Controlling the length of porphyrin supramolecular polymers via coupled equilibria and dilution-induced supramolecular polymerization

Multi-component systems often display convoluted behavior, pathway complexity and coupled equilibria. In recent years, several ways to control complex systems by manipulating the subtle balances of interaction energies between the individual components have been explored and thereby shifting the equilibrium between different aggregate states. Here we show the enantioselective chain-capping and dilution-induced supramolecular polymerization with a Zn2+-porphyrin-based supramolecular system when going from long, highly cooperative supramolecular polymers to short, disordered aggregates by adding a monotopic Mn3+-porphyrin monomer. When mixing the zinc and manganese centered monomers, the Mn3+-porphyrins act as chain-cappers for Zn2+-porphyrin supramolecular polymers, effectively hindering growth of the copolymer and reducing the length. Upon dilution, the interaction between chain-capper and monomers weakens as the equilibria shift and long supramolecular polymers form again. This dynamic modulation of aggregate morphology and length is achieved through enantioselectivity in the aggregation pathways and concentration-sensitive equilibria. All-atom and coarse-grained molecular simulations provide further insights into the mixing of the species and their exchange dynamics. Our combined experimental and theoretical approach allows for precise control of molecular self-assembly and chiral discrimination in complex systems.

Proving Nanoscale Chiral Interactions of Cyclodextrins and Propranolol Enantiomers by Means of SERS Measurements Performed on a Solid Plasmonic Substrate

Chiral separation is an important issue for the pharmaceutical industry. Over the years, several separation methods have been developed, mainly based on chromatography. Their working principle is based on the formation of transient diastereoisomers, but the very subtle nanoscale interactions responsible for separation are not always understood. Recently, Raman and surface-enhanced Raman (SERS) spectroscopy have provided promising results in this field. Here we present Raman/SERS experimental data that provide useful information concerning the nanoscale interactions between propranolol enantiomers and α, β, and γ cyclodextrins. Raman spectroscopy was used to prove the formation of host–guest intermolecular complexes having different geometries of interaction. The occurrence of new vibrational bands and a change in the intensities of others are direct proofs of complexes’ formation. These observations were confirmed by DFT calculations. By performing SERS measurements on a new type of plasmonic substrate, we were able to prove the intermolecular interactions responsible for PRNL discrimination. It turned out that the interaction strength between the substrate and the intermolecular complexes is of paramount importance for SERS-based chiral discrimination. This approach could represent a very good starting point for the evaluation of molecular interactions manifesting between other pharmaceutical compounds and different classes of chiral selectors.

Asymmetric Total Syntheses of Both Enantiomers of Plymuthipyranone B and Its Unnatural Analogues: Evaluation of anti-MRSA Activity and Its Chiral Discrimination

Chiral total syntheses of both enantiomers of the anti-MRSA active plymuthipyranone B and all of the both enantiomers of three unnatural and synthetic analogues were performed. These two pairs of four chiral compounds are composed of the same 3-acyl-5,6-dihydro-2H-pyran-2-one structure. The starting synthetic step utilized a privileged asymmetric Mukaiyama aldol addition using Ti(OiPr)4/(S)-BINOL or Ti(OiPr)4/(R)-BINOL catalysis to afford the corresponding (R)- and (S)-δ-hydroxy-β-ketoesters, respectively, with highly enantiomeric excess (>98%). Conventional lactone formation and successive EDCI-mediated C-acylation produced the desired products, (R)- and (S)-plymuthipyranones B and three (R)- and (S)- synthetic analogues, with an overall yield of 42–56% with a highly enantiomeric excess (95–99%). A bioassay of the anti-MRSA activity against ATCC 43300 and 33591 revealed that (i) the MICs of the synthetic analogues against ATCC 43300 and ATCC 33591 were between 2 and 16 and 4 and 16 μg/mL, respectively, and those of vancomycin (reference) were 1 μg/mL. (ii) The natural (S)-plymuthipyranone B exhibited significantly higher activity than the unnatural (R)-antipode against both AACCs. (iii) The natural (R)-plymuthipyranone B and (R)-undecyl synthetic analogue at the C6 position exhibited the highest activity. The present work is the first investigation of the SAR between chiral R and S forms of this chemical class.

Recognition and Sensing of Chiral Organic Molecules by Chiral Porphyrinoids: A Review

Porphyrinoids are extremely attractive for their electronic, optical, and coordination properties as well as for their versatile substitution at meso/β-positions. All these features allow porphyrinoids to behave as chiroptical hosts for chiral recognition by means of non-covalent interactions towards chiral guests. Over the years, chiral discrimination of chiral molecules such as amino acids, alcohols, amines, hydroxy-carboxylic acids, etc. has aroused the interest of the scientific community. Hence, this review aims to report on the progress to date by illustrating some relevant research regarding the chiral recognition of a multitude of chiral organic guests through several chiral mono- and bis-porphyrins via different spectroscopic techniques.

Enantio-sensitive unidirectional light bending

Structured light, which exhibits nontrivial intensity, phase, and polarization patterns in space, has key applications ranging from imaging and 3D micromanipulation to classical and quantum communication. However, to date, its application to molecular chirality has been limited by the weakness of magnetic interactions. Here we structure light’s local handedness in space to introduce and realize an enantio-sensitive interferometer for efficient chiral recognition without magnetic interactions, which can be seen as an enantio-sensitive version of Young’s double slit experiment. Upon interaction with isotropic chiral media, such chirality-structured light effectively creates chiral emitters of opposite handedness, located at different positions in space. We show that if the distribution of light’s handedness breaks left-right symmetry, the interference of these chiral emitters leads to unidirectional bending of the emitted light, in opposite directions in media of opposite handedness, even if the number of the left-handed and right-handed emitters excited in the medium is exactly the same. Our work introduces the concepts of polarization of chirality and chirality-polarized light, exposes the immense potential of sculpting light’s local chirality, and offers novel opportunities for efficient chiral discrimination, enantio-sensitive optical molecular fingerprinting and imaging on ultrafast time scales.