To provide supporting evidence for the proposal that [Cu a Cu b (5)]PF6 is a trapped intermediate of the CuAAC reaction, we used DFT computational modelling (CAMB3LYP, Gaussian '09) to explore the reaction pathway by working back from the solid-state structure of [Cu a Cu b (5)]PF6 obtained by SCXRD (Figure ). In brief, scanning the C-N 1 and C-N 3 bond length allowed us to identify a transition state (TS-2) only in the former case. An IRC calculation confirmed that this first order saddle point links the product and intermediate Int-2, which contains a six-membered metallocycle as previously proposed in computational studies of the CuAAC reaction . Scanning the C-N 3 bond length allowed a transition state (TS-1) to be identified and, once again, IRC calculations showed that this first order saddle point links metallocycle Int-2 to Cu-acetylide Int-1. The initial study was performed in the gas phase using the 6-31G basis set and no dispersion correction. All structures were then reoptimized in solvent (THF, polarization continuum model), with or without dispersion correction (GD3BJ model). A single point calculation was also performed using the 6-31G+(d,p) basis set with both solvent and dispersion Although these calculations are necessarily preliminary -[Cu a Cu b (5)]PF6 is a large structure, and no conformational searches were performed due to the high computational cost of doing so at a reasonable level of theoryseveral general observations can be made. Firstly, in all cases the barrier from Int-1 to TS1 is calculated to be accessible, with values ranging between +43 kJmol -1 (gas phase, no dispersion) to as low as 15 kJmol -1 in THF (PCM) and with dispersion correction (GD3BJ). Secondly, this first step is predicted to be rate limiting; the calculated barrier from Int-1 to TS-2 is in all cases lower than that from Int-1 to TS-1, and in some cases this reaction is predicted to be essentially barrierless. We also confirmed that Int-1 and its precursor, [Cu(1)(3)] + are both reasonable intermediates for the reaction; in all cases the equilibria between [Cu(1)MeCN] + and [Cu(1)(3)] + , and [Cu(1)(3)] + and Int-1 were found to be accessible with the products either weakly disfavored or strongly favored, depending on the model used. Performing the same calculations for the formation of 4H revealed that the analogous monomeric pathway is also reasonable, albeit the barrier for the cyclisation step was found to be higher in all cases, as previously observed in modelling of the CuAAC reaction 5H, which was characterized by NMR, MS and SCXRD, proved to be surprisingly basic; simply washing a solution of the free ligand in CH2Cl2 with H2O resulting in a mixture of 5H and a new species that was confirmed to the protonated ligand by comparison with the product obtained if 5H was instead washed with 1 M NH4PF6(aq). The solid-state structure of 5H provides some rationale for the observed basicity. In the neutral state, the pyridine lone pairs of one ring interact with the weakly polarized C-H of the triazole ring and the other with a relatively unpolarized C-H of the axle pyridine unit. Similarly, the triazole lone pairs interact with the weakly polarized C-H units of the macrocycle ethylene glycol units. As with classical cryptands, there does not appear to be enough space to accommodate solvent molecules (e.g., H2O) that might provide more favorable non-covalent interactions. Indeed, the solid-state structure of 5H was not obtained with exclusion of moisture. Although it was not possible to unambiguously determine the position of the added proton in the solid-state structure of 5H2 + , the reorientation of one macrocycle such that the bipyridine N atoms are convergent with those of the pyridine-triazole unit of the axle suggests the proton is bound in this 4N cavity. The other macrocycle remains oriented such that its pyridine N atoms interact with the C-H of the triazole, which is expected to be further polarized by protonation. Based on these observations, it appears that the unexpected basicity of 5H is due to the poor solvation of the pyridine lone pairs and the lack of compensating strong intercomponent interactions.