Guest Back-Folding: A Molecular Design Strategy That Produces a Deep-Red Fluorescent Host/Guest Pair with Picomolar Affinity in Water

One of the major goals of modern supramolecular chemistry, with important practical relevance in many technical fields, is the development of synthetic host/guest partners with ultrahigh affinity and selectivity in water. Currently, most association pairs exhibit micromolar affinity or weaker, and there are very few host/guest systems with <i>K</i>_a > 10⁹ M^–1, apparently due to a barrier imposed by enthalpy/entropy compensation. This present study investigated the threading of a water-soluble tetralactam cyclophane by a deep-red fluorescent squaraine guest with flanking polyethylene glycol chains, an association process that is dominated by a highly favorable enthalpic driving force. A squaraine structure was rationally designed to permit guest back-folding as a strategy to greatly expand the hydrophobic surface area that could be buried upon complexation. Guided by computational modeling, an increasing number of <i>N</i>-benzyl groups were appended to the squaraine core, so that, after threading, the aromatic rings could fold back and stack against the cyclophane periphery. The final design iteration exhibited an impressive combination of fluorescence and supramolecular properties, including ratiometric change in deep-red emission, picomolar affinity (<i>K</i>_a = 5.1 × 10¹⁰ M^–1), and very rapid threading (<i>k</i>_on = 7.9 × 10⁷ M^–1 s^–1) in water at 25 °C. Similar excellent behavior was observed in serum solution. A tangible outcome of this study is a new cyclophane/squaraine association pair that will be a versatile platform for many different types of fluorescence-based imaging and diagnostics applications. From a broader perspective, guest back-folding of aromatic groups is a promising new supramolecular stabilization strategy to overcome enthalpy/entropy compensation and produce ultrahigh affinity [2]­pseudorotaxane complexes in water and biological media

Guest Back-Folding: A Molecular Design Strategy That Produces a Deep-Red Fluorescent Host/Guest Pair with Picomolar Affinity in Water

One of the major goals of modern supramolecular chemistry, with important practical relevance in many technical fields, is the development of synthetic host/guest partners with ultrahigh affinity and selectivity in water. Currently, most association pairs exhibit micromolar affinity or weaker, and there are very few host/guest systems with <i>K</i>_a > 10⁹ M^–1, apparently due to a barrier imposed by enthalpy/entropy compensation. This present study investigated the threading of a water-soluble tetralactam cyclophane by a deep-red fluorescent squaraine guest with flanking polyethylene glycol chains, an association process that is dominated by a highly favorable enthalpic driving force. A squaraine structure was rationally designed to permit guest back-folding as a strategy to greatly expand the hydrophobic surface area that could be buried upon complexation. Guided by computational modeling, an increasing number of <i>N</i>-benzyl groups were appended to the squaraine core, so that, after threading, the aromatic rings could fold back and stack against the cyclophane periphery. The final design iteration exhibited an impressive combination of fluorescence and supramolecular properties, including ratiometric change in deep-red emission, picomolar affinity (<i>K</i>_a = 5.1 × 10¹⁰ M^–1), and very rapid threading (<i>k</i>_on = 7.9 × 10⁷ M^–1 s^–1) in water at 25 °C. Similar excellent behavior was observed in serum solution. A tangible outcome of this study is a new cyclophane/squaraine association pair that will be a versatile platform for many different types of fluorescence-based imaging and diagnostics applications. From a broader perspective, guest back-folding of aromatic groups is a promising new supramolecular stabilization strategy to overcome enthalpy/entropy compensation and produce ultrahigh affinity [2]­pseudorotaxane complexes in water and biological media

Guest Back-Folding: A Molecular Design Strategy That Produces a Deep-Red Fluorescent Host/Guest Pair with Picomolar Affinity in Water

One of the major goals of modern supramolecular chemistry, with important practical relevance in many technical fields, is the development of synthetic host/guest partners with ultrahigh affinity and selectivity in water. Currently, most association pairs exhibit micromolar affinity or weaker, and there are very few host/guest systems with <i>K</i>_a > 10⁹ M^–1, apparently due to a barrier imposed by enthalpy/entropy compensation. This present study investigated the threading of a water-soluble tetralactam cyclophane by a deep-red fluorescent squaraine guest with flanking polyethylene glycol chains, an association process that is dominated by a highly favorable enthalpic driving force. A squaraine structure was rationally designed to permit guest back-folding as a strategy to greatly expand the hydrophobic surface area that could be buried upon complexation. Guided by computational modeling, an increasing number of <i>N</i>-benzyl groups were appended to the squaraine core, so that, after threading, the aromatic rings could fold back and stack against the cyclophane periphery. The final design iteration exhibited an impressive combination of fluorescence and supramolecular properties, including ratiometric change in deep-red emission, picomolar affinity (<i>K</i>_a = 5.1 × 10¹⁰ M^–1), and very rapid threading (<i>k</i>_on = 7.9 × 10⁷ M^–1 s^–1) in water at 25 °C. Similar excellent behavior was observed in serum solution. A tangible outcome of this study is a new cyclophane/squaraine association pair that will be a versatile platform for many different types of fluorescence-based imaging and diagnostics applications. From a broader perspective, guest back-folding of aromatic groups is a promising new supramolecular stabilization strategy to overcome enthalpy/entropy compensation and produce ultrahigh affinity [2]­pseudorotaxane complexes in water and biological media

Guest Back-Folding: A Molecular Design Strategy That Produces a Deep-Red Fluorescent Host/Guest Pair with Picomolar Affinity in Water

One of the major goals of modern supramolecular chemistry, with important practical relevance in many technical fields, is the development of synthetic host/guest partners with ultrahigh affinity and selectivity in water. Currently, most association pairs exhibit micromolar affinity or weaker, and there are very few host/guest systems with <i>K</i>_a > 10⁹ M^–1, apparently due to a barrier imposed by enthalpy/entropy compensation. This present study investigated the threading of a water-soluble tetralactam cyclophane by a deep-red fluorescent squaraine guest with flanking polyethylene glycol chains, an association process that is dominated by a highly favorable enthalpic driving force. A squaraine structure was rationally designed to permit guest back-folding as a strategy to greatly expand the hydrophobic surface area that could be buried upon complexation. Guided by computational modeling, an increasing number of <i>N</i>-benzyl groups were appended to the squaraine core, so that, after threading, the aromatic rings could fold back and stack against the cyclophane periphery. The final design iteration exhibited an impressive combination of fluorescence and supramolecular properties, including ratiometric change in deep-red emission, picomolar affinity (<i>K</i>_a = 5.1 × 10¹⁰ M^–1), and very rapid threading (<i>k</i>_on = 7.9 × 10⁷ M^–1 s^–1) in water at 25 °C. Similar excellent behavior was observed in serum solution. A tangible outcome of this study is a new cyclophane/squaraine association pair that will be a versatile platform for many different types of fluorescence-based imaging and diagnostics applications. From a broader perspective, guest back-folding of aromatic groups is a promising new supramolecular stabilization strategy to overcome enthalpy/entropy compensation and produce ultrahigh affinity [2]­pseudorotaxane complexes in water and biological media

Cyclodextrin Rotaxane with Switchable Pirouetting

A [1]­rotaxane with two threaded α-cyclodextrin (α-CD) wheels was synthesized in 92% yield using a one-pot process at room temperature that employed spontaneous α-CD threading onto a 12-carbon alkyl chain in water followed by an oxime condensation reaction that attached two boronic acid-containing stopper groups. Rapid pirouetting of the threaded α-CD wheels around the encapsulated dumbbell was switched “ON” or “OFF” by the presence of chemical additives that controlled boronate ester bond formation between the interlocked components

Macrocyclic Receptor for Precious Gold, Platinum, or Palladium Coordination Complexes

Two macrocyclic tetralactam receptors are shown to selectively encapsulate anionic, square-planar chloride and bromide coordination complexes of gold­(III), platinum­(II), and palladium­(II). Both receptors have a preorganized structure that is complementary to its precious metal guest. The receptors do not directly ligate the guest metal center but instead provide an array of arene π-electron donors that interact with the electropositive metal and hydrogen-bond donors that interact with the outer electronegative ligands. This unique mode of supramolecular recognition is illustrated by six X-ray crystal structures showing receptor encapsulation of AuCl₄^–, AuBr₄^–, PtCl₄^–2, or Pd₂Cl₆^–2. In organic solution, the 1:1 association constants correlate with specific supramolecular features identified in the solid state. Technical applications using these receptors are envisioned in a wide range of fields that involve precious metals, including mining, recycling, catalysis, nanoscience, and medicine

Macrocyclic Receptor for Precious Gold, Platinum, or Palladium Coordination Complexes

Two macrocyclic tetralactam receptors are shown to selectively encapsulate anionic, square-planar chloride and bromide coordination complexes of gold­(III), platinum­(II), and palladium­(II). Both receptors have a preorganized structure that is complementary to its precious metal guest. The receptors do not directly ligate the guest metal center but instead provide an array of arene π-electron donors that interact with the electropositive metal and hydrogen-bond donors that interact with the outer electronegative ligands. This unique mode of supramolecular recognition is illustrated by six X-ray crystal structures showing receptor encapsulation of AuCl₄^–, AuBr₄^–, PtCl₄^–2, or Pd₂Cl₆^–2. In organic solution, the 1:1 association constants correlate with specific supramolecular features identified in the solid state. Technical applications using these receptors are envisioned in a wide range of fields that involve precious metals, including mining, recycling, catalysis, nanoscience, and medicine

Macrocyclic Receptor for Precious Gold, Platinum, or Palladium Coordination Complexes

Two macrocyclic tetralactam receptors are shown to selectively encapsulate anionic, square-planar chloride and bromide coordination complexes of gold­(III), platinum­(II), and palladium­(II). Both receptors have a preorganized structure that is complementary to its precious metal guest. The receptors do not directly ligate the guest metal center but instead provide an array of arene π-electron donors that interact with the electropositive metal and hydrogen-bond donors that interact with the outer electronegative ligands. This unique mode of supramolecular recognition is illustrated by six X-ray crystal structures showing receptor encapsulation of AuCl₄^–, AuBr₄^–, PtCl₄^–2, or Pd₂Cl₆^–2. In organic solution, the 1:1 association constants correlate with specific supramolecular features identified in the solid state. Technical applications using these receptors are envisioned in a wide range of fields that involve precious metals, including mining, recycling, catalysis, nanoscience, and medicine

Macrocyclic Receptor for Precious Gold, Platinum, or Palladium Coordination Complexes

Two macrocyclic tetralactam receptors are shown to selectively encapsulate anionic, square-planar chloride and bromide coordination complexes of gold­(III), platinum­(II), and palladium­(II). Both receptors have a preorganized structure that is complementary to its precious metal guest. The receptors do not directly ligate the guest metal center but instead provide an array of arene π-electron donors that interact with the electropositive metal and hydrogen-bond donors that interact with the outer electronegative ligands. This unique mode of supramolecular recognition is illustrated by six X-ray crystal structures showing receptor encapsulation of AuCl₄^–, AuBr₄^–, PtCl₄^–2, or Pd₂Cl₆^–2. In organic solution, the 1:1 association constants correlate with specific supramolecular features identified in the solid state. Technical applications using these receptors are envisioned in a wide range of fields that involve precious metals, including mining, recycling, catalysis, nanoscience, and medicine

Macrocyclic Receptor for Precious Gold, Platinum, or Palladium Coordination Complexes

Two macrocyclic tetralactam receptors are shown to selectively encapsulate anionic, square-planar chloride and bromide coordination complexes of gold­(III), platinum­(II), and palladium­(II). Both receptors have a preorganized structure that is complementary to its precious metal guest. The receptors do not directly ligate the guest metal center but instead provide an array of arene π-electron donors that interact with the electropositive metal and hydrogen-bond donors that interact with the outer electronegative ligands. This unique mode of supramolecular recognition is illustrated by six X-ray crystal structures showing receptor encapsulation of AuCl₄^–, AuBr₄^–, PtCl₄^–2, or Pd₂Cl₆^–2. In organic solution, the 1:1 association constants correlate with specific supramolecular features identified in the solid state. Technical applications using these receptors are envisioned in a wide range of fields that involve precious metals, including mining, recycling, catalysis, nanoscience, and medicine