SACs) (see also reviews [11][12][13] ). SACs could offer ultimate atom economy and make every active site accessible, like homogeneous catalysts but being recyclable, which is a subject of paramount importance. [14] Major challenges in the field though encompass: i) the development of materials with precise functionalities for robust metal ion binding and ii) metal cooperativity in heterometallic and mixed-valence SACs, as identified in the recent topical perspective. [12] Meeting the first challenge could facilitate higher metal contents avoiding clustering and leaching upon reaction and catalyst recycling. This is also a prerequisite for the second challenge (metal-metal cooperation), since low metal content translates into large intermetallic distances. [6] Cooperation between two metal ions linked by a single-frame ligand has shown enormous potential in homogeneous catalysis. [15] For example, biocatalysts (metalloenzymes) use binuclear [16] and mixed-valence metal centers [17] for effective catalysis. Therefore, the development of heterogeneous catalysts with cooperativity between metal centers, keeping all the salient features of SACs, could offer a platform for the development of the next generation of catalysts.Graphene-based 2D materials have contributed to the development of SACs, [10,[12][13][14][18][19][20][21][22][23][24][25][26][27] in which metal ions are tetracoordinated in porphyrinic-like vacancies. Although only low contents of metal atoms can be achieved (up to ≈1 wt%), [10,12,14,18,[22][23][24][25][26] Single-atom catalysts (SACs) aim at bridging the gap between homogeneous and heterogeneous catalysis. The challenge is the development of materials with ligands enabling coordination of metal atoms in different valencestates, and preventing leaching or nanoparticle formation. Graphene functionalized with nitrile groups (cyanographene) is herein employed for the robust coordination of Cu(II) ions, which are partially reduced to Cu(I) due to graphene-induced charge transfer. Inspired by nature's selection of Cu(I) in enzymes for oxygen activation, this 2D mixed-valence SAC performs flawlessly in two O 2 -mediated reactions: the oxidative coupling of amines and the oxidation of benzylic CH bonds toward high-value pharmaceutical synthons. High conversions (up to 98%), selectivities (up to 99%), and recyclability are attained with very low metal loadings in the reaction. The synergistic effect of Cu(II) and Cu(I) is the essential part in the reaction mechanism. The developed strategy opens the door to a broad portfolio of other SACs via their coordination to various functional groups of graphene, as demonstrated by successful entrapment of Fe III /Fe II single atoms to carboxy-graphene. Single-Atom CatalysisThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201900323.

Given its five unpaired d-electrons, long electronic relaxation time, and fast water exchange, Mn(2+) is a potential candidate for contrast agent application in medical magnetic resonance imaging. Nevertheless, the design of chelators that ensure stable Mn(2+) complexation and optimal relaxation properties remains a coordination chemistry challenge. Here, we report the synthesis of two pyridine-containing ligands L1 and L2, with 15-membered triaza-dioxa-crown and pentaaza-crown ether macrocycles, respectively, and the characterization of their Mn(2+) complexes. Protonation constants of the ligands and stability constants of various metal complexes were determined by potentiometry. The presence of the pyridine in the macrocyclic ring induces rigidity of the complexes which results in a greater thermodynamic stability with respect to the nonpyridine analogues. Solid-state structures of MnL1 and MnL2 confirmed seven-coordination of Mn(2+) with Cl(-) and H(2)O in axial positions. The dissociation kinetics of MnL2 in the presence of Zn(2+) were followed by relaxometric measurements. They proved the prime importance of the proton-assisted dissociation while the zinc(II)-assisted pathway is not important at physiological pH. For MnL1, the dissociation was too fast to be studied by conventional relaxivity measurements under pH 6. A combined (17)O NMR and (1)H NMRD study on MnL1 and MnL2 yielded the parameters that govern the relaxivity of these complexes. The water exchange rate for MnL1, k(ex)(298) = 0.38 x 10(7) s(-1), is the lowest value ever reported for a Mn(2+) complex, while a considerably higher value was obtained for MnL2 (k(ex)(298) = 6.9 x 10(7) s(-1)). Anion binding was studied by relaxometric titrations. They revealed weak interactions between MnL2 and phosphate or citrate, leading to the formation of monohydrated species. Overall, the incorporation of a pyridine into a polyaza macrocycle scaffold has several beneficial effects on the Mn(2+) chelates with respect to potential MRI contrast agent applications: (i) The thermodynamic and the kinetic stability of the complexes is increased. (ii) The rigidified ligand backbone results in higher coordination numbers of the metal ion, allowing for two inner-sphere water molecules in aqueous solution.

Mn2+ has five unpaired d electrons, a long electronic relaxation time, and labile water exchange, which make it an attractive alternative to Gd3+ in the design of contrast agents for medical Magnetic Resonance Imaging. In order to ensure in vivo safety and high contrast agent efficiency, the Mn2+ ion has to be chelated by a ligand that provides high thermodynamic stability and kinetic inertness of the complex and has to have at least one free coordination site for a water molecule. Unfortunately, these two requirements are contradictory, as lower denticity of the ligands, which leads to more inner‐sphere water molecules often implies a decreased stability of the complex, and, therefore, it is necessary to find a balance between both requirements. In the last decade, a large amount of experimental data has been collected to characterize the physico‐chemical properties of Mn2+ chelates with variable ligand structures. They now allow for establishing trends of how the ligand structure, the rigidity of the ligand scaffold, and its donor–acceptor properties influence the thermodynamic, kinetic, and redox stability of the Mn2+ complex. This microreview surveys the current literature in this field.