Studies on the Imide-Amide Rearrangement of Cyclic Phosphorimidates

Abstract

The imide-amide rearrangement of cyclic phosphorirnidates 1 leads to the formation of phosphoramidates 3, either thermally (> 180°C) or by the action of a Lewis acid (BF₃ OEt₂, 60°C)¹. In an attempt to develop a synthetic pathway to β aminoalcohols based on this rearrangement, we have thoroughly studied the influence of the structure of the reactants on the Lewis acid catalysed rearrangement. This study brought some insight into the mechanism of this particular reaction, namely the identification of a new polymeric structure 2. not yet described, which is converted into 3 by thermolysis². The formation of 2 at rt was followed by ³ P NMR. In the case of R′? Ph, the reactivity observed for R₂N was: i-Pr₂N > Pyrrolidine > n-Bu²N For R²=i-Pr₂, the observed R′ group effect was: Bn > 4-NO₂Bn > Ph. No reaction was observed for R′ ? Ts, n-Oct. In the case of the groups R′ ? Bn and R₂=i Pr₂ the Lewis acid effect was also studied: BF₃OEt₂, BF₃MeOr-Bu, Sc(OTf)₃ or CITi(Oi-Pr)₃ or Me₂SnCl₂.     

Wireless Coupling of Conducting Polymer Actuators with Light Emission

Combining the actuation of conducting polymers with additional functionalities is an interesting fundamental scientific challenge and increases their application potential. Herein we demonstrate the possibility of direct integration of a miniaturized light emitting diode (LED) in a polypyrrole (PPy) matrix in order to achieve simultaneous wireless actuation and light emission. A light emitting diode is used as a part of an electroactive surface on which electrochemical polymerization allows direct incorporation of the electronic device into the polymer. The resulting free-standing polymer/LED hybrid can be addressed by bipolar electrochemistry to trigger simultaneously oxidation and reduction reactions at its opposite extremities, leading to a controlled deformation and an electron flow through the integrated LED. Such a dual response in the form of actuation and light emission opens up interesting perspectives in the field of microrobotics.     

Charge dependent behavior of PNA/DNA/PNA triplexes in the gas phase

Intact noncovalent complexes were studied in the gas phase using negative ion nano-ESI mass spectrometry. Among various noncovalent systems studied in the gas phase, the interaction of DNA strands with peptide nucleic acids (PNAs) presents a strong interest as biologically relevant systems. PNAs originally described by Nielsen are used as DNA mimics as possible medical agents by imprisoning DNA single strands into stable noncovalent complexes. Two types of PNAs were investigated in the PNA/DNA multiplex: the original Nielsen's PNA and a modified backbone PNA by the introduction of syn- and anti-(aminoethyl)thiazolidine rings. We first investigated the stoichiometry of PNA/DNA multiplexes formed in solution and observed them in the gas phase via qualitative kinetics of complementary strand associations. It resulted in observing PNA2/DNA triplexes (ts) as the multiply deprotonated species, most stable in both the solution and gas phase. Second, charge-dependant decompositions of these species were undertaken under low-energy collision conditions. It appears that covalent bond cleavages (base releasing or skeleton cleavage) occur from lower ts charge states rather than ts unzipping, which takes place from higher charge states. This behavior can be explained by considering the presence of zwitterions depending on the charge state. They result in strong salt-bridge interactions between the positively charged PNA side chain and the negatively charged DNA backbone. We propose a general model to clearly display the involved patterns in the noncovalent triplex decompositions. Third, the relative stability of three PNA2/DNA complexes was scrutinized in the gas phase by acquiring the breakdown curves of their ts(6-) form, corresponding to the ts unzipping. The chemical structures of the studied PNAs were chosen in order to evidence the possible influence of backbone stereochemistry on the rigidity of PNA2/DNA complexes. It provided significantly different stabilities via V(m) measurements. The relative gas-phase stability order obtained was compared to that found in solution by Chassaing et al., and shows qualitative agreement.     

Synthesis and Diels-Alder Reactions of a New Kind of Chiral Dienophiles: Cyclic Vinyl-p-tolylsulfilimines

A new kind of chiral dienophiles, cyclic vinyl-p-tolylsulfilimines (2a and 2b), were obtained from the corresponding (Z)-sulfinylacrylonitriles with HBF(4) and methanol. The asymmetric Diels-Alder reaction of optically pure 2a with cyclopentadiene under mild thermal or catalyzed conditions afforded only the endo-4a adduct with complete endo and pi-facial selectivities. The ability of the sulfilimine moiety to enhance the dienophilic reactivity of the double bond is similar to that of the sulfinyl group.     

In-situ ionic liquid-dispersive liquid-liquid microextraction method to determine endocrine disrupting phenols in seawaters and industrial effluents

We have evaluated an in-situ ionic liquid-dispersive liquid-liquid microextraction procedure for the determination of six endocrine disrupting phenols in seawaters and industrial effluents using HPLC. The optimized method requires 38???L of the water-soluble ionic liquid 1-butyl-3-methylimidazolium chloride, and 5?mL of seawater or industrial effluent. After appropriate work-up, a drop (~10???L) of an ionic liquid is formed that contains the analytes of interest. It is diluted with acetonitrile and injected into the HPLC system. This procedure is accomplished without heating or cooling the solutions. The method is characterized by (a) average relative recoveries of 90.2%, (b) enrichment factors ranging from 140 to 989, and (c) precisions (expressed as relative standard deviations) of less than 11% when using a spiking level of 10?ng?mL^?1. The limits of detection range from 0.8?ng?mL^?1 for 4-cumylphenol to 4.8?ng?mL^?1 for bisphenol-A.

Headspace-single drop microextraction (HS-SDME) in combination with high-performance liquid chromatography (HPLC) to evaluate the content of alkyl- and methoxy-phenolic compounds in biomass smoke

The content of ten phenolic compounds present in four different biomass smoke materials: rock rose (Cistus monpelienisis), prickly pear (Opuntia ficus indica), pine needles (Pinus canariensis), and almonds skin (Prunus dulcis), have been evaluated. The sampling method mainly consisted of a trap alkaline solution to solubilize the phenols, and was optimized by an experimental design. Average sampling efficiencies of 78.1% and an average precision value of 10.6% (as relative standard deviation, RSD), were obtained for the selected group of phenols. The trapped phenolates were further analyzed by a headspace-single drop microextraction (HS-SDME) procedure, in combination with high-performance liquid chromatography (HPLC) with UV detection. The optimum variables for the HS-SDME method were: 1-decanol as extractant solvent, 3.5 μL of microdrop volume, 2 mL of sample volume, a pH value of 2, saturation of NaCl, an extraction temperature of 60 °C, and an extraction time of 25 min. The optimized HS-SDME method presented detection limits ranging from 0.35 to 5.8 μg mL⁻¹, RSD values ranging from 0.7 to 7.4%, and an average relative recovery (RR) of 99.8% and an average standard deviation of 5.2. The average content of phenolic compounds in the biomass materials studied were 70, 161, 206 and 252 mg kg⁻¹ of biomass for prickly pear, almonds skin, rock rose, and pine needles, respectively. The main components of the smokes were vanillin, phenol and methoxyphenols, in all smoking materials studied.     

Separation of secondary alcohols via enzymatic kinetic resolution using fatty esters as reusable acylating agents

A two consecutive step procedure for the resolution-separation of secondary alcohols employing ethyl tetradecanoate in the presence of lipase allowed the enzymatic kinetic resolution of two target molecules, 1-phenylethanol and 6-methylhept-5-en-2-ol. (S)-1-Phenylethanol was isolated in a yield of 47% with an ee of 94% and (R)-1-phenylethanol in a yield of 51% with an ee of 95%. (S)-6-Methylhept-5-en-2-ol was isolated in a yield 47% and an ee of 87% and (R)-6-methylhept-5-en-2-ol in a yield 49% and an ee of 90%.     

Electronic Effects of 11β Substituted 17β-Estradiol Derivatives and Instrumental Effects on the Relative Gas Phase Acidity

Numerous studies have highlighted the role of the proton donor characteristics of the phenol group of 17??-estradiol (E₂) in its association with the estrogen receptor alpha (ER??). Since the substitutions at position C₍₁₁₎ have been reported to modulate this association, we hypothesized that such substitutions may modify the phenol acidity. Hence, phenol gas-phase acidity of nine C₍₁₁₎-substituted E₂-derivatives were evaluated using the extended Cooks?? kinetic method, which is a method widely used to determine thermochemical properties by mass spectrometry. To enhance accuracy in data collection we recorded data from several instruments, including quadrupole ion trap, triple quadrupole, and hybrid QqTOF. Indeed, we report for the first time the use of the QqTOF instrument to provide a novel means to improve data accuracy by giving access to an intermediate effective temperature range. All experimental gas-phase acidity values were supported by theoretical calculations. Our results confirmed the ability of distant substituents at C₍₁₁₎ to modulate the phenol acidity through electrostatic interactions, electron withdrawing inductive effects, and mesomeric effects. However, no relationship was found between the phenol gas-phase acidity of investigated steroids and their binding affinity for ER?? assessed in solution. Thus, our results highlight that the intrinsic properties of the hormone do not influence sufficiently the stabilization of the hormone/ER?? complex. It is more likely that such stabilization would be more related to factors depending on the environment within the binding pocket such as hydrophobic, steric as well as direct intermolecular electrostatic effects between ER?? residues and the substituted steroidal estrogens.     

Ionic liquids as desorption solvents and memory effect suppressors in heterocyclic aromatic amines determination by SPME–HPLC fluorescence

The beneficial effects of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF₄) ionic liquid (IL) as mobile phase additive, desorption solvent, and memory effect suppressor in solid-phase microextraction (SPME)–high-performance liquid chromatography with fluorescence detection for the determination of six heterocyclic aromatic amines have been evaluated for the first time. Several chromatographic parameters have been evaluated in the presence or absence of IL or using triethylamine as the most common mobile phase additive, with a Nova-Pak® C18 stationary phase. This IL was found to be clearly superior to triethylamine for efficiency as well as peak shape enhancement and sensitivity increase. SPME was chosen because it is faster than conventional extraction techniques and allowed us to minimize the use of organic solvents. However, memory effect may become a problem when a high-sensitivity detector is used. The appropriate conditions for the desorption step and to eliminate the memory effect involving BMIm-BF₄ were established and optimized. The method was applied for the determination of these compounds in commercial meat extracts.     

Traveling Wave Ion Mobility Mass Spectrometry and Ab Initio Calculations of Phosphoric Acid Clusters

Positive and negative ion electrospray mass spectra obtained from 50 mM phosphoric acid solutions presented a large number of phosphoric acid clusters: [(H₃PO₄)_n?+?zH] ^z+ or [(H₃PO₄)_n – zH] ^z– , with n up to 200 and z up to 4 for positively charged clusters, and n up to 270 and z up to 7 for negatively charged cluster ions. Ion mobility experiments allowed very explicit separation of the different charge states. Because of the increased pressures involved in ion mobility experiments, dissociation to smaller clusters was observed both in the trap and transfer areas. Voltages along the ion path could be optimized so as to minimize this effect, which can be directly associated with the cleavage of hydrogen bonds. Having excluded the ion mobility times that resulted from dissociated ions, each cluster ion appeared at a single drift time. These drift times showed a linear progression with the number of phosphoric atoms for cluster ions of the same charge state. Cross section calculations were carried out with MOBCAL on DFT optimized geometries with different hydrogen locations and with three types of atomic charges. DFT geometry optimizations yielded roughly spherical structures. Our results for nitrogen gas interaction cross sections showed that values were dependent on the atomic charges definition used in the MOBCAL calculation. This pinpointed the necessity to define a clear theoretical framework before any comparative interpretations can be attempted with uncharacterized compounds.