Highlights• Classical steric clashes might have the same topological features as bonding interactions.• An AIL can be observed for highly attractive or repulsive interactions.• An AIL might be a result of either an inflow or outflow of density.• Locally accumulated density does not imply an attractive interaction or an inflow of density.• Nature of an interaction can change with molecular environment. Graphical abstract 2 AbstractNine kinds of inter-and intramolecular interactions were investigated by exploring the topology of electron density in the interatomic regions using standard protocols of QTAIM, IQA and NCI techniques as well as in-house developed cross-sections of the electron and deformation density distributions. The first four methods provide the properties of the resultant density distribution in a molecular system whereas the later illustrates the process, inflow or outflow of density from fragments to the interatomic region of an interaction on its formation in a molecular system. We used (i) the QTAIM-defined atomic interaction line, AIL (presence or absence), (ii) IQA-defined interaction energy, attractive to repulsive, (ii)  2 < 0 to  2 >0, or (iii) (r) > 0 to (r) < 0; hence, none of the topological indices used here, either separately or combined, can be used to definitely predict the (de)stabilizing nature of an interaction except highly repulsive ones for which the absence of AIL, interatomic density depletion and outflow of density on interaction formation are observed.

A method designed to investigate, on a fundamental level, the origin of relative stability of molecules (or molecular systems in general) using Be II complexes with nitrilotriacetic acid (NTA) and nitrilotri-3-propionic acid (NTPA) as a case study (this is the only known example where a metal ion forms stronger complex with NTPA) is described. It makes use of the primary (self-atomic and diatomic interaction) and molecular fragment energy terms as defined in the IQA/F (Interacting Quantum Atoms/Fragments) framework. An extensive classical-type investigation, focused on single descriptors (bond length, density at critical point, the size of metal ion or coordination ring, interaction energy between Be II and a donor atom, etc.) showed that it is not possible to explain the experimental trend. The proposed methodology is fundamentally different in that it accounts for the total energy contributions coming from all atoms of selected molecular fragments, and monitors changes in defined energy terms (e.g., fragment deformation, inter-and intra-fragment interaction) on complex formation. By decomposing combined energy terms we identified the origin of relative stability of Be II (NTA) and Be II (NTPA) complexes. We found that the sum of coordination bonds' strength, as measured by interaction energies between Be II ion and donor atoms, favours BeNTA but the binding energy of Be II ion to the entire ligand correlates well with experimental trend. Surprisingly, the origin of Be II (NTPA) being more stable is due to less severe repulsive interactions with the backbone of NTPA (C and H-atoms). This general purpose protocol can be employed not only to investigate the origin of relative stability of any molecular system (e.g., metal complexes) but, in principle, can be used as a predictive tool for, e.g., explaining reaction mechanism (transitional states).3

Relative stability of ZnII complexes with nitrilotriacetic acid (ZnNTA) and nitrilotri‐3‐propionic acid (ZnNTPA) was investigated. Classical analysis of individual interactions using local indices failed to explain the preferential formation of ZnNTA. This work shows that the preferential formation of ZnNTA is not due to the size of coordination five‐membered rings or the absence of the steric CH‐‐HC contacts, as commonly considered. By combining interacting quantum atoms/fragments, IQA/IQF‐defined properties implemented in the π‐FARMS (preorganized‐interacting fragment attributed relative molecular stability) method, (i) several measures of ZnII “affinity” to NTPA were shown to be consistently greater than to NTA and (ii) larger stability of ZnNTA was attributed to coordinated water molecules. Being smaller, NTA occupies less space around the metal center. This results in less destabilised ZnOH2 coordination bonds and preorganization energy of H2O fragments being smaller in ZnNTA. Only by summing preorganization energies (of ligand and water fragments) and binding energy between fragments (using π‐FARMS method) we recovered the experimental trend. Importantly, the fundamental origin of all major energy components controlling relative stability of metal complexes was pin‐pointed using the π‐FARMS method.

The preferred sites for the benzylation of adenine under basic conditions were proven to be the N9 and N3 positions. Formation of the N9‐benzyladenine product is favored in polar aprotic solvents, such as DMSO, whereas the proportion of N3‐benzyladenine formed increases as the proportion of polar protic solvents, such as water, increases. X‐ray crystal structures were obtained for both N9‐benzyladenine and N3‐benzyladenine. 1H‐13C HMBC NMR spectroscopy revealed diagnostic correlations used to assign the 1H and 13C NMR chemical shifts confirming that the solution structures in three different solvents were the same as the isolated crystals. 13C NMR assignment for N9‐benzyladenine, N3‐benzyladenine, and N7‐benzyladenine was confirmed by computation using ADF.