Article Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis Magnus Blom 1, Sara Norrehed 1, Claes-Henrik Andersson 1, Hao Huang 1, Mark E. Light 2, Jonas Bergquist 1, Helena Grennberg 1 and Adolf Gogoll 1,* Received: 25 October 2015 ; Accepted: 7 December 2015 ; Published: 23 December 2015 Academic Editor: M. Graça P. M. S. Neves 1 Department of Chemistry-BMC, Uppsala University, Uppsala S-75123, Sweden; [email protected] (M.B.); [email protected] (S.N.); [email protected] (C.-H.A.); [email protected] (H.H.); [email protected] (J.B.); [email protected] (H.G.) 2 Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK; [email protected] * Correspondence: [email protected]; Tel.: +46-184-713-822 Abstract: Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar enediyne (1), the helical stiff stilbene (2), or the semi-rigid glycoluril motif fused to the porphyrins (3), are compared. Binding 4 6 ´1 constants Ka = 10 –10 M reveal subtle differences between these tweezers, that are discussed in terms of porphyrin dislocation modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis. Keywords: bisporphyrin tweezers; metalloporphyrins; porphyrinoids; host-guest chemistry; supramolecular chemistry; chirogenesis; chirality transfer; exciton coupled circular dichroism; conformational analysis 1. Introduction Bisporphyrin molecular clips and tweezers are well studied systems for ditopic host–guest interactions [1,2]. In the majority of these compounds, two porphyrin chromophores are attached by a single bond to a usually conformationally flexible spacer. They have been used extensively to determine the absolute configuration of guests with a single stereogenic center, or to distinguish enantiomers [3–15]. We recently have shown that bisporphyrin tweezers also can be utilized for determination of the relative stereochemistry in molecules with several stereocenters, employing a semi-rigid bisporphyrin tweezer 3 incorporating a glycoluril spacer [16,17]. For further investigations, we required alternative tweezers with altered conformational flexibility, a key factor for guest affinity. Also, substitutes for 3 requiring a less demanding synthetic protocol are desirable. Therefore, we decided to replace the glycoluril spacer with enediyne and stiff stilbene spacers, respectively (Figure1). These tweezers are expected to have restricted conformational flexibility, comparable to other tweezers with spacers composed of aromatic rings and ethyne segments [1]. Since several parameters are involved in host–guest binding, accurate predictions of ligand affinity are not always possible. However, bisporphyrins with flexible spacers are capable of strong binding to dinitrogen ligands. In typical examples, small aliphatic diamines were found to bind with 3 5 ´1 Ka = 10 –10 M to a bisporphyrin with diphenylether spacer, with weaker binding for bulkier guests [5]. Much higher binding constants have been reported for the structurally more rigid DABCO Molecules 2016, 21, 16; doi:10.3390/molecules21010016 www.mdpi.com/journal/molecules Molecules 2016, 21, 16 2 of 24 Molecules 2016, 21, 0016 7 9 ´1 2 of 24 (diazabicyclo[2.2.2]octane) with Ka = 10 –10 M [18,19]. The variation of binding constants with spacer length and flexibility has been explained by preorganization effects when binding rigid Ka = 107–109 M−1 [18,19]. The variation of binding constants with spacer length and flexibility has been guestsexplained [20]. by preorganization effects when binding rigid guests [20]. 1 2 3 Figure 1. Bisporphyrin molecular tweezers with enediyne (1) and stiff stilbene (2) spacers, and the Figure 1. Bisporphyrin molecular tweezers with enediyne (1) and stiff stilbene (2) spacers, and the previously reported semi-rigid 3 with glycoluril spacer. previously reported semi-rigid (3) with glycoluril spacer. Bisporphyrin tweezers have been classified as belonging to three distinct categories regarding Bisporphyrinthe conformational tweezers properties have of been their classifiedspacers: spac asers belonging with high to conformational three distinct flexibility, categories spacers regarding the conformationalwith conformational properties restrictions of their, and spacers: conformationally spacers withrigid highspacers conformational [1]. Rigid spacers flexibility, may favor spacers withguest conformational binding due restrictions, to a preorganization and conformationally effect, but also prevent rigid spacers binding [1 of]. Rigidguests spacersthat cannot may be favor accommodated by bitopic binding [21]. Flexible spacers allow more diverse binding via an induced guest binding due to a preorganization effect, but also prevent binding of guests that cannot be fit [22–24]. The three bisporphyrins 1–3 discussed here present a more subtle conformational behavior. accommodatedIn principle, by bitopic four different binding types [21 ].of Flexible dislocation spacers of the allowtwo porphyrin more diverse units, some binding of which via an might induced fit [22be–24 interdependent,]. The three bisporphyrins may be distinguished1–3 discussed (Figure here2). present a more subtle conformational behavior. In principle,For the previously four different studied types glycoluril of dislocation bisporphyrin of the tweezer two porphyrin3, we have observed units, some conformational of which might be interdependent,flexibility in terms may of be interporphyrin distinguished distance (Figure 2variation). (Figure 2a), due to the conformational Forproperties the previously of the glycoluril studied spacer glycoluril [16]. bisporphyrinThis manifested tweezer itself experimentally3, we have observed in variation conformational of the flexibilityhydrodynamic in terms of radius interporphyrin of the tweezer distance upon binding variation of (Figurevarious2 guests,a), due as to monitored the conformational by the diffusion properties of thecoefficient glycoluril of spacerthe host-guest [16]. This complex. manifested However, itself since experimentally the porphyrin inunits variation are attached of the to hydrodynamicthe spacer radiusvia of two the covalent tweezer bonds, upon lateral binding dislocation of various (Figure guests, 2b) appears as monitored to be unlikely, by the diffusionand porphyrin coefficient rotation of the (Figure 2d) is impossible. There is, however, an option of porphyrin twisting (Figure 2c) via host-guest complex. However, since the porphyrin units are attached to the spacer via two covalent conformational changes of the seven-membered rings in the glycoluril backbone (vide infra). bonds,In contrast, lateral dislocation both 1 and 2 (Figure might allow2b) appears for lateral to dislocation be unlikely, as well and as porphyrin twisting as rotation the result (Figure of spacer2d) is impossible.bond distortion, There is, in however, combination an option with po ofrphyrin porphyrin rotation twisting around (Figure single bonds.2c) via conformational changes of the seven-memberedIt occurred to us ringsthat detection in the glycoluril of the induced backbone circular (vide dichroism infra). ( Ini.e. contrast,, exciton coupled both 1 andcircular2 might allowdichroism, for lateral ECCD) dislocation [3–15] asthat well results as twisting from binding as the a result chiral ofdiamine spacer guest bond might distortion, provide in a combination simple withexperimental porphyrin rotation verification around of the single distortion bonds. modes available to our tweezers (Table 1). Tweezer Itflexibility occurred and to guest us that geometry detection determine of the the induced sign and circular amplitude dichroism of the detected (i.e., exciton ECCD, coupledand suitable circular dichroism,mnemonics ECCD) for reliable [3–15] prediction that results of the from effect binding are still a under chiral development diamine guest [8,9]. might The effect provide of rigidity a simple experimentalvariation verificationon CD performance of the distortion has been modesaddressed available for chiral to ourbisporphyrin tweezers tweezers (Table1). without Tweezer bound flexibility and guest geometry determine the sign and amplitude of the detected ECCD, and suitable mnemonics for reliable prediction of the effect are still under2 development [8,9]. The effect of rigidity variation on CD performance has been addressed for chiral bisporphyrin tweezers without bound guests [25], Molecules 2016, 21, 16 3 of 24 Molecules 2016, 21, 0016 3 of 24 whereas we here investigate achiral bisporphyrin tweezers. Recently, Rath and co-workers have shown that chirogenesisguests [25], in whereas a bisporphyrin we here investigate tweezers achiral requires bisporphyrin porphyrin tweezers. twisting Recently, [ 26Rath]. and co-workers have shown that chirogenesis in a bisporphyrin tweezers requires porphyrin twisting [26]. (a) distance variation (b) lateral dislocation (c) porphyrin twisting (d) porphyrin rotation Figure 2. Possible dislocations in bisporphyrin tweezers: (a) Variation of interporphyrin distance; Figure 2. (Possibleb) lateral displacement; dislocations (c) inporphyrin bisporphyrin twisting; ( tweezers:d) porphyrin (rotation.a) Variation