Fluorinated porphyrin tweezer: a powerful reporter of absolute configuration for erythro and threo diols, amino alcohols, and diamines

A general and sensitive nonempirical protocol to determine the absolute configurations of erythro and threo diols, amino alcohols, and diamines is reported. Binding of diols to the porphyrin tweezer system is greatly enhanced by increasing the Lewis acidity of the metalloporphyrin. Supramolecular complexes formed between the porphyrin tweezer host and chiral substrates exhibited exciton-coupled bisignate CD spectra with predictable signs based on the substituents on the chiral center. The working model suggests that the observed helicity of the porphyrin tweezer is dictated via steric differentiation experienced by the porphyrin ring bound to each chiral center. A variety of erythro and threo substrates were investigated to verify this chiroptical method. Their absolute configurations were unequivocally determined, and thus a general mnemonic is provided for the assignment of chirality.     

Chiral recognition by CD-sensitive dimeric zinc porphyrin host. 2. Structural studies of host-guest complexes with chiral alcohol and monoamine conjugates.

A structural study of complexes formed between a dimeric zinc porphyrin tweezer (host) and chiral monoalcohols and monoamines derivatized by a bidentate carrier molecule (guest) confirmed that their CD couplets arise from the preferred porphyrin helicity of 1:1 host-guest complexes. NMR experiments and molecular modeling of selected tweezer complexes revealed that the preferred conformation is the one in which the L (larger) group protrudes from the porphyrin sandwich; this preferred helicity of the complex determines the CD of the complexes. It was found that the porphyrin ring-current induced (1)H chemical shifts and molecular modeling studies of the complex lead to the assignments of relative steric size of the L (large)/M (medium) substituents attached to the stereogenic center. The assignments, in turn, are correlated with the sign of the CD exciton couplet that establishes the absolute configuration at the stereogenic center. Variable-temperature NMR experiments proved that the observed increase in CD amplitude at lower temperatures derives from conformational changes in the preferred offset geometry between two porphyrin rings.     

From supramolecular porphyrin tweezers to dynamic A(n)B(m)C(l)D(k) multiporphyrin arrangements through orthogonal coordination

A dynamic, supramolecular, three-component A(n)B(m)C(l) bis(zinc porphyrin) tweezer has been prepared quantitatively using the heteroleptic bisphenanthroline (HETPHEN) concept. Upon addition of nitrogenous spacers of different length, namely, the extended bipyridine 3 a, 4,4'-bipyridine (3 b), and 1,4-diazabicyclo[2.2.2]octane (DABCO; 3 c), to set up an additional orthogonal binding motif (Zn(Por)-N(spacer)), three structurally different, still dynamic, four-component A(n)B(m)C(l)D(k) assemblies were cleanly formed, as indicated by UV/Vis and NMR titrations as well as by DOSY investigations. The structures were identified as a bridged monotweezer A(2)BC(2)D, a doubly bridged double tweezer A(4)B(2)C(4)D(2), and a triply bridged double tweezer A(4)B(2)C(4)D(3), the latter resembling a porphyrin stack. Notably, the same structures were equally formed directly from a mixture of the constituents A, B, C, and D put together in any sequence if the correct stoichiometry was applied.     

Sensing Remote Chirality: Stereochemical Determination of β‐, γ‐, and δ‐Chiral Carboxylic Acids

Determining the absolute stereochemisty of small molecules bearing remote nonfunctionalizable stereocenters is a challenging task. Presented is a solution in which appropriately substituted bis(porphyrin) tweezers are used. Complexation of a suitably derivatized β‐, γ‐, or δ‐chiral carboxylic acid to the tweezer induces a predictable helicity of the bis(porphyrin), which is detected as a bisignate Cotton Effect (ECCD). The sign of the ECCD curve is correlated with the absolute stereochemistry of the substrate based on the derived working mnemonics in a predictable manner.     

Dynamic Assembly Inclusion Complexes of Tweezer‐type Bis(zinc porphyrin) with 5,15‐Di(4‐pyridyl)porphyrin Derivatives

Dynamic assembly inclusion complexes of tweezer-type bis(zinc porphyrin) (1) with di(4-pyridyl)porphyrin derivatives have been designed and constructed. The complexes are induced by Zn-N coordination, and the weak binding allows the large-size di(4-pyridyl)porphyrin guests in random rotation. Dynamic characteristics of these assemblies, such as ligand exchange and dynamic fluorescence quenching, have been investigated by 1H NMR, UV-Vis and fluorescence spectra. The stability of such assembly has pronounced dependence on the size-matching effect and thermal effect.     

Supramolecular chirogenesis in zinc porphyrins: interaction with bidentate ligands,formation of tweezer structures,and the origin of enhanced optical activity

The complexation behavior, binding properties, and spectral parameters of supramolecular chirality induction in the achiral host molecule, syn (face-to-face conformation) ethane-bridged bis(zinc porphyrin), upon interaction with chiral bidentate guests (diamines and amino alcohols) have been studied by means of UV-vis, CD, fluorescence, (1)H NMR, and ESI MS techniques. It was found that the guest structure plays a decisive role in the chirogenesis pathway. The majority of bidentate ligands (except those geometrically unsuitable) exhibit two major equilibria steps: the first guest ligation leading to formation of the 1:1 host-guest tweezer structure (K(1)) and the second guest molecule ligation (K(2)) forming the anti bis-ligated species (1:2). The second ligation is much weaker (K(1) > K(2)) due to the optimal geometry and stability of the 1:1 tweezer complex. The enhanced conformational stability of the tweezer complex ensures an efficient chirality transfer from the chiral guest to the achiral host, consequently inducing a remarkably high optical activity in the bis-porphyrin.     

Hydrogen bonding-driven elastic bis(zinc)porphyrin receptors for neutral and cationic electron-deficient guests with a sandwich-styled complexing pattern

This Letter reports the design and synthesis of a new type of hydrogen bonding-mediated foldamer-derived tweezer receptors that are incorporated with two peripheral (zinc)porphyrin units. Due to the existence of four intramolecular hydrogen bonds, the (zinc)porphyrin units are forced to approach and stack with each other. ¹H NMR and fluorescent studies revealed that the new receptors could form 1:1 complexes with planar electron-deficient molecules such as naphthalene and benzene diimides and paraquat through a unique sandwich-styled binding pattern. The association constants of the new complexes have been evaluated by the ¹H NMR or fluorescent titration methods.     

3]rotaxane-porphyrin conjugate as a novel supramolecular host for fullerenes

A new supramolecular host with good affinity toward fullerenes has been developed. This host having a tweezer-like shape is built on a [3]rotaxane scaffold and contains two free-base porphyrin moieties as recognition units for fullerenes. The ability of this tweezer to bind fullerenes strongly depends on the solvent system used and the size of fullerene.     

Anion directed synthesis of paddlane and trisilver tweezer complexes based upon silver coordination chemistry

Addition of AgBF4 or Ag(O3SCF3) to the tripodal ligand, Me3tacnRh(CCPh)3, yields a paddlane complex as well as a novel trinuclear silver "tweezer" complex based upon silver acetylene coordination chemistry. The paddlane is composed of two Me3tacnRh(CCPh)3 moieties held together by silver acetylene interactions. The tweezer complex is composed of one tripodal moiety with three silver atoms coordinated to each acetylene-Rh-acetylene face. The tweezer complex is stabilized by additional interactions, including a triflate anion which serves to cap the complex.     

Prompt determination of absolute configuration for epoxy alcohols via exciton chirality protocol

A microscale protocol for determination of absolute configurations of 2,3-epoxy alcohols is described. 2,3-Disubstituted (cis and trans), 2,2-disubstituted, 2,2,3-trisubstituted, and 2,3,3-trisubstituted epoxy alcohols rendered prominent ECCD signals upon complexing with a Lewis acidic porphyrin tweezer and consequently provide straightforward assignment of chirality for epoxy alcohols. This method proved to be rapid, simple, sensitive, and reliable for the class of molecules listed above.     

Synthesis and Complexation Studies of a Convex Bis-porphyrin Tweezer—A Molecular Capsule Precursor

The synthesis and spectroscopic studies of a convex bis-porphyrin based molecular tweezer are reported. The complexation of small bidentate ligands by metallated derivatives of the bis-porphyrin host were monitored through UV–visible and ¹H NMR spectroscopy and yielded large association constants.     

Chiral recognition by CD-sensitive dimeric zinc porphyrin host. 1. Chiroptical protocol for absolute configurational assignments of monoalcohols and primary monoamines.

A general microscale protocol for the determination of absolute configurations of primary amino groups or secondary hydroxyl groups linked to a single stereogenic center is described. The chiral substrates are linked to the achiral trifunctional bidentate carrier molecule (3-aminopropylamino)acetic acid (1, H(2)NCH(2)CH(2)CH(2)NHCH(2)COOH) and the resultant conjugates are then complexed with dimeric zinc porphyrin host 2 giving rise to 1:1 host/guest sandwiched complexes. These complexes exhibit exciton-coupled bisignate CD spectra due to stereodifferentiation leading to preferred porphyrin helicity. Since the chiral sense of twist between the two porphyrins in the complex is dictated by the stereogenic center of the substrate, the sign of the couplet determines the absolute configuration at this center. The twist of the porphyrin tweezer in the complex can be predicted from the relative steric sizes of the groups flanking the stereogenic center, such that the bulkier group protrudes from the complex sandwich. In certain alpha-hydroxy esters and alpha-amino esters, electronic factors and hydrogen bonding govern the preferred conformation of the complex, and hence the CD spectra.     

A chemo-mechanical tweezer for single-molecular characterization of soft materials

A new atomic force microscopy (AFM)-based chemo-mechanical tweezer has been developed that can measure mechanical properties of individual macromolecules in supramolecular assembly and reveal positions of azide-containing polymers. A key feature of the new technology is the use of an AFM tip densely modified with 4-dibenzocyclooctynols (chemo-mechanical tweezer) that can react with multiple azide containing macromolecules of micelles to give triazole "clicked" compounds, which during retracting phases of AFM imaging are removed from the macromolecular assembly thereby providing a surface topographical image and positions of azide-containing polymers. The force-distance curves gave mechanical properties of removal of individual molecules from a supramolecular assembly. The new chemo-mechanical tweezer will make it possible to characterize molecular details of macromolecular assemblies thereby offering new avenues to tailor properties of such assemblies.     

Magnesium tetraarylporphyrin tweezer: a CD-sensitive host for absolute configurational assignments of alpha-chiral carboxylic acids

A protocol to determine the absolute configuration of alpha-chiral carboxylic acids based on a modified circular dichroic (CD) exciton chirality method has been developed. The protocol relies on a host-guest complexation mechanism: the chiral substrates are derivatized to give bifunctional amide conjugates ("guests") that form complexes with a dimeric magnesium porphyrin host, Mg-T (T stands for "tweezer") that acts as a "receptor". The two porphyrins in the complex adopt a preferred helicity dictated by the substituents at the chiral center in accordance with their steric sizes (assigned on the basis of conformational energy A-values) and, consequently, with the absolute configuration of the substrates under investigation. This chiroptical method, verified with a variety of chiral substrates, has been demonstrated to be reliable and generally applicable, including natural products with complex structures. Molecular modeling, NMR, and FTIR experiments of selected host-guest complexes revealed the mode of ligation of the substrates to the magnesium porphyrin species and led to clarification of the structure of the complex. When oxygen functionalities were directly attached to the chiral center, the signs of the CD couplets were opposite to those predicted on the basis of steric size. NMR and molecular modeling experiments indicated that this apparent inconsistency was due to conformational characteristics of the guest molecules. The stereochemical analysis is shown to be a sensitive technique, not only for the determination of absolute configurations of substrates but also for elucidation of their solution conformations.     

Molecular tweezer based on zinc porphyrin-substituted diarylethene

A molecular tweezer, zinc porphyrin-dithienylethene-zinc porphyrin (ZnP-DTE-ZnP) triad, has been prepared. Triad ZnPor-DTE-ZnPor showed a little electronic communication among the chromophores judged from the comparison of the steady-state absorption and fluorescence spectra for triads and their component compounds. Irradiation of ZnPor-DTE-ZnPor with UV light converts dithienylethene moiety from open form to closed form. The complexation of ZnP-DTE-ZnP with 4,4'-bipyridyl were investigated by absorption and fluorescence spectroscopic measurements. ZnP-DTE-ZnP forms a 1:1 complex with 4,4'-bipyridyl. The stability constants of log K=4.0 and 4.2 mol(-1)dm3 were determined by absorption and fluorescence spectral changes, respectively.     

Foldamer-based pyridine-fullerene tweezer receptors for enhanced binding of zinc porphyrin

This paper reports the design and synthesis of a new series of hydrogen bonding-mediated foldamer-derived tweezer receptors that are used for efficient complexation of zinc porphyrin guest. One end of the rigidified aromatic amide backbone is incorporated with one fullerene unit, while another end is connected to one pyridine or imidazole unit. The ¹H NMR, UV-vis, and fluorescent investigations in chloroform revealed that, due to the intramolecular hydrogen bonding-driven preorganized folded conformation, the fullerene and pyridine units of the receptors are located with suitable spatial separation and consequently able to co-complex zinc porphyrin with remarkably increased stability. In contrast, the imidazole-incorporated receptor displays a weakened binding affinity possibly due to structural mismatching and large steric hindrance. The association constants of the complexes of the new receptors with zinc porphyrin have been determined.     

Absolute configurational assignments of secondary amines by CD-sensitive dimeric zinc porphyrin host

A general chiroptical protocol for determination of absolute configuration of secondary amines including acyclic and cyclic aliphatic amines, aromatic amines, amino acids, and amino alcohols is described. The chiral substrate is linked to the achiral carrier moiety (3-N-Boc-amino-propyl-N-Boc-amino)acetic acid 1 (BocHNCH(2)CH(2)CH(2)BocNCH(2)COOH), which after deprotection, yields a bidentate conjugate, capable of forming a 1:1 host/guest complex with dimeric zinc porphyrin host 2. As in the cases of primary amines and secondary alcohols reported earlier, the complexation of secondary amine conjugates to porphyrin tweezer host 2 represents a stereodifferentiating process, where the large (L) group at the stereogenic center (assigned on the basis of conformational energies A value) protrudes from the porphyrin binding pocket. This leads to formation of host/guest complexes with a preferred porphyrin helicity that exhibit intense exciton split CD spectra. It was found that the chiral sense of porphyrin twist is clearly controlled by the stereogenic center despite the Z/E conformational complexity around the tertiary amide bond of secondary amine conjugates that has greatly hampered previous configurational assignments. Thus, in cases where there is no ambiguity regarding the relative steric size of substituents, the observed CD couplet can be applied for straightforward assignment of absolute configurations. In addition, to extend the application to more difficult cases a molecular mechanics calculation approach using the Merck Molecular Force Field (MMFFs) was developed; this provides conformational information of host/guest complexes and leads to prediction of preferred porphyrin helicity independent of conformational A values. This chiroptical protocol in combination with molecular modeling represents a general method for configurational assignments of secondary amines.     

Sterically controlled recognition of macromolecular sequence information by molecular tweezers

Sequence-specific binding is demonstrated between pyrene-based tweezer molecules and soluble, high molar mass copolyimides. The binding involves complementary pi-pi stacking interactions, polymer chain-folding, and hydrogen bonding and is extremely sensitive to the steric environment around the pyromellitimide binding-site. A detailed picture of the intermolecular interactions involved has been obtained through single-crystal X-ray studies of tweezer complexes with model diimides. Ring-current magnetic shielding of polyimide protons by the pyrene "arms" of the tweezer molecule induces large complexation shifts of the corresponding 1H NMR resonances, enabling specific triplet sequences to be identified by their complexation shifts. Extended comonomer sequences (triplets of triplets in which the monomer residues differ only by the presence or absence of a methyl group) can be "read" by a mechanism which involves multiple binding of tweezer molecules to adjacent diimide residues within the copolymer chain. The adjacent-binding model for sequence recognition has been validated by two conceptually different sets of tweezer binding experiments. One approach compares sequence-recognition events for copolyimides having either restricted or unrestricted triple-triplet sequences, and the other makes use of copolymers containing both strongly binding and completely nonbinding diimide residues. In all cases the nature and relative proportions of triple-triplet sequences predicted by the adjacent-binding model are fully consistent with the observed 1H NMR data.     

Synthesis of guanidinium-derived receptor libraries and screening for selective peptide receptors in water

A library of "tweezer" receptors, incorporating a guanidinium "head group" and two peptide derived side arms has been prepared on the solid-phase using an orthogonally protected guanidinium scaffold 12. The library was screened with various tripeptide derivatives in an aqueous solvent system. A tweezer receptor 25 for the side chain protected tripeptide 19 was identified from the screening experiments. Receptor 25 was resynthesised and solution binding studies were carried out, which revealed that 25 binds to tripeptide 19 with K(a)=8.2 x 10(4) +/- 2.5 x 10(4) (15 % DMSO/H(2)O, pH 8.75) and with appreciable selectivity over the tripeptide enantiomer 22 and the side chain deprotected tripeptide 20.     

Extreme complementarity in a macrocycle-tweezer complex

[reaction: see text] Interaction of a novel pyrene-based tweezer molecule with a macrocyclic ether-imide-sulfone results in formation of a strongly bound complex (K(a) = 24 000 M(-)(1)) in which binding results not only from pi-pi stacking interactions involving pyrene units as donors and macrocyclic naphthalene-tetracarboximide and biphenylenedisulfone groups as acceptors but also from N-H.O and C-H.O hydrogen bonds and from "reverse" pi-stacking of the electron-poor isophthaloyl residue of the tweezer with an electron-rich 3-aminophenoxy residue of the macrocyclic imide.