Complexation of p‐Sulfonatocalixarenes with Local Anaesthetics Guests: Binding Structures, Stabilities, and Thermodynamic Origins

Abstract

The binding geometries, abilities and thermodynamic parameters for the intermolecular complexation of three water‐soluble p‐sulfonatocalix[n]arenes (SCnAs), p‐sulfonatocalix[4]arene (SC4A), p‐sulfonatocalix[5]arene (SC5A), andp‐sulfonatothiacalix[4]arene (STC4A), with five local anesthetics (LA), procaine, tetracaine, lidocaine, dibucaine, and procainamide, have been determined by means of 1H NMR spectroscopy, X‐ray crystallography, and isothermal titration calorimetry (ITC). The obtained results show that the complexation of SCnAs with LA guests shows unappreciable guest selectivity, but regular host selectivity: SC4A > SC5A > STC4A for each guest. A large difference in the enthalpy term is responsible for the decrease in the stability constants. The intrinsic relationship between binding structures and host selectivities were comprehensively analyzed and discussed from the viewpoint of thermodynamics. Furthermore, the complexation of SC4A towards LA guests were compared with other macrocyclic hosts, β‐cyclodextrin and cucurbit[7]uril.

The “True” Affinities of Metal Cations to p‐Sulfonatocalix[4]arene: A Thermodynamic Study at Neutral pH Reveals a Pitfall Due to Salt Effects in Microcalorimetry

“…It is gratifying to observe that the large influence of salts and buffers on the complexation of guests by SC4 has recently been increasingly acknowledged. For example, Guo, Liu, and co‐workers long conducted ITC measurements with SC4 in 0.1 M buffer concentration,15, 46, 47 but recently abandoned this routine practice and now use neutralization with base rather than (or in addition to) 0.1 M phosphate buffer to minimize competitive binding by addition of alkali metal ions 47. 60 The importance of avoiding buffers in titration experiments with SC4 was also recently emphasized by Biczók and co‐workers58 and Hof and co‐workers 61…”

“…Despite early NMR spectroscopic indications that alkali metal ions bind with SC4 because they affected the coalescence temperature at high concentrations at pH 8.9 (2.2 m NaCl), [7] it soon become common practice, which persists in part to date, to assess binding constants of guests with SC4 in 0.1 m sodium phosphate buffer solutions. [8][9][10][11][12][13][14][15] Although it was noted that "buffering cannot be used here since CX (SC4) are all capable to interact strongly with many buffers", [16] it was also concluded that "In fact, the (sodium) phosphate buffer (10 mm) has no influence on complexation." [17] Unsurprisingly, in view of this uncertainty, efforts were subsequently made to study the binding of cations by sensitive methods, particularly isothermal titration calorimetry (ITC).…”

Encapsulation of Drug Molecules into Calix[n]arene Nanobaskets. Role of Aminocalix[n]arenes in Biopharmaceutical Field

“…The binding abilities of sodium salts of 123 and 124 with five local anesthetic drugs have been studied by another research group in both, solid state and in solution with revealing of interaction mechanism for each guest–host system (Table ).…”

Density Functional Theory and Atomic Force Microscopy Study of Oleate Functioned on Siderite Surface

“…AFM is practical for measuring the surface properties such as morphology and the mechanical properties of many materials at the nanoscale level [19][20][21], and the technique has become viable to study soft matter especially polymers [22][23][24][25]. Height imaging is a widely used application of AFM in the scientific area, which can be utilized to analyze the morphologies of characterized nano-materials, such as nano-particles [26], nano-tubes [27], and nano-sheets [28].…”