The Energetics of Intramolecular Halogen Bond Formation Using Aryldiyne Linkers

Transcription

1 The Energetics of ntramolecular alogen Bond ormation Using Aryldiyne Linkers Sierra M. Giebel, Dr. athan P. Bowling, and Dr. Erin D. Speetzen University of Wisconsin- Stevens Point

2 What is a halogen bond? UPAC definition - A halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. This electrophilic region of the halogen is referred to as the s - hole. highlights/1445- halogen- bond- catalysis- in- silico- design

3 actors Affecting alogen Bond Strength - Directionality 180 o - X.. Y- X =, Cl, Br, Y =, O, X -, etc, The angle between the halogen bond donor (X) and the halogen bond acceptor (a lone pair on Y) should be as close to 180 o as possible

4 actors Affecting alogen Bond Strength dentity of X eview hers feature axial XBs are dotted e; iodine, purple; toms are omitted the disorder on igure 16. Molecular electrostatic potential at the isodensity surface with au for C4, C3Cl, C3Br, and C3. Color ranges: red, greater than 27 kcal/mol; yellow, between 20 and 14 kcal/mol; green, 12 and 6 kcal/mol; blue, negative. Adapted with permission Cavallo ebetween t a l, C hem. ev , 116, from ref 145. Copyright Springer. The larger the s - hole (shown in red) the stronger the halogen bond. n general the strength of the halogen bond changes as > Br > Cl >

5 actors Affecting alogen Bond Strength ybridization The greater the s character in an sp- hybridized carbon the better its electron- withdrawing ability. As the s- character of the carbon attached to the halogen increases, so does the strength of the halogen bond. C(sp) X > C(sp 2 ) X > C(sp 3 ) X. diiodoacetylene and (bromoethyny

6 actors Affecting alogen Bond Strength Substitution Cl Cl E XB = kcal/mol Br E XB = kcal/mol Br E XB = kcal/mol E XB = kcal/mol Use of electron withdrawing substituents on the atoms attached to the donor can increase the size of the s - hole, leading to stronger halogen bond. E XB = kcal/mol E XB = kcal/mol Tsuzuki, et al., Chem. Eur. J. 2012, 18,

7 Thermodynamics of alogen Bond ormation Br Br D = kcal/mol D = kcal/mol D = 9.92 kcal/mol TD S = kcal/mol TD S = kcal/mol TD S = kcal/mol D G = 5.11 kcal/mol D G = kcal/mol D G = 2.60 kcal/mol Since halogen bonds are relatively weak, entropy effects can easily overwhelm the favorable enthalpy change upon halogen bond formation. esults of M062X calculations using 6-31G* on, C,,, and Br and cc- pvdz- PP on

8 Previous esearch Cl Br The Bowling group at UW- SP has shown previously that aryldiyne linkers can be used to overcome the unfavorable entropy associated with halogen bond formation and form intramolecular halogen bonded complexes in solution and in the crystal phase.

9 Current esearch Br Br The Bowling group is currently investigating whether the same aryldiyne linker that was used on perfluoro compounds 1 and 2 can be used to examine halogen bonding in weaker, non- activated halogen bonding systems, such as 3 and 4.

10 Experimental esults Both solution- and crystallographic studies showed the formation of a halogen bond in the activated (perfluoro) systems, but no evidence of halogen bond formation was found in solution studies in the non- activated systems. Crystal structures of the non activated systems indicated the formation of halogen bonded dimers. To help understand this, the Speetzen group was asked to do calculations on the energetics associated with forming these halogen bonds.

11 Computational Systems The model compounds shown here were used. While chlorine was not used as a halogen bond donor in the experimental work it was used in the computational work. Br Cl All structures (unless otherwise noted) were optimized at the M062X level of theory using the 6-31G* basis set for all atoms, except, for which the cc- pvdz basis set and corresponding pseudo potential were used Single point energies were carried out at the M062X/def2TZVP level of theory, unless otherwise noted. Br Cl

12 Estimation of intramolecular halogen bond energy or an intermolecular halogen bond, calculation of the halogen bond strength (E XB ) is straightforward + ragment 1 ragment 2 Complex E XB = E complex (E frag1 + E frag2 ) or an intramolecular halogen bond, it is impossible to separate the strength of the halogen bond from the total energy of the system. But, one can approximate it using methods such as the Molecular Tailoring Approach (MTA).

13 Molecular Tailoring Approach The molecular tailoring approach was developed to estimate the strength of intramolecular hydrogen bonds. t is a fragmentation- based method in which the system of interest (M) is partitioned into a series of fragments: one in which the donor is removed (M1), one in which the acceptor is removed (M2), and one in which both have been removed (M3). The intramolecular hydrogen bond strength (E B ) is then estimated as usinska- oszak and Sowinski J. Chem. nf. Model 2014, 54, E B = E M1 + E M2 E M3 - E M

14 MTA ntermolecular alogen Bond Partitioning X = Cl, Br, or = or M1 X MX X M2 To verify that the MTA method would work for halogen bonding we tested it on an intermolecular system first. We chose a fictitious system that was similar to the intramolecular one we were interested in. The structure of interest (MX) was optimized, and the fragments were generated by removing the donor ring, acceptor ring, or both and capping the cut bond with a at a fixed distance of 1.0 Angstroms. M3 E XB = E M1 + E M2 E M3 - E MX

15 MTA ntermolecular alogen Bond esults Br Cl Br Cl E XB Actual 4.08 kcal/mol 2.21 kcal/mol 1.53 kcal/mol 6.20 kcal/mol 3.70 kcal/mol 2.75 kcal/mol E XB MTA 4.07 kcal/mol 2.43 kcal/mol 1.39 kcal/mol 6.05 kcal/mol 3.77 kcal/mol 2.44 kcal/mol % Error 0.3% 10.2% 9.4% 2.3% 2.0% 11.1% Errors ranged from 0.3% to 11.1% indicating that the molecular tailoring approach should give sufficient accuracy for our purpose.

16 MTA ntermolecular alogen Bond Partitioning X X = Cl, Br, or = or MX X The intramolecular halogen- bonded systems were fragmented according to the scheme shown. The same computational methods were used as with the intermolecular test systems. M1 M2 M3 E XB (=(E M1 (+(E M2 (+(E MX (+(E M3

17 MTA ntermolecular alogen Bond esults Br Cl Br Cl E XB MTA 5.68 kcal/mol 3.42 kcal/mol 2.22 kcal/mol 3.75 kcal/mol 2.09 kcal/mol 1.14 kcal/mol As expected the halogen bond strength for the activated (perfluoro) systems is higher than for the non- activated systems. owever, the halogen bond strength for the non- activated iodo system (3.75 kcal/mol) is predicted the be very similar to the energy of the activated bromo system (3.42 kcal/mol). The former is not observed to halogen bond in solution, while the latter is. To explain this one must look at other factors involved in halogen bond formation.

18 Deformation upon halogen bond formation n both crystal structures and computational structures, there is evidence that the alkynes must bend in order to accommodate formation of the halogen bond. To estimate the energy associated with this process the following method was used. X eplace X with in the optimized structure D E = E deform X = Cl, Br, or = or

19 Deformation Energy esults Br Cl Br Cl E XB MTA 5.68 kcal/mol 3.42 kcal/mol 2.22 kcal/mol 3.75 kcal/mol 2.09 kcal/mol 1.14 kcal/mol E deform 0.75 kcal/mol 0.29 kcal/mol 0.18 kcal/mol 0.60 kcal/mol 0.20 kcal/mol 0.10 kcal/mol As expected as the size of the halogen decreases E deform decreases. As expected as the strength of the halogen bond decreases for the same halogen, E deform decreases. E deform is slightly larger for the non- activated iodo complex compared to the activated bromo complex (0.60 kcal/mol vs 0.29 kcal/mol).

20 otational Barrier Since crystal structures showed that in the non- activated systems, the donor ring had rotated, leading to the formation of halogen bonded dimers, the energies associated with rotation of that ring were also examined. The donor ring was rotated in increments of 5 degrees while the rest of the molecule was allowed to relax. Addition angles were included as needed. Since the halogen bond was being broken, all optimizations were carried out using the 6-31+G* basis set for all atoms but iodine, for which the aug- cc- pvtz basis set and pseudopotential were used.

21 otational Barrier esults so ar D E (kcal/mol) Br - Activated - on- Activated - Activated ing Angle (degrees) We see a lower rotational barrier for the non activated iodo system compared the activated iodo system. There are a number of data points still missing for the activated bromo system that make comparing to the iodo systems difficult.

22 Conclusions and uture Work We have used computational chemistry to estimate The strength of intramolecular halogen bonds The deformation energy upon halogen bond formation The rotational barrier to break the halogen bond for a series of model compounds. At this point we do not have enough data to explain the experimental results. We need to complete the relaxed scans and carry out higher level single point calculations on the resulting structures before attempting to draw any conclusions from that data.

23 Acknowledgements Dr. athan Bowling and the Bowling esearch Group, particularly Danielle Widner, Emily obinson, Alejandra Perez, erh Vang, achel Thorson, and Zakarias Driscoll. Dr. Eric Bosch for crystal structures Computational resources provided by S- M awards #CE and #CE through the Midwest Undergraduate Computational Chemistry Consortium- - MU3C.