Chapter IV Structure-Property Relationships for Hetero- Complementary Hydrogen-Bonding Partners
4.3 Discussions
4.3.1 Insights into Hydrogen-Bonding-Based Complementary Association
polymers. These results clearly substantiate that when used in dendritic configurations, carboxyl/tertiary amine pair is suitable for building complementary pairs of telechelic associative polymers as mist-control additives for fuels.
binding strength.24,67 The pioneering work by the Jorgensen group on DNA nucleiobase pairs reveals the influence of D/A site arrangement on their binding strengths.68,69 They proposed that partially charged atoms involved in hydrogen bonding in one partner can electrostatically interact with those in the other, and they further described such interactions as secondary electrostatic interactions (SEIs), which can be either attractive or repulsive depending on the pattern of D/A arrangement; the hydrogen bonds between the two partners were referred to as primary interactions. In addition, they suggested that attractive SEIs can provide additional stabilization to primary hydrogen bonds, whereas repulsive SEIs destabilize them. Based upon the above hypotheses, the Jorgensen group postulated that having all the hydrogen-bond donor groups in one partner and all the hydrogen-bond acceptor groups in the other would be the site arrangement that produces the strongest binding, since under this circumstance all SEIs would be attractive and able to contribute to the binding strength. Although Jorgensen’s corollary has been criticized,70 it has been found in good agreement with general experimental trends in triple-hydrogen-bonding hetero-complementary association,8,11,71,72 and it has also been applied quantitatively in empirical methods for predicting the strengths of hetero- complementary associative pairs.67,73
Figure 4.18 illustrates all possible D/A site arrangements for triple-hydrogen- bonding hetero-complementary association, and their representative examples (including their Kasso values). Placing donors and acceptors in an alternating order (i.e., ADA-DAD, Figure 4.18 (a)) leads to 4 repulsive SEIs, and consequently the resultant value of Kasso
(~103 M-1 in CDCl3) is the lowest among the three.11 In the case of the AAD-DDA pattern (Figure 4.18 (b)), 2 attractive SEIs and 2 repulsive SEIs result from such an arrangement;
therefore, there is no net effect of SEIs on binding strength, which leads to an increase in Kasso by an order of magnitude (Kasso ~ 104 M-1).71 Having all the hydrogen-bond donor sites in one partner and all acceptor sites in the other, i.e., AAA-DDD (Figure 4.18 (c)), as suggested by Jorgensen as the most favorable arrangement, renders all of the 4 possible SEIs attractive, and thus leads to a remarkably high value of Kasso (~ 107 M-1 in CH2Cl2).8 The trend of Kasso clearly indicates the significance of SEIs in OHB-based hetero-complementary association. Sartorius and Schneider extended Jorgensen’s SEI analysis by establishing an empirical relationship to correlate the binding free energy of DNA nucleobases and synthetic hydrogen-bonding host-guest complexes in CHCl3 at 25oC (Gasso) with the D/A site arrangements of these natural/synthetic hetero- complementary associative pairs, in order to provide a semi-quantitative way to estimate the effects of SEIs on the strengths of hetero-complementary associations.73 They found that each primary interaction (i.e., hydrogen bond) contributes -7.9 kJ/mol to Gasso, while the contribution from each repulsive SEI is +2.9 kJ/mol, and that from each attractive SEI is -2.9 kJ/mol. For a set of 58 different complexes investigated in their work, the calculated values of Gasso based on the above linear relationship were in remarkably good agreement with experimentally observed values with an average difference of 1.7 kJ/mol (which corresponds to an average factor of 2 in Kasso value).
From the perspective of SEI analysis, inspection on THY/DAAP and HR/CA pairs provides insights into the relationship between their binding strengths and D/A site arrangements. As shown in Figures 4.18 (a) and 4.19 (a), both pairs are based on alternating placement of D and A sites (THY/DAAP: ADA-DAD; HR/CA: DADDAD- ADAADA); therefore, SEIs in both pairs are all repulsive, and THY/DAAP and HR/CA
have 4 and 8 repulsive SEIs, respectively. Based on Schneider’s empirical Gasso formula, the three hydrogen bonds in the THY/DAAP pair contribute -23.7 kJ/mol to Gasso, while the four repulsive SEIs contribute +11.6 kJ/mol. That is, the alternating D/A site arrangement ADA-DAD results in a staggering 48.9% loss of the binding free energy provided by the three hydrogen bonds between THY and DAAP. Similarly, the six hydrogen bonds in the HR/CA pair contribute -47.4 kJ/mol to Gasso, whereas the eight repulsive SEIs contribute +23.2 kJ/mol, which is also 48.9% of the contribution of the primary interactions. The estimated values of net Gasso for THY/DAP and HR/CA pairs, -12.1 and 24.2 kJ/mol respectively, can be converted to their Kasso in CHCl3 at 25oC using the following thermodynamic relationship:
RT
Kasso exp Gasso
The calculated values of Kasso for THY/DAAP and HR/CA based on Schneider’s empirical formula are 1.48 × 102 and 2.21× 104 M-1, respectively, and both are in good agreement with literature data (Table 4.1).
The above analysis on THY/DAAP and HR/CA pairs implicates a dilemma concerning the development of telechelic associative polymers as mist-control additives for kerosene using OHB-based hetero-complementary associative pairs as polymer end- groups. The MCK application demands for an inexpensive polymer formulation that imposes minimum increase on fuel cost, and thus complementary associative pairs that can be easily synthesized and attached to polymer chain ends, such as THY/DAAP and HR/CA, are preferred in this regard. The problem is, however, that they are both plagued by the reduction of association strength by repulsive SEIs resulting from the alternating
D/A site arrangement, which explains the finding that the HR/CA pair failed to enable the formation of supramolecular aggregates of telechelic 1,4-PB chains of Mw ~ 200 kg/mol stable at low-moderate shear rates (Figure 4.14). An OHB-based hetero- complementary associative pair stronger than HR/CA is therefore needed. Ideally, a D/A site arrangement that results in less or even no repulsive SEIs, for instance, ADDA- DAAD and AAAA-DDDD, would generate complementary association stronger than that of HR/CA. A representative example of the former pattern is the UG/DAN pair (Table 4.1 and Figure 4.19 (b)), in which there are 4 primary interactions, 2 attractive SEIs, and 4 repulsive SEIs. That is, the overall contribution of SEIs to the binding strength is 2 repulsive SEIs, which is significantly less than that in HR/CA (8 repulsive SEIs). The estimated Gasso and Kasso in CHCl3 at 25oC for the UG/DAN pair, based on Schneider’s empirical formula, are -26.2 kJ/mol and 3.89×104 M-1 respectively, and these values are in good agreement with the literature.21 The calculated results also explain why the quadruple-hydrogen-bonding UG/DAN pair is stronger than the sextuple-hydrogen- bonding HR/CA pair. The problem is, however, that the synthesis of DAN unit requires the use of very expensive starting material (2,7-di-chloronathyridine), palladium catalyst, and multiple cycles of chromatographic separation that counterbalance the benefit of strength provided by the UG/DAN pair.13,14,74,75 The issue of synthetic accessibility is even worse in the case of the ideal AAAA-DDDD pattern, and it can be illustrated by the hetero-complementary associative pair synthesized by Blight and coworkers (Figure 4.19 (c)).72 Although the AAAA-DDDD pattern results in six attractive SEIs that contribute considerably to the overall binding strength and leads to an exceptionally high Kasso (>
3×1012 M-1 in CH2Cl2 at 25oC), these AAAA and DDDD clusters are prohibitively
complicated and costly to synthesize (a problem shared by the triple-hydrogen-bonding AAA-DDD pair), and it is even harder to prepare them in asymmetric forms that can be further functionalized and used as polymer end-groups. In addition, the fused heterocyclic structure of the DDDD cluster has been found photochemically unstable.
The trade-off between binding strength and synthetic accessibility renders it difficult to implement multiple OHB-based hetero-complementary associations in the development of mist-control polymers for fuels.
On the other hand, CAHB-based DA/DB and TA/TB pairs both present a much greater feasibility compared to the multiple OHB-based complementary associative pairs in Figure 4.19. The superior strength of the CAHB between carboxyl and tertiary amine groups, which is nearly 4 times as strong as OHBs such as NH···O and NH···N, provides a convenient way to pack plenty of strength into a compact configuration. To illustrate, the binding strength of the structure-wise simple DA/DB pair is roughly equivalent to that provided by 8 OHBs, and the TA/TB pair could deliver a strength equivalent to nearly 16 OHBs. Therefore, we can rank the strength of the four hetero-complementary associative pairs investigated in the present study as follows:
TA/TB > DA/DB > HR/CA >THY/DAAP
The design of dendritic end-groups we developed (Schemes 2.1 and 4.1) provides an inexpensive, simple and effective synthetic route to precisely control the number of CAHBs included in the carboxyl/tertiary-amine complementary end-association of telechelic 1,4-PB chains. Having all carboxyl groups on one dendritic end group and all tertiary-amine groups on the other also suggests the absence of repulsive SEIs. The shear viscosity data of HR/CA and DA/DB pairs reflect the superiority of CAHB-based design
(Figures 4.13 and 4.14): While the HR/CA pair failed to provide enough strength to hold polymer chains of Mw ~ 200 kg/mol together as supramolecules stable at low shear rates, the elegantly simple DA/DB pair was found effective in driving these polymer chains to form supramolecular aggregates stable at moderate shear rates. The above comparison also implicates that an OHB-based hetero-complementary associative pair that contains 8 OHBs and has a D/A site arrangement free of repulsive SEIs may possess sufficient binding strength for affording supramolecules stable at shear rates relevant to the MCK application. The problem is, however, that it is already difficult enough to synthesize an array of hydrogen-bond acceptors containing 4 acceptor sites and to use it as a polymer end group.72 To double the number of acceptors from 4 to 8 is a daunting task, and the accompanying cost and instability issues would further render the implementation of OHB-based hetero-complementary association in the development of mist-control polymers for fuels impractical.