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In this study, the ability of beryllium compounds to establish π-hole bonding interactions has been evaluated at the RI-MP2/def2-TZVPD level of theory. A search of the Protein Data Bank revealed some X-ray crystal structures in which BeF3− moieties act as electron-acceptor entities. We have used [Mg(BeF3)(HCOO)] ( 1) as a π-hole bond donor and CO, CH3CN, NH3, O(CH3)2, S(CH3)2, H3PO, and glycine as electron-rich entities. In all cases, favorable binding energies were obtained, reflecting the attractive nature of the interaction involving the trivalent beryllium atom (-BeF3 moiety). In addition, we have used Bader's theory of 'atoms in molecules' and noncovalent interaction (NCI) plot analysis to further investigate and characterize the π-hole complexes described herein. To the best of our knowledge, π-hole interactions involving beryllium have not hitherto been described in the literature. [ABSTRACT FROM AUTHOR]

High-level calculations (RI-MP2/def2-TZVP) disclosed that the σ-hole in between two C atoms of cycloalkane X2CCX2 structures (X=F, CN) is increasingly exposed with decreasing ring size. The interacting energy of complexes of F−, HO−, N≡C−, and H2CO with cyclopropane and cyclobutane X2CCX2 derivatives was calculated. For X=F, these energies are small to positive, while for X=CN they are all negative, ranging from −6.8 to −42.3 kcal mol−1. These finding are corroborated by a thorough statistical survey of the Cambridge Structural Database (CSD). No clear evidence could be found in support of non-covalent carbon bonding between electron-rich atoms (El.R.) and F2CCF2 structures. In marked contrast, El.R.⋅⋅⋅(CN)2CC(CN)2 interactions are abundant and highly directional. Based on these findings, the hydrophobic electrophilic bowl formed by 1,1′,2,2′-tetracyano cyclopropane or cyclobutane derivatives is proposed as a new and synthetically accessible supramolecular synthon. [ABSTRACT FROM AUTHOR]

The glyoxylate shunt is an anaplerotic bypass of the traditional Krebs cycle. It plays a prominent role in Mycobacterium tuberculosis virulence, so it can be exploited for the development of antitubercular therapeutics. The shunt involves two enzymes: isocitrate lyase (ICL) and malate synthase (GlcB). The shunt bypasses two steps of the tricarboxylic acid cycle, allowing the incorporation of carbon, and thus, refilling oxaloacetate under carbon-limiting conditions. The targeting of ICL is complicated; however, GlcB, which accommodates the pantothenate tail of acetyl-CoA in the active site, is easier to target. A catalytic Mg2+ unit is located at the bottom of the cavity, and plays a very important role. Recently, the development of effective antituberculosis drugs based on phenyldiketo acids (PDKAs) has been reported. Interestingly, all the crystal structures of GlcB-inhibitor complexes exhibit close contact between the carboxylate of Asp633 and the face of the aromatic ring of the inhibitor. Remarkably, the replacement of the phenyl ring in PDKA by aliphatic moieties yields inactive inhibitors, suggesting that the aromatic moiety is crucial for inhibition. However, the aromatic ring of PDKA is not electron-deficient, and consequently, the anion-π interaction is expected to be very weak (dominated only by polarization effects). Herein, through a combination analysis of the recent X-ray structures of GlcB-PDKA complexes retrieved from the protein data bank (PDB) and computational ab initio studies (RI-MP2/def2-TZVP level of theory), we demonstrate the prominent role of the Mg2+ ion in the active site, which promotes long-range enhancement of the anion-π interaction. [ABSTRACT FROM AUTHOR]