An electron density (ED)-based methodology is developed for the automatic identification of intermolecular interactions using pro-molecular density. The expression of the ED gradient in terms of atomic components furnishes the basis for the Independent Gradient Model (IGM). This model leads to a density reference for non interacting atoms/fragments where the atomic densities are added whilst their interaction turns off. Founded on this ED reference function that features an exponential decay also in interference regions, IGM model provides a way to identify and quantify the net ED gradient attenuation due to interactions. Using an intra/inter uncoupling scheme, a descriptor (δg) is then derived that uniquely defines intermolecular interaction regions. An attractive feature of the IGM methodology is to provide a workflow that automatically generates data composed solely of intermolecular interactions for drawing the corresponding 3D isosurface representations.

Extraction of the chemical interaction signature from local descriptors based on electron density (ED) is still a fruitful field of development in chemical interpretation. In a previous work that used promolecular ED (frozen ED), the new descriptor, δg , was defined. It represents the difference between a virtual upper limit of the ED gradient (∇ρIGM , IGM=independent gradient model) that represents a noninteracting system and the true ED gradient (∇ρ ). It can be seen as a measure of electron sharing brought by ED contragradience. A compelling feature of this model is to provide an automatic workflow that extracts the signature of interactions between selected groups of atoms. As with the noncovalent interaction (NCI) approach, it provides chemists with a visual understanding of the interactions present in chemical systems. ∇ρIGM is achieved simply by using absolute values upon summing the individual gradient contributions that make up the total ED gradient. Hereby, we extend this model to relaxed ED calculated from a wave function. To this end, we formulated gradient-based partitioning (GBP) to assess the contribution of each orbital to the total ED gradient. We highlight these new possibilities across two prototypical examples of organic chemistry: the unconventional hexamethylbenzene dication, with a hexa-coordinated carbon atom, and β-thioaminoacrolein. It will be shown how a bond-by-bond picture can be obtained from a wave function, which opens the way to monitor specific interactions along reaction paths.

The design of novel stimuli-responsive supramolecular systems based on host− guest chemistry implies a thorough understanding of the noncovalent interactions involved. In this regard, some computational tools enabling the extraction of the noncovalent signatures from local descriptors based on the electron density have been previously proposed. Although very useful to detect the existence of such interactions, these analyses provide only a semi-quantitative description, which represents a limitation. In this work, we present a novel computational tool based on the local atomic descriptor IGM-δg inter/At , which is able to decompose the fragment interaction into atomic contributions. Then, the role played by each atom in the formation of the host−guest assembly is quantified by an integrated Δg inter/At score. Herein, we apply the IGM-Δg inter/At approach to some challenging systems, including multimetallic arrays, buckycatchers, and organic assemblies. These systems exhibit unique structural features that make it difficult to determine the host/guest atoms that contribute the most to the guest encapsulation. Here, the Δg inter/At score proves to be an appealing tool to shed light on the guest accommodation on a per-atom basis and could be useful in the rational design of more selective target agents. We strongly believe that this novel approach will be useful for experimental teams devoted to the synthesis of supramolecular systems based on host−guest chemistry.

The photochemically induced intramolecular hydrogen abstraction or hydrogen atom transfer in cyclic imines 8a,b followed by a cyclization is investigated. Two types of products are observed, one resulting from the formation of a C-C bond, the other from the formation of a C-N bond. A computational study reveals that hydrogen is exclusively transferred to the imine nitrogen leading to a triplet diradical intermediate. After intersystem crossing, the resulting zwitterionic intermediate undergoes cyclization leading to the final product.

Heterocyclic compounds play an important role in many domains of chemistry. They are important structural elements in bioactive compounds. Photochemical reactions enable transformations of such compounds in a very convenient way. In many cases no chemical reagent is used. Members of one compound family can be transformed into members of another one. Three important types of photochemical rearrangements with heterocyclic compounds are discussed: Photochemical heteroatom isomerization involving heteroatoms and substituents, photochemical reactions involving hydrogen atom transfer (HAT) and photochemical electrocyclization.

Many photochemical reactions are carried out under particular sustainable conditions. Often no chemical activation is necessary and the photon is considered as a traceless reagent. These reactions give access to unusual molecular structures and therefore are highly appreciated for application to organic synthesis, especially in heterocyclic chemistry. In this context, photochemical position isomerizations of heterocyclic compounds are discussed. Photochemical rearrangements induced by electron and hydrogen atom transfer (HAT) are also used for the preparation of heterocyclic compounds. Photochemical electrocyclization is discussed with sixmembered heterocycles such as pyridine derivatives. Finally, photochemically induced cyclization are presented as a very suitable method for the construction of heterocycles. The synthesis of biologically active compounds is particularly focused. Thus perspectives of sustainable chemistry are presented for the pharmaceutical and agrochemical industry.

The Front Cover shows the stereo and regio selective addition of radical species such as alkyl or formamidyl radicals to levoglucosenone. Levoglucosenone is a biobased platform chemical obtained from celluloses. The radical intermediates are generated by hydrogen atom transfer involving photocatalysis with tetra‐n‐butylammonium decatungstate (TBADT). Cover picture created with the help of Tony Leclet. More information can be found in the Article by N. Hoffmann et al.

We hereby introduce the atomic Degree Of Interaction (DOI), a new concept rooted in the electron density-based Independent Gradient Model (IGM). Capturing any manifestation of electron density sharing around an...