Basic Nitrogen Atom Research Articles

Measurement of the Proton Affinities of a Series of Mono- and Biradicals of Pyridine.

The proton affinity (PA) of a neutral molecule is defined as the negative of the enthalpy change for the gas-phase reaction between a proton and the neutral molecule to produce the (charged) conjugate acid of the molecule. PA is a fundamental property that is related to the structure of a molecule and affects its reactivity. Very few PA values are available for basic organic monoradicals and none for biradicals. Here, the PA values for several σ-type carbon-centered pyridine-based monoradicals and biradicals have been experimentally determined by monitoring proton transfer from the protonated mono- and biradicals to reference bases with known proton affinities as a function of time in Fourier-transform ion cyclotron resonance (FT-ICR) and linear quadrupole ion trap (LQIT) mass spectrometers. A procedure was developed for both instruments that permits differentiation between exo- and endothermic proton transfer reactions. The PA values of all the (bi)radicals studied were found to be lower than that of pyridine. This is rationalized based on the electron-withdrawing nature of the radical site(s). Thus, the PA values decrease in the order: pyridine > monoradicals > biradicals. The PA values of the monoradicals were also found to increase (making the protonated radicals less acidic) as the distance between the basic nitrogen atom and the radical site increases. Similar behavior was found for the biradicals, with one exception: 3,5-didehydropyridine has a larger PA (215.3 ± 3.3 kcal mol-1) than 3,4-didehydropyridine (PA = 213.4 ± 3.3 kcal mol-1) even though the latter biradical has one radical site farther away from the basic nitrogen atom. Quantum chemical calculations of the PAs of the (bi)radicals are in reasonably good agreement with the experimentally determined values. At the DFT (B3LYP), CCSD(T), and CASPT2 levels of theory, the mean unsigned errors are 2.3, 1.7, and 2.1 kcal mol-1.

Discovery of δ opioid receptor full agonists lacking a basic nitrogen atom and their antidepressant-like effects

We have recently reported that the elaboration of the N-substituent in the δ opioid receptor (DOR) antagonist naltrindole (NTI) enabled the regulation of the DOR activities from full inverse agonists to weak partial agonists. The investigations of amide-type NTI derivatives revealed that N-phenylacetyl and N-dihydrocinnamoyl derivatives 3a and 3b were DOR full agonists. The same transformations were applied to a DOR agonist KNT-127 to provide the more potent DOR agonists 6a and 6b. Among the tested compounds, the most efficacious compound 6a showed dose-dependent antidepressant-like effects in the mouse forced swim test. The antidepressant-like effects by 6a seemed to be more potent than those of KNT-127, which is a more potent DOR agonist in in vitro assays. The amide-type compound like 6a may more fully penetrate into the central nervous system.

Lipid-Modified Aminoglycosides for mRNA Delivery to the Liver.

Cationic lipid nanoparticles (LNPs) are widely used as carriers for delivery of nucleic acids. Most synthetic routes toward cationic lipids have derived from simple amine cores. Greater chemical diversity can be obtained through starting with natural products containing basic nitrogen atoms, which offers routes to more complex molecules. Natural building blocks are not extensively explored, such as aminoglycosides, which are both structurally and functionally interesting for developing new carriers for nucleic acid delivery. Herein, cationic lipid-modified aminoglycosides (CLAs) are explored as a family of vehicles for messenger RNA (mRNA) delivery. CLAs are synthesized from natural existing aminoglycosides coupling with alkyl epoxides and acrylates. The top hit (GT-EP10) is able to deliver Luc mRNA to C57BL/6 mice at a dose of 0.05 mg kg-1 to achieve a 107 average luminescence intensity in the liver. The Lox-Stop-Lox tdTomato mouse model is used to further demonstrate that this efficient mRNA delivery system can be potentially used for gene editing. Successful delivery of human erythropoietin mRNA shows that CLA-based LNPs have promising opportunities for delivery of therapeutic nucleic acids in the future.

Preparation of nitrogen-doped hierarchical porous carbon materials by a template-free method and application to CO2 capture

The excessive emission of greenhouse gases such as carbon dioxide (CO2) increases the average surface temperature of the earth through the greenhouse effect. Nitrogen-doped porous carbon materials are considered to be promising solid adsorbents for CO2 capture. Herein we report a synthesis of nitrogen-doped porous carbon materials using a template-free method. The effects of different nitrogen sources and different carbon sources on the CO2 adsorption performance of porous carbon materials were studied.The result indicated the ethylenediamine based porous carbon material showed the highest micropore volume and the most surface basic nitrogen atoms, and both lead to good CO2 adsorption performance. Moreover, it was found that the sample maintained thermal and chemical stability in a long-term (ten cycles) CO2 adsorption/desorption experiment.

Advanced Strategies for Production of Natural Products in Yeast.

Natural products account for more than 50% of all small-molecule pharmaceutical agents currently in clinical use. However, low availability often becomes problematic when a bioactive natural product is promising to become a pharmaceutical or leading compound. Advances in synthetic biology and metabolic engineering provide a feasible solution for sustainable supply of these compounds. In this review, we have summarized current progress in engineering yeast cell factories for production of natural products, including terpenoids, alkaloids, and phenylpropanoids. We then discuss advanced strategies in metabolic engineering at three different dimensions, including point, line, and plane (corresponding to the individual enzymes and cofactors, metabolic pathways, and the global cellular network). In particular, we comprehensively discuss how to engineer cofactor biosynthesis for enhancing the biosynthesis efficiency, other than the enzyme activity. Finally, current challenges and perspective are also discussed for future engineering direction.

(Het)aryl Difluoromethyl‐Substituted β‐Alkoxyenones: Synthesis and Heterocyclizations

An efficient approach to the preparation of β‐alkoxyenones bearing (het)aryl difluoromethyl substituents is described. The method included acylation of acyclic or cyclic vinyl ethers with (het)aryl difluoroacetyl chlorides. The method worked well for most substrates, except aryl‐substituted derivatives bearing electron‐donating groups in o‐ or p‐positions, and heteroaromatic compounds bearing sufficiently basic nitrogen atom. Synthetic utility of (het)aryl difluoromethyl‐substituted β‐alkoxyenones as CCC bis‐electrophiles was demonstrated by heterocyclizations with common 1,2‐ and 1,3‐bis‐nucleophiles leading to compounds with (het)aryl–CF2–(het)aryl motif, in particular (het)aryl difluoromethyl‐substituted pyrazoles, isoxazoles, and pyrimidines – promising chemotypes for drug discovery.

Synthesis and HSA-interaction of a new mixed ligand Cu-isothiosemicarbazonato complex with adenine nucleobase

The synthesis, characterization, crystal structure and HSA-binding of a mixed ligand Cu-isothiosemicarbazonato complex with adenine nucleobase as an auxiliary ligand are reported. X-ray crystallography indicates that the cationic complex has a binuclear centrosymmetric structure in which the isothiosemicarbazone molecule coordinates to copper as a tridentate NNO ligand. Adenine participates in the structure of complex in neutral 7-H tautomer form in which N9 as its most basic nitrogen atom completes the square planar geometry. The planar complex entities are anti-parallel stacked and joined by means of long Cu–O bonds involving oxygen atoms from the other isothiosemicarbazone molecule, giving a [4 + 1] square pyramidal coordination around the copper ion. Adenine molecule plays a pivotal role in establishing intermolecular hydrogen bonding in the supramolecular structure. HSA interactions of the complex are investigated thorough spectroscopic and theoretical methods. Emission studies indicate that the complex quenches fluorescence emission of HSA by a static mechanism. They also show that hydrophobic forces are primary interactions between complex and protein. Circular dichroism studies illustrate that the complex induces unfolding of HSA through converting part of the α-helical content to β-structures and random coils. Finally, docking studies indicate that the complex places in the upper part of interdomain region of HSA.

CHARACTERISTIC OF COMPLEX COMPOUNDS OF CUPRUM (II) NITRATE WITH ALIPHATIC AMINES PYRIDINE AND ITS DERIVATIVES IN CRYSTAL STATE

Complex compounds of CuCl 2 і Cu(NO 3 ) 2 with aliphatic amines in a crystalline state from alcohol solutions were obtained. The composition of the obtained compounds was determined by the method of equilibrium shift, molar ratios and intersection of the curves. Their electronic and IR spectra were studied, and a wide asymmetric absorption band was detected in the near region with a maximum of 870 - 900 nm. This band is characteristic of compounds of a tetrigonally curved octahedral configuration. The formation of complex compounds Cuprum (II) with amines of 1:1, 1:2 composition was established. Measured vibrational spectra in the region of 500 to 200 см -1 . IR-spectra of samples of complex compounds Cuprum (II) with the aliphatic amines, pyridine and its derivatives was measured as a suspension in vaseline oil. The measurements were carried out on an IKS-228 spectrophotometer. The frequency of stretching vibrations Me-N characterizes the coordination bond. The stretching vibrations of Me-N should manifest themselves in the low-frequency region as a result of a significant mass of the metal atom and the relatively low strength of the coordination bond. The IR spectra indicate Me-N stretching vibrations, which characterize the coordination bond. For aliphatic amines, absorption bands were identified in the region of 440–420 см -1 , which are assigned to V(Cu–N) vibrations. The bands in this region indicate coordination through the base nitrogen atom. The absorption bands of the ligands in the region of 210-220 см -1 disappear in the complex compounds. Most of the frequencies in complex compounds are explained by the dual nature of the σ- and π- dative interactions. In coordination compounds of Cu(NO 3 ) 2 with pyridine and its derivatives, an increase in vibration frequencies is observed with an increase in the stability of complex compounds, which is explained by the double nature of the bond (σ,-and π-dative interaction). Complex compounds were studied by differential thermal analysis. As a result, it was concluded that the nature of the decay of the complexes is affected by the nature of the ligand, complexing agent, electronegativity and polarizing properties of the ligand, steric effects and the nature of cations. The process of breaking the coordination bond for primary and secondary aliphatic amines occurs stepwise, and for tertiary amines in one step. At the first stage, one ligand molecule is cleaved, and at the second, the second molecule. Secondary amines have small cleavage. With an increase in the spatial factors of amines, the thermal stability of the complexes decreases.

An electrophysiological characterization of naturally occurring tobacco alkaloids and their action on human α4β2 and α7 nicotinic acetylcholine receptors

Nicotinic acetylcholine receptor (nAChR) subtype-selective pharmacological profiles of tobacco alkaloids are essential for understanding the physiological effects of tobacco products. In this study, automated electrophysiology was used to functionally characterize the effects of distinct groups of tobacco alkaloids on human α4β2 and α7 nAChRs. We found that, in tobacco alkaloids, pyridine as a hydrogen bond acceptor and a basic nitrogen atom at a distance of 4–7 Å are pharmacophoric elements necessary for molecular recognition by α4β2 and α7 nAChRs with various degrees of selectivity, potency, and efficacy. While four alkaloids—nicotine, nornicotine, anabasine and R-anatabine—potently activated α4β2, they were also weak agonists of α7 nAChRs. Nicotine was the most potent agonist of α4β2, while anabasine elicited the highest activation of α7. None of the tobacco alkaloids enhanced nAChR activity elicited by the endogenous ligand acetylcholine; therefore, none was considered to be a positive allosteric modulator (PAM) of either α4β2 or α7 nAChRs. In contrast, we identified tobacco alkaloids, such as the tryptophan metabolite 6-hydroxykynurenic acid, that decreased the activity of both α4β2 and α7 nAChRs. Our study identified a class of alkaloids with positive and negative effects against human α4β2 and α7 nAChRs. It also revealed human α4β2 to be the principal receptor for sensing the most abundant alkaloids in tobacco leaves.

Crystal Structure of Bacterial Cystathionine Γ-Lyase in The Cysteine Biosynthesis Pathway of Staphylococcus aureus

Many enzymes require pyridoxal 5’-phosphate (PLP) as an essential cofactor and share active site residues in mediating diverse enzymatic reactions. Methionine can be converted into cysteine by cystathionine γ-lyases (CGLs) through a transsulfuration reaction dependent on PLP. In bacteria, MccB, also known as YhrB, exhibits CGL activity that cleaves the C–S bond of cystathionine at the γ position. In this study, we determined the crystal structure of MccB from Staphylococcus aureus in its apo- and PLP-bound forms. The structures of MccB exhibited similar molecular arrangements to those of MetC-mediating β-elimination with the same substrate and further illustrated PLP-induced structural changes in MccB. A structural comparison to MetC revealed a longer distance between the N-1 atom of the pyridine ring of PLP and the Oδ atom of the Asp residue, as well as a wider and more flexible active site environment in MccB. We also found a hydrogen bond network in Ser-water-Ser-Glu near the Schiff base nitrogen atom of the PLP molecule and propose the Ser-water-Ser-Glu motif as a general base for the γ-elimination process. Our study suggests the molecular mechanism for how homologous enzymes that use PLP as a cofactor catalyze different reactions with the same active site residues.

Effects of primary amine-based coatings on microglia internalization of nanogels

Nanogels represent a pivotal class of biomaterials in the therapeutic intracellular treatment of many diseases, especially those involving the central nervous system (CNS). Their biocompatibility and synergy with the biological environment encourage their cellular uptake, releasing the curative cargo in the desired area. As a main drawback, microglia are generally able to phagocytize any foreign element overcoming the blood brain barrier (BBB), including these materials, drastically limiting their bioavailability for the target cells. In this work, we investigated the opportunity to tune and therefore reduce nanogel internalization in microglia cultures, exploiting the orthogonal chemical functionalization with primary amine groups, as a surface coating strategy. Nanogels are designed by following two methods: the direct grafting of aliphatic primary amines and the linkage of -NH2 modified PEG on the nanogel surface. The latter synthesis was proposed to evaluate the combination of PEGylation with the basic nitrogen atom. The achieved results indicate the possibility of effectively modulating the uptake of nanogels, in particular limiting their internalization using the PEG-NH2 coating. This outcome could be considered a promising strategy for the development of carriers for drugs or gene delivery that could overcome microglia scavenging.

Use of 155Gd, 151Eu, 166Er Mössbauer spectroscopy to characterize heterodinuclear Ln–Ln′ complexes

Use of 155Gd Mössbauer spectroscopy allows a straightforward characterization of heterodinuclear Ln-Ln′ complexes (LLnLn′ (NO3)3·(H2O)2) with a tripodal ligand L, possessing two different N4O3 and O3O3 coordination sites. Thanks to the isomer shift value, the location of the GdIII ion is confirmed; the Gd atom in the Gd–Ln′ series (Ln′ = Ce, Nd, Eu) occupies the inner N4O3 site with a eight-coordination (N4O3 + O), but on the other hand the Gd atom in the Ln–Gd series (Ln = Dy, Er, Yb) resides in the outer O3O3 site with a ten-coordination (O3O3 + O2 + O2). The smaller isomer shift values for the former indicate that coordination of the basic nitrogen atoms enhances the 6s orbital population. With the help of 151Eu Mössbauer spectroscopy, we demonstrate that the Gd–Eu entity is a genuine heterodinuclear complex, in which the GdIII ion is located in the inner site and the EuIII ion in the outer oxygenated site. This result highlights the feasibility of our synthetic process described earlier to introduce in a heterodinuclear complex two consecutive ions of the periodic table. And the slow paramagnetic relaxation observed in the 166Er Mössbauer spectrum of the Er–Gd complex confirms presence of a magnetic interaction in the genuine Er–Gd complex.

DFT and single crystal analysis of the pyrimethamine-based novel co-crystal salt: 2,4-diamino-5-(4-chloro-phenyl)-6-ethylpyrimidin-1-ium:4-hydroxybenzoate:methanol:hydrate (1:1:1:1) (DEHMH)

The present work is related to the synthesis, single crystal analysis, and computational investigation of pyrimethamine co-crystal salt with 4-hydroxybenzoic acid in methanol. The study shows that hydrogen bonding interactions are responsible for the stabilized 3-dimensional network. In the title compound, protonation of the pyrimethamine molecule results in the more basic nitrogen atom present in the 1,3-diazine ring to form a cation which interacts with the carboxylate (the conjugate base) of 4-hydroxybenzoic acid. Moreover, the computational study including analyses of charge distribution, frontier molecular orbitals, reactivity parameters, and molecular electrostatic potential has been also performed for this compound. Both the experimental and computational results showed the formation of intermolecular hydrogen bonding and electrostatic interactions that suggest the increased reactivity and potential biological activity of the compound. The current compound can have potential future applications in pharmacology for the production of new antimalarial drugs.

Development of Novel δ Opioid Receptor Inverse Agonists without a Basic Nitrogen Atom and Their Antitussive Effects in Mice.

Our previous results showed that naltrindole (NTI) derivatives with certain types of electron-withdrawing groups as an N-substituent showed δ opioid receptor (DOR) inverse agonistic activities. We therefore synthesized N-acylated NTI derivatives 3a-e and observed that N-benzoyl and N-cyclopropanecarbonyl derivatives SYK-736 (3b) and SYK-623 (3c) were DOR full inverse agonists and the N-acryloyl derivative 3d was a DOR partial inverse agonist. SKY-623 was over 110-fold more potent than the reference compound ICI-174,864. Both naltriben (NTB) and 7-benzylidenenaltrexone (BNTX) derivatives with N-benzoyl and N-cyclopropanecarbonyl groups were also DOR full inverse agonists. These N-acylated inverse agonists are interesting compounds because they have no basic nitrogen atom, which has been demonstrated to be an important pharmacophore. NTI and BNTX-type DOR inverse agonists SYK-623 and SYK-723 (12c) showed dose-dependent antitussive effects in a mouse cough model induced by citric acid exposure. The antitussive effects by SYK-623 and SYK-723 were significantly attenuated by pretreatment with DOR agonist SNC80.

The complexation of 2,4-dinitrophenol with basic drugs: Acid + base = salt

Different drugs containing a basic nitrogen atom were crystallised with 2,4-dinitrophenol to study the mode of complexation in search of an antidote to 2,4-dinitrophenol poisoning. The protonated forms of quininium, quinidinium and trazodonium form N–H···O hydrogen bonds to the deprotonated O atom of the 2,4-dinitrophenolate anion, whereas haloperidolium forms a bifurcated N–H···(O,O) hydrogen bond to the deprotonated O atom of 2,4-dinitrophenol and an O atom of the adjacent nitro group. Hydrogen-bonded chains occur in the quininium, quinidinium and haloperidolium crystal structures, whereas the trazodonium structure consists of ion pairs. These results are discussed with a view to lowering the toxicity of 2,4-dinitrophenol in the body in the case of an overdose.

Aluminum complexes with Schiff base bridged bis(indolyl) ligands: synthesis, structure, and catalytic activity for polymerization of rac-lactide.

A series of Schiff base bridged bis(indolyl) ligands were developed for aluminum chemistry. The reactions of AlEt3 or AlMe3 with the Schiff base bridged bis(indolyl) proligands R1(-N[double bond, length as m-dash]CHC8H5NH)2 (R1 = -CH2CH2- (H2L1); -CH2CH2CH2- (H2L2); -CH2CMe2CH2- (H2L3); rac-Cy (H2L4); and R,R-Cy (H2L5)) were studied leading to the synthesis of a series of aluminum alkyl complexes L1AlEt (1)-L5AlEt (5) and L3AlMe (3b) in good yields, while the reaction of H2L3 with Al(OiPr)3 gave the aluminum alkoxide complex L3AlOiPr (3a). These aluminum complexes were characterized by spectroscopic methods and elemental analyses. The solid state structures of the aluminum complexes 1-5 and 3a were confirmed by the X-ray diffraction study. X-ray analyses revealed that the aluminum centre in these complexes is five-coordinated. The coordination geometry is between square pyramidal and trigonal bipyramidal. In the presence of 1 equiv. of isopropanol, the aluminum alkyl complexes exhibited notable activity towards the ring-opening polymerization of rac-lactide at 70 °C in toluene, with good control over molecular weights and dispersities. The substituents and the length of the bridging part between the two Schiff base nitrogen atoms have an influence on either the tacticity of isolated polymers or the rate of polymerization. The kinetics of complex L3AlOiPr (3a) in C6D6 was also investigated, and the experimental results revealed that the rate of polymerization was first-order with respect to rac-lactide.

Interconnection of sulfides and sulfoxides in medicinal chemistry.

Aromatic heterocycles with basic nitrogen atoms as well as carboxylic acid derivatives are the dominating chemical space in the universe of drug-like molecules. These established and exceedingly evaluated structural motifs have to be combined with elements of diversity in order to chart less well-explored galaxies of chemical space and to be able to tackle seemingly undruggable targets. Flat scaffolds should be replaced by shapely molecular cores. In this context, it has been unheeded that phenyl rings in diaryl sulfides are less co-planar than in ethers and that the metabolic interconnection of sulfides and sulfoxides offers advantages that are unalike from the chemistry of amines and N-oxides in the CHN-O world. Moreover, σ-hole potentials increase with the polarizability of the atom N < P < O < S and do not only play a role in long-time overlooked halogen bonds. Examples for λ2 , λ4 , and λ6 S-based functionalities related to improved solubility, reduced drug resistance, linkers in drug conjugates, drug-targeting to parasites, and as basis for drug monitoring in sports are given and discussed.

Toxicological Effects of Berberine and Sanguinarine.

Berberine and Sanguinarine alkaloids belong to a group of naturally occurring chemical compounds that mostly contain basic nitrogen atoms. This group also includes some related compounds with neutral or weakly acidic properties. Alkaloids are produced by a large number of organisms including bacteria, fungi, plants, and animals. Berberine and Sanguinarine both are isoquinoline derivatives and belong to protoberberine and benzophenanthridines, respectively. Tyrosine or phenylalanine is common precursor for the biosynthesis of both. Sanguinarine [13-methyl (1,3) benzodioxolo(5,6-c)-1,3-dioxolo (4,5) phenanthridinium] is a toxin that kills animal cells through its action on the Na+-K+-ATPase transmembrane protein. Berberine, on the other hand, has been reported to cause cytotoxicity and adversely influence the synthesis of DNA. Several workers have reported varied pharmacological properties of these alkaloids as they exhibit antibacterial, antiasthma, anticancer, anti-inflammatory, and antidiabetic activities. This review article illustrates the toxicological effects of berberine and sanguinarine as well as mechanistic part of berberine and sanguinarine mediated toxicity in different living systems. This manuscript has included the lethal doses (LD50) of berberine and sanguinarine in different animals via different routs of exposure. Also, the effects of these alkaloids on the activities of some key enzymes, cell lines and organ development etc. have been summarized.

Theoretical Investigation of the Reaction Mechanism of Photodeamination Induced by Excited-State Intramolecular Proton Transfer of Cresol Derivatives.

The novel photodeamination process of cresol derivatives 1 and 3 has been reported experimentally ( J. Org. Chem . 2015 , 80 , 10817 ). However, a full theoretical interpretation of the mechanism is still lacking. In the present study, we aim to provide insight into the factors that promote the deamination reaction through density functional theory (DFT) and time-dependent DFT methods. Calculated absorption and emission spectra are in good agreement with the experimental results. Hydrogen-bond strengthening in the excited state has been verified by analyzing relevant bond parameters and vibrational frequencies as well as frontier molecular orbitals (FMOs), implying that hydrogen-bond interaction acts as the important parameter for the excited-state intramolecular proton-transfer (ESIPT) reaction. The proton-transfer and deamination reactions have been qualitatively analyzed through Gibbs free-energy reaction profiles in different electronic states. It can be concluded that the ESIPT and photodeamination reactions occur in the excited state. To further illustrate the photodeamination mechanism, the constructed 2D potential-energy surface indicates that the photodeamination reaction is infeasible without the ESIPT reaction. This work provides the first theoretical rationale for ESIPT-induced photodeamination occurring spontaneously because of protonation of a basic nitrogen atom.

N,N,N-Tris(tert-butoxycarbonyl)-l-arginine: five isoforms whose obtainment depends on procedure and scrupulous NMR confirmation of their structures

l-arginine is often covalently linked to vectors for gene or drug delivery as a means of increasing their transfection activity and reducing toxicity. This strategy relies on the protection of basic nitrogen atoms, for example, by employing the tert-butoxycarbonyl group. Our aim in the present work was to prepare the widely described α N, ω N, ω′ N-tris(tert-butyloxycarbonyl)-l-arginine as a single isomer in high yield and with high levels of purity for use in the esterification of dendrimers with several peripheral hydroxyl groups. Following three reported protocols which assured this goal, we observed the unexpected formation of four additional isomers. Using the first procedure, α N, ω N, ω′ N-tris(tert-butyloxycarbonyl)-l-arginine was never obtained. The second procedure delivered the desired compound as a mixture of geometric isomers (E/Z), while the third protocol led to a single isomer in high yield and purity, but with an unreported symmetrical structure. Since Boc protection is transient, this discovery would seem to be of little interest, but preliminary results from an ongoing investigation of the behavior of each of the isomers obtained in the esterification reactions of interest has shown that their reactivity depends on their structure. Although this research is ongoing, here we report a detailed description of these unexpected results, along with an NMR investigation focusing on the double-bond geometry and position which enabled confirmation of the structures.