A Thermally Populated, Perpendicularly Twisted Alkene Triplet Diradical.

Variable-temperature NMR and ESR spectroscopic studies reveal that bis(dibenzo[a,i]fluorenylidene) 1 possesses a singlet ground state, 1(S0 ), while the 90° twisted triplet 1(T1 ) is populated to a small extent already at room temperature. Analysis of the increasing amount of paramagnetic 1(T1 ) at temperatures between 300 and 500 K yields the exchange interaction Jex /h c=3351 cm-1 and a singlet-triplet energy splitting of 9.6 kcal mol-1 , which is in excellent agreement with calculations (9.3 kcal mol-1 at the UKS BP86/B3LYP/revPBE level of theory). In contrast, the zero-field splitting parameter D is very small (calculated value -0.018 cm-1 ) and unmeasurable.

Laser-induced carbene-carbene rearrangement in solution: the diphenylcarbene-fluorene rearrangement.

Diphenylcarbene (DPC) generated by high-intensity laser photolysis of diphenyldiazomethane rearranges to fluorene (FL) by two distinct mechanisms as revealed by methyl-group labeling. Thus, excimer laser irradiation of p,p'-dimethyldiphenyldiazomethane generates 3,6-dimethylfluorene (3,6-DMF) and 2,7-dimethylfluorene (2,7-DMF), which were identified by fluorescence measurements as well as GC-MS and comparison with authentic materials. 3,6-DMF corresponds to direct bond formation between ortho positions in DPC, referred to as ortho,ortho' coupling. 2,7-DMF corresponds to a carbene-carbene rearrangement, whereby DPC undergoes ring expansion to phenylcycloheptatetraene (PhCHT) followed by ring contraction to o-biphenylylcarbene (o-BPC), which then cyclizes to FL. The carbene-carbene rearrangement dominates over the ortho,ortho' coupling under all conditions employed. The ortho,ortho' coupling must take place in a higher excited state (most likely S2 or T1) of DPC, because it is not observed at all under thermolysis conditions, where only S1 and T0 are populated. The carbene-carbene rearrangement may take place either in a hot S1 state or more likely in a higher excited state (S2 or T1).

Standardisation and international adoption of defined approaches for skin sensitisation.

In the absence of stand-alone one-to-one replacements for existing animal tests, efforts were made to integrate data from in silico, in chemico and in vitro methods to ensure sufficient mechanistic coverage of the skin sensitisation Adverse Outcome Pathway (AOP) and generate predictions suitable for hazard identification and potency sub-categorisation. A number of defined approaches (DAs), using fixed data interpretation procedures (DIP) to integrate data from multiple non-animal information sources, were proposed and documented using a standard reporting template developed by the Organisation for Economic Co-operation and Development (OECD). Subsequent international activities focused on the extensive characterisation of three of these DAs with respect to the reference in vivo data, applicability domains, limitations, predictive performances and characterisations of the level of confidence associated with the predictions. The ultimate product of this project was an OECD Guideline that provides information equivalent to that provided by the animal studies and that can be used to satisfy countries' regulatory data requirements for skin sensitisation. This Defined Approach Guideline was the first of its kind for the OECD, and provides an important precedent for regulatory adoption of human biology-relevant new approach methodologies with performances equivalent to, or better than, traditional animal tests. This mini review summarizes the principal features of the defined approaches described in OECD guideline 497.