A novel second-order standard addition analytical method based on data processing with multidimensional partial least-squares and residual bilinearization

In the presence of analyte-background interactions and a significant background signal, both second-order multivariate calibration and standard addition are required for successful analyte quantitation achieving the second-order advantage. This report discusses a modified second-order standard addition method, in which the test data matrix is subtracted from the standard addition matrices, and quantitation proceeds via the classical external calibration procedure. It is shown that this novel data processing method allows one to apply not only parallel factor analysis (PARAFAC) and multivariate curve resolution-alternating least-squares (MCR-ALS), but also the recently introduced and more flexible partial least-squares (PLS) models coupled to residual bilinearization (RBL). In particular, the multidimensional variant N-PLS/RBL is shown to produce the best analytical results. The comparison is carried out with the aid of a set of simulated data, as well as two experimental data sets: one aimed at the determination of salicylate in human serum in the presence of naproxen as an additional interferent, and the second one devoted to the analysis of danofloxacin in human serum in the presence of salicylate.     

Nucleophilic difluoromethylenation of aldehydes and ketones using diethyl difluoro(trimethylsilyl)methylphosphonate

A new nucleophilic difluoromethylenation of aldehydes and ketones using diethyl difluoro(trimethylsilyl)methylphosphonate (1) has been achieved. The reactive carbanion species were generated under mild reaction conditions with a catalytic amount of initiator. This methodology was compatible with non-enolizable and in some cases with enolizable aldehydes and ketones and provided a straightforward access to phosphates of syn and anti 2,2-difluoro-1,3-diols.     

Cyclometallated platinum(II) compounds with imine ligands derived from amino acids: Synthesis and oxidative addition reactions

The reactions of [PtMe₂(μ-SMe₂)]₂ with imines 4-ClC₆H₄CHNCHRCO₂Me (R = H (1a), Me (1b), ⁱPr (1c), CH₂C₆H₄(4’-OH) (1d), C₆H₅ (1e), CH₂C₆H₅(1f)) derived from natural amino acids produced under mild conditions cyclometallated platinum(II) compounds [PtMe{κ²-(C,N)-4-ClC₆H₃CHNCHRCO₂Me}(SMe₂)] (2a-2f). These compounds gave the corresponding phosphine derivatives [PtMe{κ²-(C,N)-4-ClC₆H₃CHNCHRCO₂Me}(PPh₃)] (3a-3f). The corresponding cyclometallated platinum(IV) compounds [PtMe₂I{κ²-(C,N)-4-ClC₆H₃CHNCHRCO₂Me}(PPh₃)] (4) arising from intermolecular oxidative addition of methyl iodide were obtained with a high degree of stereo selectivity. Analogous results were obtained for imine 2,6-Cl₂C₆H₃CHNCH(CH₂C₆H₅)CO₂Me (1g) in a process involving intramolecular oxidative addition of a C-Cl bond. The obtained compounds were fully characterized including structure determinations for compounds 3f, 4d and 4f.     

Mechanistic pathways for oxidative addition of aryl iodides to the low-ligated diethanolamine palladium(0) complex in phosphine-free Heck reactions

A set of reactions of different activated olefins and aryl iodides with the trans-dichlorobis(diethanolamine-N)palladium(II) complex (trans-[PdCl₂(DEA)₂]) as a precatalyst was performed, in the presence of diethanolamine (DEA) as a weak base, and NaOEt as a strong base. It was established that the presence of NaOEt slightly lowered the yields, but significantly accelerated the reactions. This experimental finding is in agreement with our computational investigation that shows that significantly higher activation barrier is required for the preactivation reaction in the presence of a weak base than in the presence of a strong base. The reaction between the catalytically active DEA-Pd(0)-Cl complex, formed in the preactivation reaction, and iodobenzene was investigated using density functional theory. Two mechanisms for the oxidative addition of the activated complex were found. The first mechanism is based on a nucleophilic attack of Pd on I of iodobenzene, and yields an intermediate tetracoordinated Pd complex (aI2). The second mechanism begins with a nucleophilic attack of Pd on the benzene ring, and yields a tricoordinated intermediate complex (bI4). It was concluded, on the basis of structural and energetical properties of aI2 and bI4, that the second mechanism is significantly more favorable. It was shown that the oxidative addition requires noticeable lower activation energy than that required for the preactivation process. Thus, our investigations indicate that oxidative addition is not the rate determining step for the Heck reactions investigated in this work, but preactivation step.     

Controlled radical polymerization of cholesteryl acrylate and its block copolymer with styrene via the RAFT process

Reversible addition fragmentation chain transfer (RAFT) polymerization of cholesteryl acrylate (ChA) was conducted using S-1-dodecyl-S′-(α,α′-dimethyl-α′′-acetic acid)trithiocarbonate as CTA and AIBN as initiator in toluene at 80 °C. The polymerization was investigated at two different CTA concentrations (0.025 and 0.040 M). Polymerization of ChA with CTA concentration of 0.040 M proceeds in a controlled/living manner as evidenced by linear increase of the molecular weight with conversion and narrow polymer polydispersity (PDI < 1.2). With lower initial CTA concentration, namely 0.025 M, although poly(cholesteryl acrylate) (PChA) exhibiting narrow molecular weight distributions could be synthesized, the polymerization showed relatively low control with many termination products. Chain extension polymerizations were performed starting from either the PChA or the polystyrene (PS) block, and well-defined copolymers based on ChA and styrene were prepared. Thermal properties of PChA and PS-b-PChA copolymer were investigated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), and the results showed that both PChA and PS-b-PChA are amorphous polymers. PChA begins to decompose at ca. 218 °C with maximum weight loss rate at 351 °C, while PS-b-PChA shows double weight loss rate peaks located at 345 and 415 °C, respectively.     

Second-order calibration of excitation-emission matrix fluorescence spectra for determination of glutathione in human plasma

A rapid non-separative spectroflourimetric method based on the second-order calibration of the excitation-emission data matrix was proposed for the determination of glutathione (GSH) in human plasma. In the phosphate buffer solution of pH 8.0 GSH reacts with ortho-phthaldehyde (OPA) to yield a fluorescent adduct with maximum fluorescence intensity at about 420 nm. To handle the interfering effects of the OPA adducts with aminothiols other than GSH in plasma as well as intrinsic fluorescence of human plasma, parallel factor (PARAFAC) analysis as an efficient three-way calibration method was employed. In addition, to model the indirect interfering effect of the plasma matrix, PARAFAC was coupled with standard addition method. The two-component PARAFAC modeling of the excitation-emission matrix fluorescence spectra accurately resolved the excitation and emission spectra of GSH, plasma (or plasma constituents). The concentration-related PARAFAC score of GSH represented a linear correlation with the concentration of added GSH, similar to that is obtained in simple standard addition method. Using this standard addition curve, the GSH level in plasma was found to be 6.10 ± 1.37 μmol L⁻¹. The accuracy of the method was investigated by analysis of the plasma samples spiked with 1.0 μmol L⁻¹ of GSH and a recovery of 97.5% was obtained.     

A Facile Procedure for Conjugate Addition of Amines to Electron Deficient Alkenes with Metal Oxide as Catalyst

A novel efficient procedure has been developed for the conjugate addition of amines to electron deficient alkenes. A series of metal oxides was synthesized for catalyzing the conjugate addition of amines and alkenes. After optimizing the reaction conditions, SrO was chosen as the most efficient catalyst for the reactions. The results show that the catalyst is very efficient for the conjugate addition of amines to electron deficient alkenes with the excellent yields in several minutes. Operational simplicity...     

Synthetic Study of (−)‐Norzoanthamine: Construction of the ABC Ring Moiety

Throw your hat in the ring : A highly diastereoselective synthesis of the ABC rings of (?)‐norzoanthamine has been achieved starting from the (?)‐Hajos–Parrish ketone (see scheme). Three asymmetric quaternary carbon centers on the C ring were constructed by a 1,4‐addition, and an intramolecular Diels–Alder reaction provided a trans‐decalin scaffold on the AB rings.

     

Polyketide‐Chain Branching by an Enzymatic Michael Addition

A new “branch” for polyketide synthases was discovered in the biosynthesis of the antimitotic rhizoxin complex in the endofungal bacterium Burkholderia rhizoxinica. Genetic engineering and the structural elucidation of pathway intermediates revealed that a complex polyketide chain is branched at the β position by an unprecedented conjugate addition of an acetyl building block to an acryloyl precursor (see scheme).

     

Asymmetric Organocatalytic Domino Michael/Aldol Reactions: Enantioselective Synthesis of Chiral Cycloheptanones,Tetrahydrochromenones, and Polyfunctionalized Bicyclo[3.2.1]octanes

C′mon 1,2‐dione : A new diastereo‐ and enantioselective Lewis base catalyzed domino Michael/aldol reaction converts α,β‐unsaturated aldehydes and 1,2‐diones into chiral bicyclo[3.2.1]octane‐6‐carbaldehydes. The products are produced in good to excellent enantioselectivities (90–98 % ee) and can be transformed into bicyclic diols and triols. Additionally, a retro‐aldol cyclization provides access to valuable tetrahydrochromenones (see scheme).