About Dendrimers: Structure, Physical Properties, and Applications

Diffusion ordered nuclear magnetic resonance spectroscopy: principles and applications

Convergent Dendrons and Dendrimers: from Synthesis to Applications

Intermolecular interactions in solution play an important role in molecular recognition, which lies at the heart of supramolecular and combinatorial chemistry. Diffusion NMR spectroscopy gives information over such interactions and has become the method of choice for simultaneously measuring diffusion coefficients of multicomponent systems. The diffusion coefficient reflects the effective size and shape of a molecular species. Applications of this technique include the estimation of association constants and mapping the intermolecular interactions in multicomponent systems as well as investigating aggregation, ion pairing, encapsulation, and the size and structure of labile systems. Diffusion NMR spectroscopy can also be used to virtually separate mixtures and screen for specific ligands of different receptors, and may assist in finding lead compounds.

Diffusion NMR Spectroscopy in Supramolecular and Combinatorial Chemistry: An Old Parameter—New Insights

http://nathan.instras.com/documentDB/paper-137.pdf

Functional dendrimers, hyperbranched and star polymers

diamide’s behavior on the basis of spectroscopic data should be more straightforward than for 1. Previously reported variabletemperature IH NMR measurements (AG(NH)/A.T) indicated that the intramolecularly hydrogen-bonded and non-hydrogenbonded6 states of 2 are of very similar enthalpy in CD2C12.2a In contrast, when an attempt was made to account for solvation by including three CH2C12 molecules in a “supermolecule” calculation, AM1 predicted the minimum energy intramolecularly hydrogen-bonded conformation of 2 to be 1.9 kcal/mol more enthalpically favorable than the minimum energy non-hydrogen-bonded c~nformat ion .~ In order to provide a more quantitative comparison with the calculations, we have now carried out an IR-based van’t Hoff analysis of the intramolecular hydrogen bonding equilibrium occurring in a 1 mM CH2C12 solution of 2 over the temperature range -69 to 23 OC. Figure 1 shows the N-H stretch region of the IR spectra obtained at high and low temperatures. Both hydrogen-bonded (3340-50 cm-l) and non hydrogen-bonded6 (3443-8 cm-I) bands are observed at each temperature. No hydrogen-bonded N-H stretch band can be detected at any temperature for a 1 mM sample of N-methylcyclohexylactamide (3) in CH,Cl,; therefore, we used this compound to estimate the extinction coefficient of the non-hydrogen-bonded N-H stretch band of 2 as a function of temperature. van’t Hoff analysis (intramolecularly hydrogen-bonded vs non-hydrogen-bonded states; each “state” comprises a set of conformations) indicated that the internally hydrogen-bonded state of 2 is 0.25 f 0.06 kcal/mol less enthalpically favorable and 0.67 f 0.48 eu more entropically favorable than the non-hydrogen-bonded state.’ Since CH2C12 is relatively nonpolar, it is interesting that the internally hydrogen-bonded and non-hydrogen-bonded states of 2 have very similar enthalpies, with the state containing the N-H-O=C interaction slightly less enthalpically favorable. An ideal amide-amide hydrogen bond should be enthalpically superior to any interaction between the amide group and the solvent. The enthalpic similarity of the internally hydrogen-bonded and non-hydrogen-bonded states of 2 may result from at least two factors: (1) the geometry of the seven-membered-ring hydrogen bond is not optimal for the amide-amide interaction (e.g., a nonlinear N-H-0 angle is unavoidable); (2) closure of the hydrogen-bonded ring may involve the development of torsional strain and/or other enthalpically unfavorable interactions. The entropic similarity between the internally hydrogen-bonded and non-hydrogen-bonded states may arise from the fact that these two states enjoy similar degrees of conformational mobility2c and/or from desolvation associated with intramolecular hydrogen bond formation.* (The breadth and asymmetry of the hydrogen-bonded N-H stretch band in Figure 1 is consistent with the existence of multiple hydrogen-bonded ring conformations.) Why does AM1 overestimate the enthalpic favorability of the intramolecularly hydrogen-bonded state of 2? One potential source of error is indicated by the comparison between ab initio and AM1 results for the hydrogen-bonded formamide dimer reported by Novoa and Whangboe3 When interaction energy was examined as a function of the N-H--0 angle, the ab initio calculations predicted that the hydrogen bond energy becomes increasingly unfavorable as the angle decreases below 150°.9 For an N-H-0 angle of 120’ (the smallest angle examined), the ab initio interaction energy was 1.5 kcal/mol less favorable than in the

Diffusion-ordered two-dimensional nuclear magnetic resonance spectroscopy

Diffusion-ordered 2D NMR (DOSY) experiments have been developed for the analysis of mixtures. These experiments yield conventional chemical shift spectra in one dimension and spectra of diffusion coefficients (or approximate molecular radii) in the other. At the heart of this method are the analysis and display of data obtained with pulsed field gradient (PFG) NMR techniques. At each point on the chemical shift axis, a set of intensities is obtained as a function of K 2 (K=γgδ, whore γ is the magnetogyric ratio and g and δ are the gradient pulse amplitude and duration, respectively)

Resolution of discrete and continuous molecular size distributions by means of diffusion-ordered 2D NMR spectroscopy

Three series of cascade polymers possessing identical internal hierarchical architectures, but with either acidic, neutral, or basic terminal functionality, have been prepared. An iterative synthetic strategy war employed that involved amidation (via peptide coupling methods) of carboxylic acids with branched amines possessing the desired protected functionalities, followed by facile deprotection to give water-soluble cascade polymers (dendrimers). Diffusion ordered spectroscopy ( 1 H DOSY NMR) of these cascade polyamides revealed that some of these polymers swell or shrink in response to the stimulus of a pH change

"Smart" Cascade Polymers. Modular Syntheses of Four-Directional Dendritic Macromolecules with Acidic, Neutral, or Basic Terminal Groups and the Effect of pH Changes on Their Hydrodynamic Radii

Cascade polymers. 35. pH dependence of hydrodynamic radii of acid-terminated dendrimers

Diffusion-ordered 2D NMR spectroscopy (DOSY) has been applied to the analysis of aqueous mixtures. Pulsed field gradient NMR (PFG-NMR) experiments were performed with special provisions for minimizing the effects of pulse-induced eddy currents and with sample spinning during the data acquisition period. The FT PFG-NMR data sets were processed with the data inversion program SPLMOD to resolve and identify the solutes on the basis of diffusion coefficients that normally are related to molecular size. Contour plots were then constructed in which conventional 1D NMR spectra were displayed in one dimension and diffusion spectra in the other

Kevin F. Morris

Papers

Diffusion-ordered two-dimensional nuclear magnetic resonance spectroscopy

Resolution of discrete and continuous molecular size distributions by means of diffusion-ordered 2D NMR spectroscopy

"Smart" Cascade Polymers. Modular Syntheses of Four-Directional Dendritic Macromolecules with Acidic, Neutral, or Basic Terminal Groups and the Effect of pH Changes on Their Hydrodynamic Radii

Cascade polymers. 35. pH dependence of hydrodynamic radii of acid-terminated dendrimers

Analysis of mixtures based on molecular size and hydrophobicity by means of diffusion-ordered 2D NMR