To find the validity of the results of this study we thought of using this MEPS outcome in predicting the structural outcome of the reported crystal structures. A comprehensive CSD search was carried out targeting the halogen-bond donors utilized in this study and the outcome was seventeen suitable structures where an asymmetric acceptor with two or more acceptor sites are present. Lack of structural data based on halogen bond studies with asymmetric acceptor sites further enhances the importance of this study. The group of acceptors contained ditopic as well as multitopic acceptors and also acceptors based on N, O and S giving exposure to a diverse group. MEPS calculations on these selected systems were carried out and results are summarized in the Table 4.4.
According to this analysis the predicted outcome from the ΔE value based system is in agreement with the actual structural outcome for fourteen of seventeen structures leading to the prediction success of 82%. This success rate underscores the importance of such a simple method based on easily accessible MEPS calculations in designing halogen-bond based molecular recognition studies.
Table 4.4 Results comparison for CSD reported structures
Donor CSD code Best acceptor Electrostatic potentials (kJ/mol) 2nd best acceptor ΔE value (kJ/mol) Predicted outcome Structural outcome
D1 ULOKOV -160 -41 119
Preferred for
best acceptor best acceptor Preferred for
ULOLAI -164 -152 12 No preference No preference
D2 BEWXOS -175 -154 21 No preference No preference
D3
BEWXIM -175 -154 21 No preference No preference
COKNOG -171 -58 113 best acceptor Preferred for best acceptor Preferred for
D4
COKNUM -171 -58 113 best acceptor Preferred for best acceptor Preferred for ECASAE -182 -150 32 No preference best acceptor Preferred for
D6 D7
D8
COGKAM -164 -30 134 best acceptor Preferred for best acceptor Preferred for
DIVCIV -152 -108 44 Grey region No preference
KABLAC -174 -30 144 best acceptor Preferred for best acceptor Preferred for JAQMEU -191 -145 46 Grey region best acceptor Preferred for LUKMIN -137 -102 53 Grey region best acceptor Preferred for PEFPAT -212 -57 155 best acceptor Preferred for best acceptor Preferred for QOLJIK -142 -106 36 Grey region best acceptor Preferred for TOJBUQ -178 -174 4 No preference best acceptor Preferred for
TOJCAX -195 -155 40 Grey region No preference
VABNUJ -175 -149 26 No preference Binds to 2acceptor nd best
D9 D10
4.5 Conclusions
A systematic co-crystallization study was carried out between twelve asymmetric ditopic acceptors and nine halogen-bond donors (108 experiments) in order to identify halogen bond selectivity depending on the MEPS difference between the two acceptor sites. 36 crystal structures were obtained and together with three structures from the CSD lead to the identification of three categories based on halogen bond selectivity, Figure 4.16. If the ΔE value is less than 35 kJ/mol, there is no halogen bond selectivity. In the intermediate region (35 kJ/mol < ΔE < 65 kJ/mol), no prediction can be made. This is recognized as the grey area. If the ΔE value is more than 65 kJ/mol, then the halogen bond is selective for the best acceptor site as ranked by electrostatics. These results provide a set of guidelines which can be utilized in designing more complex supramolecular architectures with halogen bonding, but further studies based on different donor acceptor systems are required for the compilation of well-defined rules for halogen bond binding preferences.
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