Chlorpropionitrile and chloroacetone under formation of the guanidinium salt 21c. In contrast to this the reaction of ethyl bromoacetate with the N-(2-dimethylaminoethyl)guanidine 23b occurs at the guanidinogroup giving the guanidinium salt 28c. The methylation of the guanidinium chlorides 21a, 22a with dimethyl sulfate affords the bis-quaternary salts 35b, 36b with mixed anions. From the heterocyclic guanidines 14, 16 and the alkylating reagents benzylbromide and ethyl bromoacetate the heterocyclic guanidinium salts 37a, b, 39a, b can be obtained. The reactions with ethyl chloroformiate proceed in an analogous way giving the guanidinium salts 37c, 39c. The N-alkyl-N,N,N′,N′-tetramethyl-(3-ureidopropyl)guanidinium salts 41a, b can be prepared from the N′,N′,N″,N″-tetramethyl-N′′-(3-ureidopropyl) guanidine 17a and the alkylating compounds dimethyl sulfate and benzyl bromide. Several compounds obtained that way were transformed to the corresponding tetraphenyloborates and bis(tetraphenylborates), respectively.

An effective method for preparation of high purity oligohexamethylene guanidine salts

Objectives. Given that microorganisms can become resistant to certain groups of drugs and considering also their ability to form biofilms, the development of new drugs that are active against adapted microflora is required. This study focused on the development of a new method for the synthesis of a promising compound, the branched hydrosuccinate oligohexamethylene guanidine (OHMGsucc), with high purity that meets the standards of the 14th edition State Pharmacopeia of the Russian Federation (SPRF). Previously proposed methods have managed to isolate this product, which, however, complies with the requirements of the outdated SPRF. Therefore, the main aim of this study was to update the regulatory framework for the indicated OHMG salt for its further use in the pharmaceutical industry according to modern standards.Methods. To control the residual impurities of hexamethylenediamine (HMDA) and guanidine hydrochloride (GHC), high-performance liquid chromatography (HPLC) was applied using a Thermo Scientific Dionex UltiMate 3000 chromatograph, and the chromatographic signals of the test solution with those of a standard sample solution obtained by a previously published conventional method were compared.Results. The HPLC experimental data indicated a significant difference in the quantitative content of HMDA and GHC observed for the new and older preparation method of the branched OHMGsucc, suggesting that the method disclosed in this article can be used to obtain highly pure OHMGsucc.Conclusions. The specified compound was standardized with the parameter “related impurities” according to the current (14th) edition of the SPRF. The effectiveness and reproducibility of the proposed method was experimentally confirmed. In addition, a process diagram for the preparation of the indicated OHMG salt was prepared.

Xiaohua Liu.

"In a spare hour, I walk my dog … My favorite time of day is when I enjoy my walks in the garden…" Find out more about Xiaohua Liu in her Author Profile.

Enzymatic and Chemical-Based Methods to Inactivate Endogenous Blood Ribonucleases for Nucleic Acid Diagnostics

There are ongoing research efforts into simple and low-cost point-of-care nucleic acid amplification tests (NATs) addressing widespread diagnostic needs in resource-limited clinical settings. Nucleic acid testing for RNA targets in blood specimens typically requires sample preparation that inactivates robust blood ribonucleases (RNases) that can rapidly degrade exogenous RNA. Most NATs rely on decades-old methods that lyse pathogens and inactivate RNases with high concentrations of guanidinium salts. Herein, we investigate alternatives to standard guanidinium-based methods for RNase inactivation using an activity assay with an RNA substrate that fluoresces when cleaved. The effects of proteinase K, nonionic surfactants, SDS, dithiothreitol, and other additives on RNase activity in human serum are reported. Although proteinase K has been widely used in protocols for nuclease inactivation, it was found that high concentrations of proteinase K are unable to eliminate RNase activity in serum, unless used in concert with denaturing concentrations of SDS. It was observed that SDS must be combined with proteinase K, dithiothreitol, or both for irreversible and complete RNase inactivation in serum. This work provides an alternative chemistry for inactivating endogenous RNases for use in simple, low-cost point-of-care NATs for blood-borne pathogens.

Experimental and calculated second harmonic generation of a guanidinium salt in the solid state

A new salt containing both dipolar and octupolar molecules has been synthesized and its structural features fully revealed, namely, its noncentrosymmetry. The microscopic optical properties of a neutral cluster were calculated probing several functionals; a better performance was observed for functionals with high percentage of Hartree-Fock exchange. The vector and septor irreducible components, for individual ions, were also calculated in order to evaluate their ratio and the dipolar/octupolar character. The optical properties of the solid state were computed, using the oriented gas model and two different local field factors. For the SHG generation, the calculated value compares well with the experimental value measured for the powder form, of the order of magnitude of the urea signal.

Laboratory testing of SARS-CoV, MERS-CoV, and SARS-CoV-2 (2019-nCoV): Current status, challenges, and countermeasures.

SummaryEmerging and reemerging infectious diseases are global public concerns. With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus, SARS‐CoV‐2 has been attracting tremendous attention. Rapid and accurate laboratory testing of SARS‐CoV‐2 is essential for early discovery, early reporting, early quarantine, early treatment, and cutting off epidemic transmission. The genome structure, transmission, and pathogenesis of SARS‐CoV‐2 are basically similar to SARS‐CoV and MERS‐CoV, the other two beta‐CoVs of medical importance. During the SARS‐CoV and MERS‐CoV epidemics, a variety of molecular and serological diagnostic assays were established and should be referred to for SARS‐CoV‐2. In this review, by summarizing the articles and guidelines about specimen collection, nucleic acid tests (NAT) and serological tests for SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2, several suggestions are put forward to improve the laboratory testing of SARS‐CoV‐2. In summary, for NAT: collecting stool and blood samples at later periods of illness to improve the positive rate if lower respiratory tract specimens are unavailable; increasing template volume to raise the sensitivity of detection; putting samples in reagents containing guanidine salt to inactivate virus as well as protect RNA; setting proper positive, negative and inhibition controls to ensure high‐quality results; simultaneously amplifying human RNase P gene to avoid false‐negative results. For antibody test, diverse assays targeting different antigens, and collecting paired samples are needed.

A 1D Helical Chain Heterpolyniobate Templated by AsO33.

A novel polyoxoniobate cluster directed by AsO33-, {[Cu(phen)]5[Nb6O19][As2Nb6O22]}2 (1a), has been successfully synthesized by a "two-pot" strategy, namely, the conventional aqueous solution and diffusional methods. It incorporates two {[Cu(phen)]2Nb6O19} and two {[Cu(phen)]3As2Nb6O22} subunits. Surprisingly, by changing the reaction conditions, one of the subunits {[Cu(phen)]2Nb6O19} was isolated as a guanidinium salt. These architectures were structurally characterized by single crystal X-ray diffraction, TGA, IR, elemental analysis and PXRD, etc. Furthermore, the behavior of 1 in aqueous solution was measured by electrospray ionization mass spectrometry, and the magnetic property in the low temperature range indicates the presence of antiferromagnetic interactions.

Valacyclovir toxicity in peritoneal dialysis

Valacyclovir (Prodrug) an antiviral agent is not well cleared by peritoneal dialysis and can cause neuropsychiatric manifestations in patient with renal failure on peritoneal dialysis and having Herpes Zoster infection being treated with this drug. Methodology followed for the collection of data and literature review was by using a medline search using the terms Acyclovir, nervous system effects, Valacyclovir, neurotoxicity and peritoneal dialysis. The representative case discussed is about an elderly gentleman with chronic renal failure on CCPD presenting with hallucinations, altered sensorium and restlessness following treatment with Valacyclovir 1000 mg three times per oral daily who was admitted and evaluated. It is of vital importance to consider the differential diagnosis of Herpes zoster encephalitis in the differential diagnosis of these patients as it is difficult to rule it out. The mechanism of this drug induced neurotoxicity is thought to be probably, the accumulation of serum carboxymethoxymethyl guanidine (CMMG), a toxic metabolite of valacyclovir.As peritoneal dialysis is not very effective in removal of this drug, it is thought to be beneficial to change to Hemodialysis for short duration so as to clear the drug from the system as shown in the case and in the discussion. Safe doses in peritoneal dialysis are not clearly delineated. Extreme precaution must be exercised while prescribing these group of anti-viral drugs in patients with CKD and especially those on peritoneal dialysis. If such a patient does manifest neuropsychiatric symptoms it is necessary to immediately stop the drug concerned. Methods to increase the excretion of the drug must be employed immediately or to remove it by intensification of PD or ideally to aggressively remove it by means of hemodialysis. Moreover there is a paucity of similar reports in the literature.

A series of guanidine salts of 3,6-bis-nitroguanyl-1,2,4,5-tetrazine: green nitrogen-rich gas-generating agent.

Nitrogen-rich energetic materials (EMs) have been widely studied because of their high thermal stability, insensitivity, excellent detonation performance and non-toxic characteristics. In particular, these compounds are well applied as gas-generating agents (GGAs). As a nitrogen-rich heterocyclic framework, 1,2,4,5-tetrazine derivatives have shown great potential in the design of GGAs. The guanidine salts of 3,6-bis-nitroguanyl-1,2,4,5-tetrazine (DNGTz), guanidine (G2DNGTz) (1), aminoguanidine (AG2DNGTz) (2), diaminoguanidine (DAG2DNGTz) (3), and triaminoguanidine (TAG2DNGTz) (4) have been synthesized and characterized by elemental analysis and FT-IR. The crystal structures of 1 and 2 were obtained by X-ray single crystal diffraction. Crystal analysis shows that 1 and 2 arrange through zigzag-chain-like assembly and face-to-face geometries, which is helpful in decreasing mechanical sensitivity. The thermal stability and thermal decomposition kinetics of these four salts were studied by Differential Scanning Calorimetry (DSC). Furthermore, the thermogravimetry-Fourier transform infrared-mass spectrometry (TG-FTIR-MS) analysis of thermal decomposition products reveals that the main decomposition gaseous products are H2O, N2O, CO2, NO, N2 and NH3. Then, the cytotoxicity of the four salts was tested by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) method, and it was found that salts 1–4 show slight cytotoxicity in mouse fibroblasts (L929), at a concentration of 0.125 mg ml−1. The insensitivity, low toxicity, and production of clean gases without solid residue after burning of salt 1 indicate that it can be used as a potential green energetic material for GGAs.

One-Pot Absolute Stereochemical Identification of Alcohols via Guanidinium Sulfate Crystallization.

A novel technique for the absolute stereochemical determination of alcohols has been developed that uses crystallization of guanidinium salts of organosulfates. The simple one-pot, two-step process leverages facile formation of guandinium organosulfate single crystals for the straightforward determination of the absolute stereochemistry of enantiopure alcohols by means of X-ray crystallography. The strong hydrogen bonding network drives the stability of the crystal lattice and allows for a diverse range of organic alcohol substrates to be analyzed.

Spectral determination of novel methacryloyl guanidine compounds in water solutions

For production and application of novel biocidal guanidine polymer compounds techniques for monitoring the toxic monomer and oligomer components in polymer aqueous solutions are required. A direct spectroscopic method is offered for determination of methacryloyl guanidine salts, polymer and copolymer in water solutions at native pH. The impact of unsubstituted guanidine and methacrylate guanidine contaminants is also discussed. The spectroscopic method offered is simple, rapid and effective for monitoring contamination of polymethacryloylguanidines with toxic monomer components during synthesis of polymers and copolymers from different monomer salts, during dialysis and other manufacturing stages of biocidal polymers.

Self-Assembly Supramolecular Systems Based on Guanidinium Salts Modified Hyperbranched Polyamidoamine and Cationic Acrylamide Copolymers.

Herein, novel hyperbranched polyamidoamine guanidinium salts (GS-h-PAMAM) and two cationic acrylamide copolymers P(AM-DAC-ABSM) and P(AM-DAC-AMTU) were successfully prepared. Then, self-assembly supramolecular systems were synthesized by directly mixing GS-h-PAMAM with copolymers in aqueous solution, and the mechanism of the self-assembly process was speculated. FT-IR, NMR, and SEM were used for structural confirmation. Furthermore, the excellent solution properties revealed that the supramolecular systems had potential application in clay hydration inhibitors. More importantly, utilizing functionalized hyperbranched polyamidoamine in the synthesis self-assembly supramolecular systems was an effective strategy for expanding their application fields and developing new functional materials, providing a powerful reference for the next study.

Efficient Catalysts of Acyclic Guanidinium Iodide for the Synthesis of Cyclic Carbonates from Carbon Dioxide and Epoxides under Mild Conditions

We have studied the synthesis of five-membered cyclic carbonates through the cycloaddition of CO2 to epoxides by using acyclic guanidinium salts. We have found that the cycloaddition reactions proceed smoothly at ordinary temperatures and pressures and result in good yields when acyclic guanidinium iodides are employed as catalysts. Both cation moiety and anion moiety of the guanidinium salts play important roles in their catalytic activity. It is essential to have active hydrogens on the cation moiety as well as an iodide ion as the anion moiety so as to achieve good catalytic activity. Guanidinium iodides with three or more active hydrogens give cyclic carbonates in high yields in polar solvents such as 1-methylpyrrolidin-2-one, whereas the guanidinium iodides with one or two active hydrogens show good catalytic activity in less polar solvents such as 2-methyltetrahydrofuran.

Guanidinium-Functionalized Photodynamic Antibacterial Oligo(Thiophene)s

ABSTRACTWe synthesized precision oligomers of thiophene with cationic and hydrophobic side chains to mimic the charge, hydrophobicity, and molecular size of antibacterial host defense peptides (HDPs). In this study, the source of cationic charge was a guanidinium salt moiety intended to reflect the structure of arginine-rich HDPs. Due to the pi-conjugated oligo(thiophene) backbone structure, these compounds absorb visible light in aqueous solution and react with dissolved oxygen to produce highly biocidal reactive oxygen species (ROS). Thus, the compounds exert bactericidal activity in the dark with dramatically enhanced potency upon visible light illumination. We find that guanylation of primary amine groups enhanced the activity of the oligomers in the dark but also mitigated their light-induced activity enhancement. In addition, we also quantified their toxicity to mammalian cell membranes using a hemolysis assay with red blood cells, in the light and dark conditions.

Comparative Theoretical Studies on a Series of Novel Energetic Salts Composed of 4,8-Dihydrodifurazano[3,4-b,e]pyrazine-based Anions and Ammonium-based Cations.

4,8-Dihydrodifurazano[3,4-b,e]pyrazine (DFP) is one kind of parent compound for the synthesis of various promising difurazanopyrazine derivatives. In this paper, eleven series of energetic salts composed of 4,8-dihydrodifurazano[3,4-b,e]pyrazine-based anions and ammonium-based cations were designed. Their densities, heats of formation, energetic properties, impact sensitivity, and thermodynamics of formation were studied and compared based on density functional theory and volume-based thermodynamics method. Results show that ammonium and hydroxylammonium salts exhibit higher densities and more excellent detonation performance than guanidinium and triaminoguanidinium salts. Therein, the substitution with electron-withdrawing groups (–NO2, –CH2NF2, –CH2ONO2, –C(NO2)3, –CH2N3) contributes to enhancing the densities, heats of formation, and detonation properties of the title salts, and the substitution of –C(NO2)3 features the best performance. Incorporating N–O oxidation bond to difurazano[3,4-b,e]pyrazine anion gives a rise to the detonation performance of the title salts, while increasing their impact sensitivity meanwhile. Importantly, triaminoguanidinium 4,8-dihydrodifurazano[3,4-b,e]pyrazine (J4) has been successfully synthesized. The experimentally determined density and H50 value of J4 are 1.602 g/cm3 and higher than 112 cm, which are consistent with theoretical values, supporting the reliability of calculation methods. J4 proves to be a thermally stable and energetic explosive with decomposition peak temperature of 216.7 °C, detonation velocity 7732 m/s, and detonation pressure 25.42 GPa, respectively. These results confirm that the derivative work in furazanopyrazine compounds is an effective strategy to design and screen out potential candidates for high-performance energetic salts.

Nitrogen‐rich Salts based on 3‐Dinitromethyl‐[1,2,4]triazine: Synthesis, Characterization, and Performance

1,1‐Diamino‐2,2‐dinitroethylene (FOX‐7), one of the most well‐known energetic materials, has attracted broad attention around the world. To extend the chemistry of FOX‐7, we present here a series of energetic salts based on 3‐dinitromethyl‐[1,2,4]triazine, which is prepared from FOX‐7. All these salts were fully characterized using 1H NMR, 13C NMR, IR, and elemental analysis. In addition, the potassium salt (2), ammonium salt (5), and guanidinium salt (7) were further confirmed by single‐crystal X‐ray diffraction. Extensive hydrogen bonds were observed in these salts. The salts exhibit moderate densities varying from 1.63 to 1.76 g·cm–3. All the compounds possess good thermal stability with decomposition temperatures from 118 to 267 °C. The detonation performance for salts were calculated by using EXPLO 5, their detonation velocities are in the range from 6807 to 8614 m·s–1 and detonation pressures fall between 18.8 to 31.6 GPa. All the salts exhibit very low mechanical sensitivity, which indicates their potential application as insensitive energetic materials.

Preparation of Antimicrobial Nanofiltration Membrane via Self-polymerization of Dopamine and Surface Grafting of PHGH

A novel antimicrobial nanofiltration membrane was fabricated by the self-polymerization of dopamine on polysulfone membrane surface and following surface grafting of polyhexamethylene guanidine hydrochloride ( PHGH) in aqueous conditions. The membrane structures, morphologies and hydrophilicity were characterized by attenuated total reflectance-Fourier transform infrared spectroscopy ( ATR-FTIR), scanning electron microscopy ( SEM) and water contact angle measurement. The concentration of PHGH on grafting degree and filtration performance were investigated. Furthermore, the antibacterial performance of composite membranes was evaluated. The results showed that an active layer with nanofiltration performance was formed on polysulfone membrane surface and the hydrophilicity of membranes was significantly improved by the introduction of dopamine and PHGH. The fluxes decreased while the rejections of inorganic salts and dyes increased with the increasing concentration of PHGH. The composite membranes after grafting exhibited excellent antibacterial performance, when mass fraction of PHGH was 3%, the antibacterial rate reached up to 98.5%.

Halide Versus Nonhalide Salts: The Effects of Guanidinium Salts on the Structural, Morphological, and Photovoltaic Performances of Perovskite Solar Cells

The impacts of halide and nonhalide sources of guanidinium cations, including guanidinium chloride (GCl) ((NH2)3CCl) and guanidinium thiocyanate (GTC) ((NH2)3CSCN), are comparatively analyzed on the structural, morphological, and photophysical properties of (CsMAFA)PbBrxI3 − x (x = 0.17) (MA = methylammonium, FA = formamidinium) perovskite films. X‐ray diffraction (XRD) reveals that the formation of photoinactive phases depends on the nature of counterions (halide vs nonhalide). Furthermore, morphological analysis shows that with the addition of guanidinium salts, the apparent grain size decreases due to the enhancement of nucleation density and/or slow growth of perovskite structures. More importantly, the introduction of GCl leads to the fabrication of perovskite solar cells (PSCs), yielding a photovoltage as high as 1.16 V (1.1 V for reference). In contrast, the introduction of GTC minimally affects the photovoltage, underlining the significance of counterions in improving the photovoltage of PSCs. The present preliminary results of the density functional theory based theoretical investigation related to the effect of G cation on the structure of the perovskite system is presented. In summary, the insights gained through structural and morphological characterization helps to understand the critical role of counterions of guanidinium salts in PSCs.