Dendrimers in biomedical applications--reflections on the field.

The modification of metal–organic frameworks (MOFs) in a postsynthetic scheme is discussed in this critical review. In this approach, the MOF is assembled and then modified with chemical reagents with preservation of the lattice structure. Recent findings show amide couplings, isocyanate condensations, ‘click’ chemistry, and other reactions are suitable for postsynthetic modification (PSM). In addition, a number of MOFs, from IRMOF-3 to ZIF-90, are amenable to PSM. The generality of PSM, in both scope of chemical reactions and range of suitable MOFs, clearly indicates that the approach is broadly applicable. Indeed, the rapid increase in reports on PSM demonstrates this methodology will play an increasingly important role in the development of MOFs for the foreseeable future (117 references).

Postsynthetic modification of metal–organic frameworks

Mercury is a widespread pollutant with distinct toxicological profiles, and it exists in a variety of different forms (metallic, ionic, and as part of organic and inorganic salts and complexes). Solvated mercuric ion (Hg), one of the most stable inorganic forms of mercury, is a caustic and carcinogenic material with high cellular toxicity. The most common organic source of mercury, methyl mercury, can accumulate in the human body through the food chain and cause serious and permanent damage to the brain with both acute and chronic toxicity. Methyl mercury is generated by microbial biomethylation in aquatic sediments from water-soluble mercuric ion (Hg). Therefore, routine detection of Hg is central to the environmental monitoring of rivers and larger bodies of water and for evaluating the safety of aquatically derived food supplies. Several methods for the detection of Hg, based upon organic fluorophores or chromophores, semiconductor nanocrystals, cyclic voltammetry, polymeric materials, proteins, and microcantilevers, have been developed. Colorimetric methods, in particular, are extremely attractive because they can be easily read out with the naked eye, in some cases at the point of use. Although there are now several chromophoric colorimetric sensors for Hg, all of them are either limited with respect to sensitivity (current limit of detection 1 mm) and selectivity, kinetically unstable, or incompatible with aqueous environments. Recently, DNA-functionalized gold nanoparticles (DNA– Au NPs) have been used in a variety of forms for the detection of proteins, oligonucleotides, certain metal ions, and other small molecules. DNA–Au NPs have high extinction coefficients (3–5 orders of magnitude higher than those of organic dye molecules) and unique distancedependent optical properties that can be chemically programmed through the use of specific DNA interconnects, which allows one, in certain cases, to detect targets of interest through colorimetric means. Moreover, these structures, when hybridized to complementary particles, exhibit extremely sharp melting transitions, which have been used to enhance the selectivity of detection systems based upon them. By using such an approach, one can typically detect nucleic acid targets in the low nanomolar to high picomolar target concentration range in colorimetric format. The ability to use such particles to detect Hg in the nanomolar concentration range in colorimetric format would be a significant advance, especially when one considers that commercial systems for detecting Hg rely on cumbersome inductively coupled plasma approaches that are not suitable for point-of-use applications. Herein, we present a highly selective and sensitive colorimetric detection method for Hg that relies on thymidine–Hg–thymidine coordination chemistry and complementary DNA–Au NPs with deliberately designed T–T mismatches. When two complementary DNA–Au NPs are combined, they form DNA-linked aggregates that can dissociate reversibly with a concomitant purple-to-red color change. 28] For our novel colorimetric Hg assay, however, we prepared two types of Au NPs (designated as probe A and probe B, see the Supporting Information), each functionalized with different thiolated-DNA sequences (probe A: 5’HS-C10-A10-T-A103’, probe B: 5’HS-C10-T10-T-T103’), which are complementary except for a single thymidine–thymidine mismatch (shown in bold; Scheme 1). Importantly, these particles also form stable aggregates and exhibit the characteristic sharp melting transitions (full width at half maximum< 1 8C) associated with aggregates formed from perfectly complementary particles, but with a lower melting temperature Tm. [17, 18] Since it is known that Hg will coordinate selectively to the bases that make up a T–T mismatch, we hypothesized that Hg would

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/anie.200700269

Colorimetric Detection of Mercuric Ion (Hg2+) in Aqueous Media using DNA-Functionalized Gold Nanoparticles

This review describes a multidimensional treatment of molecular recognition phenomena involving aromatic rings in chemical and biological systems. It summarizes new results reported since the appearance of an earlier review in 2003 in host-guest chemistry, biological affinity assays and biostructural analysis, data base mining in the Cambridge Structural Database (CSD) and the Protein Data Bank (PDB), and advanced computational studies. Topics addressed are arene-arene, perfluoroarene-arene, S⋅⋅⋅aromatic, cation-π, and anion-π interactions, as well as hydrogen bonding to π systems. The generated knowledge benefits, in particular, structure-based hit-to-lead development and lead optimization both in the pharmaceutical and in the crop protection industry. It equally facilitates the development of new advanced materials and supramolecular systems, and should inspire further utilization of interactions with aromatic rings to control the stereochemical outcome of synthetic transformations.

Aromatic rings in chemical and biological recognition: energetics and structures.

Supramolecular chemistry has expanded dramatically in recent years both in terms of potential applications and in its relevance to analogous biological systems. The formation and function of supramolecular complexes occur through a multiplicity of often difficult to differentiate noncovalent forces. The aim of this Review is to describe the crucial interaction mechanisms in context, and thus classify the entire subject. In most cases, organic host-guest complexes have been selected as examples, but biologically relevant problems are also considered. An understanding and quantification of intermolecular interactions is of importance both for the rational planning of new supramolecular systems, including intelligent materials, as well as for developing new biologically active agents.

Binding Mechanisms in Supramolecular Complexes

This paper refines the nature of the interactions between electron-deficient arenes and halide anions. Conclusions are based on (i) new crystal structures containing alkali halide salts with 1,2,4,5-tetracyanobenzene (TCB) and 18-crown-6, (ii) evaluation of crystal structures found in the Cambridge Structural Database, and (iii) MP2/aug-cc-pVDZ calculations of F-, Cl-, and Br- complexes with TCB, 1,3,5-tricyanobenzene, triazine, and hexafluorobenzene. When the halide lies above the plane of the π system, the results establish that three distinctly different types of complexes are possible:  strongly covalent σ complexes, weakly covalent donor−π-acceptor complexes, and noncovalent anion−π complexes. When aryl C−H groups are present, a fourth type of interaction leads to C−H · · · X- hydrogen bonding. Characterization of the different geometries encountered with the four possible binding motifs provides criteria needed to design host architectures containing electron-deficient arenes.

Structural criteria for the design of anion receptors: the interaction of halides with electron-deficient arenes.

The arrangement of urea ligands about different shaped anions has been evaluated with electronic structure calculations. Geometries and binding energies are reported for urea complexes with Cl-, NO3-, and ClO4-. The results yield new insight into the nature of urea−anion interactions and provide structural criteria for the deliberate design of anion selective receptors containing two or more urea donor groups.

Structural design criteria for anion hosts: strategies for achieving anion shape recognition through the complementary placement of urea donor groups.

A coordinatively saturated sulfate encapsulated in a metal–organic framework functionalized with urea hydrogen-bonding groups

Methods for molecular mechanics modeling of coordination compounds

Theoretical calculations,examination of crystallographic data, and experimental binding energies suggest that even in the absence of electron-withdrawing substituents, simple arenes such as benzene form hydrogen bonds with anions that can exceed 50% of the strength of those formed by O−H and N−H groups. Thus, when present in a receptor, even moderately acidic C−H groups can significantly enhance the anion binding affinity and they should be considered as additional binding sites within the host cavity.

Benjamin P. Hay

Papers

Structural criteria for the design of anion receptors: the interaction of halides with electron-deficient arenes.

Structural design criteria for anion hosts: strategies for achieving anion shape recognition through the complementary placement of urea donor groups.

A coordinatively saturated sulfate encapsulated in a metal–organic framework functionalized with urea hydrogen-bonding groups

Methods for molecular mechanics modeling of coordination compounds

Are C-H groups significant hydrogen bonding sites in anion receptors? Benzene complexes with Cl-, NO3-, and ClO4-.