Guanidinium Group Research Articles

Acylguanidine derivatives of zanamivir and oseltamivir: Potential orally available prodrugs against influenza viruses

Zanamivir (ZA) and guanidino-oseltamivir carboxylic acid (GOC) are very potent inhibitors against influenza neuraminidase (NA). The guanidinium moiety plays an important role in NA binding; however, its polar cationic nature also hinders the use of ZA and GOC from oral administration. In this study, we investigated the use of ZA and GOC acylguanidine derivatives as possible orally available prodrugs. The acylguanidine derivatives were prepared by coupling with either n-octanoic acid or (S)-naproxen. The lipophilic acyl substituents were verified to improve cell permeability, and may also improve the bioavailability of acylguanidine compounds. In comparison, the acylguanidines bearing linear octanoyl chain showed better NA inhibitory activity and higher hydrolysis rate than the corresponding derivatives having bulky branched naproxen moiety. Our molecular docking experiments revealed that the straight octanoyl chain could extend to the 150-cavity and 430-cavity of NA to gain extra hydrophobic interactions. Mice receiving the ZA octanoylguanidine derivative survived from influenza infection better than those treated with ZA, whereas the GOC octanoylguanidine derivative could be orally administrated to treat mice with efficacy equal to oseltamivir. Our present study demonstrates that incorporation of appropriate lipophilic acyl substituents to the polar guanidine group of ZA and GOC is a feasible approach to develop oral drugs for influenza therapy.

Arginine-Containing Surfactant-Like Peptides: Interaction with Lipid Membranes and Antimicrobial Activity.

The activity of antimicrobial peptides stems from their interaction with bacterial membranes, which are disrupted according to a number of proposed mechanisms. Here, we investigate the interaction of a model antimicrobial peptide that contains a single arginine residue with vesicles containing model lipid membranes. The surfactant-like peptide Ala6-Arg (A6R) is studied in the form where both termini are capped (CONH-A6R-NH2, capA6R) or uncapped (NH2-A6R-OH, A6R). Lipid membranes are selected to correspond to model anionic membranes (POPE/POPG) resembling those in bacteria or model zwitterionic membranes (POPC/DOPC) similar to those found in mammalian cells. Viable antimicrobial agents should show activity against anionic membranes but not zwitterionic membranes. We find, using small-angle X-ray scattering (SAXS) and cryogenic-TEM (transmission electron microscopy) that, uniquely, capA6R causes structuring of anionic membranes due to the incorporation of the peptide in the lipid bilayer with peptide β-sheet conformation revealed by circular dichroism spectroscopy (CD). There is a preferential interaction of the peptide with POPG (which is the only anionic lipid in the systems studied) due to electrostatic interactions and bidentate hydrogen bonding between arginine guanidinium and lipid phosphate groups. At a certain composition, this peptide leads to the remarkable tubulation of zwitterionic phosphatidylcholine (PC) vesicles, which is ascribed to the interaction of the peptide with the outer lipid membrane, which occurs without penetration into the membrane. In contrast, peptide A6R has a minimal influence on the anionic lipid membranes (and no β-sheet peptide structure is observed) but causes thinning (lamellar decorrelation) of zwitterionic membranes. We also investigated the cytotoxicity (to fibroblasts) and antimicrobial activity of these two peptides against model Gram positive and Gram negative bacteria. A strong selective antimicrobial activity against Gram positive Listeria monocytogenes, which is an important food-borne pathogen, is observed for capA6R. Peptide A6R is active against all three studied bacteria. The activity of the peptides against bacteria and mammalian cells is related to the specific interactions uncovered through our SAXS, cryo-TEM, and CD measurements. Our results highlight the exquisite sensitivity to the charge distribution in these designed peptides and its effect on the interaction with lipid membranes bearing different charges, and ultimately on antimicrobial activity.

KB343, a Cyclic Tris-guanidine Alkaloid from Palauan Zoantharian Epizoanthus illoricatus.

A new tris-guanidine alkaloid, KB343 (1), was isolated from the aqueous extract of a Palauan zoantharian, Epizoanthus illoricatus. The structure of 1 was determined on the basis of spectral analyses of 1 and its derivatives. The absolute configuration for 1 was determined upon comparison of the CD spectrum of 1 to those obtained from density functional theory calculations. The structure of 1 is highly unusual, as three guanidine groups are present in one ring system.

Asymmetric Synthesis of Silanediol Inhibitors for the Serine Protease Coagulation Cascade Enzyme FXIa.

Silanediol peptidomimetics have been prepared, designed to inhibit the serine protease enzyme Factor XIa (FXIa) for treatment of thrombosis without complete interruption of normal hemostasis. These Arg-[Si]-Ala analogues of the FXIa substrate (FIX) are the first silanediol dipeptide analogues to carry a basic guanidine group. Control of stereochemistry was accomplished using catalytic asymmetric hydrosilylation and addition of a silyllithium intermediate to the Davis-Ellman sulfinimine.

Guanidine Substitutions in Naphthyl Systems to Allow a Controlled Excited-State Intermolecular Proton Transfer: Tuning Photophysical Properties in Aqueous Solution

The excited-state intermolecular proton transfer process (ESPT) in aqueous solution is achieved and controlled by the incorporation of guanidine groups in a fluorescent structure. The bisguanidine under investigation exhibits a dual fluorescence emission with a very high Stokes shifts in water, ≈86 (7890) and 210 (14 500) nm (cm–1), and an excited-stated deprotonation coupled to an intramolecular charge transfer (ICT) process contributes to this emission. The study demonstrates that the emission properties of the different protonation states are strongly dependent on the solvent environment, which also allows luminescence of the molecule to be tuned. The results of this work show the potential utility of guanidine substitution for the stabilization of ESPT–ICT processes in water and allow the subsequent logical design of new stimulus-responsive fluorophores.

Importance of Post-translational Modifications in the Interaction of Proteins with Mineral Surfaces: The Case of Arginine Methylation and Silica surfaces.

Understanding the mechanisms involved in the interaction of proteins with inorganic surfaces is of major interest for both basic research and practical applications involving nanotechnology. From the list of cellular proteins with the highest affinity for silica nanoparticles, we highlighted the group of proteins containing arginine-glycine-glycine (RGG) motifs. Biochemical experiments confirmed that RGG motifs interact strongly with the silica surfaces. The affinity of these motifs is further increased when the R residue is asymmetrically, but not symmetrically, dimethylated. Molecular dynamics simulations show that the asymmetrical dimethylation generates an electrostatic asymmetry in the guanidinium group of the R residue, orientating and stabilizing it on the silica surface. The RGG motifs (methylated or not) systematically target the siloxide groups on the silica surface through an ionic interaction, immediately strengthened by hydrogen bonds with proximal silanol and siloxane groups. Given that, in vivo, RGG motifs are often asymmetrically dimethylated by specific cellular methylases, our data add support to the idea that this type of methylation is a key mechanism for cells to regulate the interaction of the RGG proteins with their cellular partners.

Identification of agmatinase from Vibrio splendidus and its roles in modulating arginine metabolism of Apostichopus japonicus

Innate immunity is the first line of defense against invading pathogens. However, pathogenic bacteria have developed various mechanisms, such as direct competition for common substrates and transformation of metabolic regulations of the host, which allow them to escape from the immune surveillance system and enhance their survival. In this study, the Vibrio splendidus agmatinase (designated as Vsagmatinase) gene was cloned, and its biological activities in Apostichopus japonicus coelomocytes were analyzed. Vsagmatinase encoded an open reading frame of 930 bp, which translated into a predicted protein of 309 amino acid residues. SMART analysis and multiple sequence alignment indicated that Vsagmatinase displayed an arginase domain, and the conserved histidine (H151 and H163) and aspartic acid (D125, D149, D153, D231, and D233) residues for catalytic activity were all strictly conserved in this domain. Moreover, four conserved residues, namely, Asp153, His163, Thr245, and Glu275, that bonded with the guanidinium portion of agmatine were conserved in V. splendidus agmatinase. The recombinant protein was expressed in Escherichia coli (BL21), and the purified Vsagmatinase showed high agmatinase activity with agmatine substrate. By site-directed mutagenesis, the agmatinase activity of mutated Vsagmatinase was reduced to approximately 8.9%–9.4% of wild-type activity under different Vsagmatinase protein concentrations, indicating that the Glu275 residue was necessary for the guanidinium group of agmatine. Notably, injection of Vsagmatinase in coelomocytes could significantly increase both the mRNA expression levels and enzyme activities of Ajarginase and Ajagmatinase and obviously inhibited AjNOS transcript and NO content in A. japonicus. By contrast, mutated Vsagmatinase downregulated the activity of arginase and promoted NO production at 12 h after injection. Our findings suggested that Vsagmatinase served as the competitor that utilizes host agmatine and modulates arginine metabolism in A. japonicus.

Novel photoluminescence enzyme immunoassay based on supramolecular host-guest recognition using L-arginine/6-aza-2-thiothymine-stabilized gold nanocluster

A new photoluminescence (PL) enzyme immunoassay was designed for sensitive detection of aflatoxin B1 (AFB1) via an innovative enzyme substrate, 6-aza-2-thiothymine-stabilized gold nanocluster (AAT-AuNC) with L-arginine. The enzyme substrate with strong PL intensity was formed through supramolecular host-guest assembly between guanidine group of L-arginine and AAT capped on the surface of AuNC. Upon arginase introduction, the captured L-arginine was hydrolyzed into ornithine and urea, thus resulting in the decreasing PL intensity. Based on this principle, a novel competitive-type immunoreaction was first carried out on AFB1-bovine serum albumin (AFB1-BSA) conjugate-coated microplate, using arginase-labeled anti-AFB1 antibody as the competitor. Under the optimum conditions, the PL intensity increased with the increment of target AFB1, and allowed the detection of the analyte at concentrations as low as 3.2 pg mL−1 (ppt). Moreover, L-arginine-AAT-AuNC-based PL enzyme immunoassay afforded good reproducibility and acceptable specificity. In addition, the accuracy of this methodology, referring to commercial AFB1 ELISA kit, was evaluated to analyze naturally contaminated or spiked peanut samples, giving well-matched results between two methods, thus representing a useful scheme for practical application in quantitative monitoring of mycotoxins in foodstuff.

ВЛИЯНИЕ ПРИРОДЫ И ПОЛОЖЕНИЯ КАРБОФУНКЦИОНАЛЬНОГО ЗАМЕСТИТЕЛЯ НА СОРБЦИОННУЮ АКТИВНОСТЬ ПОЛИАЛКИЛСИЛСЕСКВИОКСАНОВ

An extensive number of organic sorbents can be used for extraction of precious metals from solutions, among which organosilicon sorbents deserve a particular attention. The sorption activity of organosilicon sorbents is determined by the nature of the functional group and its position in the polymer chain. In this study, the effect of the nature and position of the functional substituent on the sorption activity of polyalkylsilsesquioxanes with respect to Ag (I) and Au (III) ions is analyzed for polymer homologues and polymer analogs with sulfhydril, sulphonic, thioalkylamine, guanidine, biguanidine, malonodiamide and phthalamide groups. It is shown that the sorption activity of the com-pounds under study increases during a transition from polyalkylsilsesquioxanes, containing chemically active groups in the a-position, to their polymer homologues, containing these groups in the b- и g-position. The sorption activity of complexing polymers is determined by the stability of the chelate compounds formed, the number of donor-active atoms in the functional groups and their spatial position facilitating the formation of complexes.

New Metal Complexes Derived from Guanidine-Containing Dialdehyde Cellulose

New metal-polymer complexes of iron-containing composites of dialdehyde cellulose with guanidine acrylate or methacrylate have been developed. The structure and properties of these materials have been established by physicochemical testing. The polymeric iron-containing complexes obtained by radical polymerization (in situ) are formed due to intra- and intermolecular coordination of the metal ions with carboxylate oxygen atoms, and amino group nitrogen atoms of the guanidine fragment as well as hydroxyl groups of dialdehyde cellulose. The complexes obtained by mixing the metal salt with polymers in aqueous solution are formed due to replacement of water molecules in the coordination sphere of the solvated metal ions by hydroxyl groups of dialdehyde cellulose and the reaction of metals with carboxylate ions and guanidine groups of the polymer located on the composite surface. Guanidine-containing cellulose composites were found to be effective matrices for stabilizing the size of the growing particles containing a new metallic phase and to form polymer complexes with a narrow size distribution of both micro- and nanoparticles. These results suggest that the synthesized compounds hold promise for reagent transport when using composites as catalysts for various chemical reactions or for targeted delivery of drugs.

Design and synthesis of constrained bicyclic molecules as candidate inhibitors of influenza A neuraminidase

The rise of drug-resistant influenza A virus strains motivates the development of new antiviral drugs, with different structural motifs and substitution. Recently, we explored the use of a bicyclic (bicyclo[3.1.0]hexane) analogue of sialic acid that was designed to mimic the conformation adopted during enzymatic cleavage within the neuraminidase (NA; sialidase) active site. Given that our first series of compounds were at least four orders of magnitude less active than available drugs, we hypothesized that the new carbon skeleton did not elicit the same interactions as the cyclohexene frameworks used previously. Herein, we tried to address this critical point with the aid of molecular modeling and we proposed new structures with different functionalization, such as the introduction of free ammonium and guanidinium groups and ether side chains other than the 3-pentyl side chain, the characteristic side chain in Oseltamivir. A highly simplified synthetic route was developed, starting from the cyclopropanation of cyclopentenone and followed by an aziridination and further functionalization of the five-member ring. This allowed the efficient preparation of a small library of new bicyclic ligands that were characterized by enzyme inhibition assays against influenza A neuraminidases N1, its H274Y mutant, and N2. The results show that none of the new structural variants synthesized, including those containing guanidinium groups rather than free ammonium ions, displayed activity against influenza A neuraminidases at concentrations less than 2 mM. We conclude that the choice and positioning of functional groups on the bicyclo[3.1.0]hexyl system still need to be properly tuned for producing complementary interactions within the catalytic site.

Postelongation Strategy for the Introduction of Guanidinium Units in the Main Chain of Helical Oligourea Foldamers.

The synthesis of hybrid urea-based foldamers containing isosteric guanidinium linkages at selected positions in the sequence is described. We used a postelongation approach whereby the guanidinium moiety is introduced by direct transformation of a parent oligo(urea/thiourea) foldamer precursor. The method involves activation of the thiourea by treatment with methyl iodide and subsequent reaction with amines. To avoid undesired cyclization with the preceding urea moiety, resulting in heterocyclic guanidinium formation in the main chain, the urea unit preceding the thiourea unit in the sequence was replaced by an isoatomic and isostructural γ-amino acid. The approach was extended to solid-phase techniques to accelerate the synthesis of longer and more functionalized sequences. Under optimized conditions, an octamer hybrid oligomer incorporating a central guanidinium linkage was obtained in good overall yield and purity. This work also reports data related to the structural consequences of urea by guanidinium replacements in solution and reveals that helical folding is substantially reduced in oligomers containing a guanidinium group.

Cybastacines A and B: Antibiotic Sesterterpenes from a Nostoc sp. Cyanobacterium.

Cybastacines A (1) and B (2) were discovered as a novel pentacyclic sesterterpenoid-alkaloid skeleton structure, with a guanidinium group. These molecules were isolated from a Nostoc sp. cyanobacterium collected in the Canary Islands. Their structures were elucidated primarily by a combination of spectroscopic analyses and X-ray diffraction. These compounds showed antibiotic activities against several clinically relevant bacterial strains.

Weighted Averaging Scheme and Local Atomic Descriptor for pKa Prediction Based on Density Functional Theory.

As a continuation of our work on developing a density functional theory-based pKa predictor, we present conceptual improvements to our previously published shell model, which is a hierarchical organization of pKa training sets and which, in principle, covers all chemical space. The improvements concern the way the studied chemical compound is associated with the data points from the training sets. By introducing a new descriptor of the local atomic environment which foregoes dependence on chemical bonding and connectivity, we are able to automatically locate molecules from the training set that are most relevant to the proton dissociation equilibrium under study. This new scheme leads to the prediction of a single pKa value weighted across multiple training sets and thus patches a defect disclosed in the formulation of our previous model. Using the new parametrization approach, the pKa prediction gets rid of outliers reported in previous applications of our approach, eliminates ambiguity in interpreting the results, and improves the overall accuracy. Our new treatment accounts for multiple conformations both on the level of energetics and parametrization. Illustrative results are shown for several types of chemical structures containing guanidine, amidine, amine, and phenol functional groups, and which are representative of practically important large and flexible drug-like molecules. Our method's performance is compared to the performance of other previously published pKa prediction methods. Further possible improvements to the organization of the training sets and the potential application of our new local atomic descriptor to other kinds of parametrizations are discussed.

Gold Nanoparticle-Based Photoluminescent Nanoswitch Controlled by Host-Guest Recognition and Enzymatic Hydrolysis for Arginase Activity Assay.

The development of simple yet powerful methods for monitoring enzyme activity is of great significance. Herein, a facile, convenient, cost-effective, and continuous fluorescent method for the detection of arginase and its inhibitor has been reported based on a host-guest interaction-controlled and enzymatic hydrolysis-controlled luminescent nanoswitch. The fluorescence intensity of 6-aza-2-thiothymine-stabilized gold nanoparticle (ATT-AuNP) is enhanced by l-arginine, owing to the formation of a supramolecular host-guest assembly between the guanidine group of l-arginine and ATT molecules capped on the AuNP surface. However, hydrolysis of l-arginine, catalyzed by arginase, leads to a decrease in the fluorescence intensity of l-arginine/ATT-AuNPs hybrids. Upon incorporation of the arginase inhibitor l-norvaline, the fluorescence of the ATT-AuNP-based detecting system is restored. The linear range of arginase activity determination is from 0.0625 to 1.15 U/mL and the limit of detection is 0.056 U/mL. The half-maximal inhibition value IC50 of l-norvaline is determined to be 5.6 mM. The practicability of this luminescent nanoswitch is validated by assaying the arginase activity in rat liver and monitoring the response of rat liver arginase to pharmacological agent. Compared to the existing fluorescent method of arginase activity assay, the approach demonstrated here does not involve any complicated technical manipulation, thereby greatly simplifying the detection steps. We propose that this AuNP-based luminescent nanoswitch would find wide applications in the field of life sciences and medicine.

Enhancement effect of p-iodophenol on gold nanoparticle-catalyzed chemiluminescence and its applications in detection of thiols and guanidine

In the present study, the effects of nine compounds on the luminol-O2 chemiluminescence (CL) reaction catalyzed by gold nanoparticles (Au NPs) were investigated. p-Iodophenol (PIP), known as a traditional enhancer in horseradish peroxidase (HRP)-catalyzed luminol-H2O2 CL reaction, exhibited the highest enhancement effect on the luminol-O2-Au NPs CL reaction. The addition of PIP at a final concentration of 1.25 mM to luminol-O2-Au NPs CL system enhanced the CL signal almost 30-fold. Interestingly, the enhanced CL reaction exhibited a slow and intense CL signal which is different from the CL profile of luminol-H2O2-Au NPs CL system reported in previously. The experimental conditions of the PIP enhanced luminol-O2-Au NPs CL system were investigated systematically in the present study. And the mechanism studies showed that superoxide anion (O2•-) and singlet oxygen (1O2) generated from dissolved oxygen played an important role during the CL reaction. Furthermore, the effects of some organic compounds on the enhanced CL system were investigated. The results showed that compounds containing -SH and guanidine group can inhibit the signal of the enhanced CL reaction indicating the applicability of the proposed CL reaction for the detection of such compounds.

Studies on neuraminidase inhibition

AbstractNeuraminidase (NA) inhibitors are a class of antiviral drugs developed to target the influenza virus— a highly contagious virus that can cause severe respiratory illness and death. Although several NA inhibitors have been developed in the last decade, it is still poorly understood how they interact in the active site of the enzyme and which chemical and structural features potentiate their inhibitory activity. Taking this into account, we analyze in this article the inhibitory activity of 236 known NA inhibitors using molecular docking simulations. The protocol performed in this work, based on AutoDock, demonstrated to be very efficient in differentiating NA inhibitors with ΔGbinding above −11.7 kcal·mol−1. The results have shown that the best inhibitors are those that closely resemble the structure of the natural substrate, but explore additional areas of the active site with which they interact strongly and, therefore, potentiate their inhibitory activity. The best NA inhibitors are characterized by a central saturated six‐member ring filling almost completely the space available in the active site pocket. In addition, they contain both a carboxylate and an acetamide group, bound to the central ring structure, which allow them to interact with five arginines, organized in a triad (Arg371, Arg118, Arg292) and a pair (Arg151, Arg152). These interactions are very strong and act as two anchors that fix the compounds in the active site. The inhibitory activity of the compounds is improved if they have hydrophobic groups pointing toward a hydrophobic region of the active site, where Ile222 is located, and when they have amine or guanidine groups pointing toward three glutamates (Glu277, Glu276, Glu227). The studies performed here lay the foundations for the rational design of new and more efficient drugs to fight the influenza virus.

Reversible Phase Transition of Robust Luminescent Hybrid Hydrogels

AbstractWe report herein on remote control over a reversible phase transition of robust luminescent hybrid hydrogels as enabled by the rational selection and incorporation of photoswitches. Azobenzene units functionalized with a guanidinium group were utilized as the photoswitches and incorporated through a host–guest inclusion method involving α‐cyclodextrins functionalized with 2,6‐pyridinedicarboxylic acid (PDA) groups. While the guanidinium functional groups bind to the negatively charged Laponite matrix surface to connect organic and inorganic components, the PDA groups enable simultaneous coordination with different lanthanide metal ions, thus rendering the hydrogel broadly luminescent. Owing to its conformation‐dependent binding behavior with α‐cyclodextrin, the isomerization of azobenzene induced association or dissociation of the inclusion complexes and thus lead to a reversible photocontrolled sol↔gel phase transition of the luminescent hybrid hydrogels.

Reversible Phase Transition of Robust Luminescent Hybrid Hydrogels.

We report herein on remote control over a reversible phase transition of robust luminescent hybrid hydrogels as enabled by the rational selection and incorporation of photoswitches. Azobenzene units functionalized with a guanidinium group were utilized as the photoswitches and incorporated through a host-guest inclusion method involving α-cyclodextrins functionalized with 2,6-pyridinedicarboxylic acid (PDA) groups. While the guanidinium functional groups bind to the negatively charged Laponite matrix surface to connect organic and inorganic components, the PDA groups enable simultaneous coordination with different lanthanide metal ions, thus rendering the hydrogel broadly luminescent. Owing to its conformation-dependent binding behavior with α-cyclodextrin, the isomerization of azobenzene induced association or dissociation of the inclusion complexes and thus lead to a reversible photocontrolled sol↔gel phase transition of the luminescent hybrid hydrogels.

Formaldehyde-aminoguanidine condensation and aminoguanidine self-condensation products: syntheses, crystal structures and characterization.

Guanidine is the functional group on the side chain of arginine, one of the fundamental building blocks of life. In recent years, a number of compounds based on the aminoguanidine (AG) moiety have been described as presenting high anticancer activities. The product of condensation between two molecules of AG and one molecule of formaldehyde was isolated in the protonated form as the dinitrate salt (systematic name: 2,8-diamino-1,3,4,6,7,9-hexaazanona-1,8-diene-1,9-diium dinitrate), C3H14N82+·2NO3-, (I). The cation lacks crystallographically imposed symmetry and comprises two terminal planar guanidinium groups, which share an N-C-N unit. Each cation in (I) builds 14 N-H...O hydrogen bonds and is separated from adjacent cations by seven nitrate anions. The AG self-condensation reaction in the presence of copper(II) chloride and chloride anions led to the formation of the organic-inorganic hybrid 1,2-bis(diaminomethylidene)hydrazine-1,2-diium tetrachloridocuprate(II), (C2H10N6)[CuCl4], (II). Its asymmetric unit is composed of half a diprotonated 1,2-bis(diaminomethylidene)hydrazine-1,2-diium dication and half a tetrachloridocuprate(II) dianion, with the CuII atom situated on a twofold rotation axis. The planar guanidinium fragments in (II) have their planes twisted by approximately 77.64 (5)° with respect to each other. The tetrahedral [CuCl4]2- anion is severely distorted and its pronounced `planarity' must originate from its involvement in multiple N-H...Cl hydrogen bonds. It was reported that [CuCl4]2- anions, with a trans-Cl-Cu-Cl angle (Θ) of ∼140°, are yellow-green at room temperature, with the colour shifting to a deeper green as Θ increases and toward orange as Θ decreases. Brown salt (II), with a Θ value of 142.059 (8)°, does not fit the trend, which emphasizes the need to take other structural factors into consideration. In the crystal of salt (II), layers of cations and anions alternate along the b axis, with the minimum Cu...Cu distance being 7.5408 (3) Å inside a layer. The structures of salts (I) and (II) were substantiated via spectroscopic data. The endothermic reaction involved in the thermal decomposition of (I) requires additional oxygen. The title salts may be useful for the screening of new substances with biological activity.