Energies for the cocrystal interconversion reactions calculated from periodic DFT and calorimetry data, as well as experimental outcomes of the corresponding mechanochemical transformations. The average differences between the energies calculated with two DFT methods are: MAE 2.1 kJ mol⁻¹; RMSD 2.2 kJ mol⁻¹.

Reaction Nr	Reaction type	Reaction equation	ΔE/kJ mol−1			Experimental LAG reactions (forward/reverse)
			PBE + D3	PBE + MBD*	Experimental calorimetry	Ethanol	Aceto-nitrile	Hexane
1	Acceptor exchange	(pyr)1/2(tftib) + 2,2′-bipy → (2,2′-bipy)(tftib) + 1/2 pyr	−3.4	−4.7	−5.7(8)	Forward	Forward	Forwarda
2		(pyr)1/2(tftib) + 4,4′-bipy → (4,4′-bipy) (tftib) + 1/2 pyr	−18.4	−20.1	−13.2(6)	Forward	Forward	Forward
3		(pyr)1/2(tftib) + dabco → (dabco)(tftib) + 1/2 pyr	−22.3	−18.3	−10.0(8)	Forward	Forward	Forwarda
4		(pyr)1/2(tftib) + acr → (acr) (tftib) + 1/2 pyr	−1.0	0.2	0.4(5)	Forward	Forward	Forwardb
5		(pyr)1/2(tftib) + tmpyr → (tmpyr)(tftib) + 1/2 pyr	−8.1	−6.0	−7.1(7)	Forward	Forward	Forward
6	Donor exchange	(pyr)1/2(tftib) + ½ 14tfib → 1/2 (pyr)(14tfib) + tftib	0.3	−1.4	0.6(7)	Reverse	Reverse	Reverse
7		(pyr)1/2(tftib) + 1/2 fum → 1/2 (pyr)(fum) + tftib	6.9	5.1	4.2(5)	Reverse	Reverse	Reverse
8		(pyr)1/2(tftib) + 1/2 pht → 1/2 (pyr)(pht) + tftib	12.3	9.5	6.8(7)	Reverse	Reverse	Reverse
9		(pyr)1/2(tftib) + tdec → 1/2 (pyr) (tdec)2 + tftib	6.1	9.2	4.7(8)	Reverse	Reverse	Reversec
10		(pyr)1/2(tftib) + 1/2 succ → 1/2 (pyr)(succ) + tftib	7.3	5.5	1.3(1)	Reverse	Reverse	Reversec
11		(pyr)1/2(tftib) + 1/2 ox → 1/2 (pyr)(ox) + tftib	−3.6	−5.1	−1.8(5)	Forward	Forward	Forward

^aReaction proceeds with a solvated intermediate.

^bLAG reactions result in a mixture of (pyr)_1/2(tftib) and (acr)(tftib), upon storage the proportion of (acr)(tftib) in the reaction mixture increases (ESI Fig. S6 and S7).

^cLAG reactions result in a mixture of (pyr)_1/2(tftib) and product cocrystal for the corresponding reaction, but full conversion to the product cocrystal is observed upon storing the samples at room temperature up to 3 months.