Electronic control of product distribution in the [5+5]-coupling of ortho-alkynylbenzaldehyde derivatives and γ,δ-unsaturated carbene complexes

The coupling of highly oxygenated ortho-alkynylbenzaldehyde derivatives with γ,δ-carbene complexes was evaluated systematically. In all of the electron-rich systems investigated the exclusive product of the reaction is the dihydrophenanthrene derivative. Only the extremely electron-withdrawing methanesulfonate group can prevent this process from occurring. The use of the base additive collidine resulted in a surprising yield enhancement but no other discernable effect on the course of the reaction. Dihydrophenanthrene formation was attributed to rapid dehydration after the opening of a benzo-oxanorbornene intermediate.     

Dissolved organic carbon--contaminant interaction descriptors found by 3D force field calculations

Enthalpies of transfer at 300 K of various partitioning processes were calculated in order to study the suitability of 3D force fields for the calculation of partitioning constants. A 3D fulvic acid (FA) model of dissolved organic carbon (DOC) was built in a MM+ force field using AMI atomic charges and geometrical optimization (GO). 3,5-Dichlorobiphenyl (PCB14), 4,4'-dichlorobiphenyl (PCB15), 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane (PPDDT) and 2-chloro-4-ethylamino-6-isopropylamino-s-triazine (Atrazine) were inserted into different sites and their interaction energies with FA were calculated. Energies of hydration were calculated and subtracted from FA-contaminant interactions of selected sites. The resulting values for the enthalpies of transfer from water to DOC were 2.8, -1.4, -6.4 and 0.0 kcal/mol for PCB 14, PCB15, PPDDT and Atrazine, respectively. The value of PPDDT compared favorably with the experimental value of -5.0 kcal/mol. Prior to this, the method was studied by the calculation of the enthalpies of vaporization and aqueous solution using various force fields. In the MM + force field GO predicted enthalpies of vaporization deviated by +0.7 (PCB14), +3.6 (PCB15) and -0.7 (PPDDT)kcal/mol from experimental data, whereas enthalpies of aqueous solution deviated by -3.6 (PCB14), +5.8 (PCB15) and +3.7 (PPDDT) kcal/mol. Only for PCB14 the wrong sign of this enthalpy value was predicted. Potential advantages and limitations of the approach were discussed.     

The transfer between instruments of a reflectance near-infrared assay for paracetamol in intact tablets

This study compares several correction methods to facilitate the transfer of a validated near-infrared (NIR) assay for paracetamol in intact tablets between two reflectance NIR instruments of the same type. Transfer was defined as the ability to accurately predict the true assay value of a sample measured on a NIR system using an assay developed on a different system, and was assessed using a comprehensive set of statistical tests. Direct electronic transfer of the calibration models, representing the NIR assay, was not possible as a result of a definite residual spectrum between instruments. The use of a correction method based on the standardisation of the material used to record the reference spectrum also proved ineffective. Two methods investigated did succeed, the first employed a response surface calculated between the reflectance values of a set of six certified photometric standards measured on both instruments, with all full range partial least square (PLS) regression models subsequently transferred. The next was correction of the spectra from the second instrument utilising the residual spectrum between the mean sample of the validation set measured on both instruments. Through this approach all PLS regression models and also a single multiple linear regression (MLR) model were transferred. As an outcome of this study guidelines are suggested for the transfer of NIR assays along with the criteria deemed necessary to conclusively prove transfer and justify any correction method utilised. The significant criteria were determined to be the paired t-test with both the UV reference assay data and the original NIR assay data, and comparison of the coefficient of multiple determinations.