From molecules to crystal engineering: supramolecular isomerism and polymorphism in network solids.

Inorganic zeolites are used for many practical applications that exploit the microporosity intrinsic to their crystal structures. Organic analogues, which are assembled from modular organic building blocks linked through non-covalent interactions, are of interest for similar applications. These range from catalysis, separation and sensor technology to optoelectronics, with enantioselective separation and catalysis being especially important for the chemical and pharmaceutical industries. The modular construction of these analogues allows flexible and rational design, as both the architecture and chemical functionality of the micropores can, in principle, be precisely controlled. Porous organic solids with large voids and high framework stability have been produced, and investigations into the range of accessible pore functionalities have been initiated. For example, catalytically active organic zeolite analogues are known, as are chiral metal-organic open-framework materials. However, the latter are only available as racemic mixtures, or lack the degree of framework stability or void space that is required for practical applications. Here we report the synthesis of a homochiral metal-organic porous material that allows the enantioselective inclusion of metal complexes in its pores and catalyses a transesterification reaction in an enantioselective manner. Our synthesis strategy, which uses enantiopure metal-organic clusters as secondary building blocks, should be readily applicable to chemically modified cluster components and thus provide access to a wide range of porous organic materials suitable for enantioselective separation and catalysis.

A homochiral metal-organic porous material for enantioselective separation and catalysis

This report describes a number of substructural features which can help to identify compounds that appear as frequent hitters (promiscuous compounds) in many biochemical high throughput screens. The compounds identified by such substructural features are not recognized by filters commonly used to identify reactive compounds. Even though these substructural features were identified using only one assay detection technology, such compounds have been reported to be active from many different assays. In fact, these compounds are increasingly prevalent in the literature as potential starting points for further exploration, whereas they may not be.

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New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays

Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.

Molecular self-assembly and nanochemistry: A chemical strategy for the synthesis of nanostructures

The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing nonclassical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown, and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this Review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore nonclassical platinum(II) complexes with trans geometry or with a monofunctional coordination mode, polynuclea...

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

Thermal dehydration results in the solid-state supramolecular conversion of the helical coordination polymer [{[Cu(sala)]2(H2O)}n] into the chiral three-dimensional covalent open network [{Cu(sala)}n] (shown schematically). X-ray crystallography reveals that hydrogen bonding plays a key role in this process. H2sala=N-(2-hydroxybenzyl)-L-alanine

Thermal Conversion of a Helical Coil into a Three-Dimensional Chiral Framework.

Complexes of CuII, FeIII, CoII, NiII, TiIV and ZnII with 3,5-disubstituted salicylates, and ternary complexes of CuII containing substituted phenanthrolines have been prepared and characterised. The crystal structure of bis(diisopropylsalicylato)(1,10-phenanthroline)copper(II), [Cu(phen)(Hdips)2], has been determined; CuII is in a tetragonal co-ordination environment with in-plane bonds to 2 nitrogens from phen[Cu–N 2.014(4)A] and 2 oxygens from the carboxylates of Hdips [Cu–O 1.951(3)A], with weaker off-axial bonds to carboxylate oxygens [Cu–O 2.557(3)A]. The hydroxyl oxygen of Hdips is not co-ordinated. These complexes have been tested for antiviral and cytotoxic activity. Most are potently cytotoxic, especially [Cu(dmphen)(Hdips)2], where dmphen is 2,9-dimethylphenanthroline.

Cytotoxicity and antiviral activity of transition-metal salicylato complexes and crystal structure of Bis(diisopropylsalicylato)(1,10-phenanthroline)copper(II)

We have studied reactions of the anticancer drug (Pt(NH 3 ) 2 (CBDCA-O,O'] (carboplatin, «Paraplatin», where H 2 CBDCA is cyclobutane-1,1-dicarboxylic acid) with nitrate, phosphate, chloride, and 5'-guanosine monophosphate (5'-GMP) in aqueous solution at 310 K using 1 H, 15 N, ( 1 H, 15 N], and 31 P NMR spectroscopy. A structure for cis-(Pt(NH 3 ) 2 (CBDCA-O)(5'-GMP)] is proposed which accounts for the inequivalence of all six cyclobutane ring protons in this complex.

Ring-opening reactions of the anticancer drug carboplatin : NMR characterization of cis-[Pt(NH3)2(CBDCA-O)(5'-GMP-N7) in solution

Thermal dehydration promotes the topochemical conversion of the hydrogen-bonded dimeric complex [{Zn(sala)(H2 O)2 }2 ]⋅2 H2 O (H2 (sala)=N-(2-hydroxybenzyl)-L-alanine) to generate covalent [{Zn(sala)}n ]. X-ray crystallography reveals that hydrogen bonding plays a key role in this process (see the partial structure on the right).

Topochemical Conversion of a Hydrogen-Bonded Three-Dimensional Network into a Covalently Bonded Framework.

Reactions of the anticancer drug carboplatin ("Paraplatin") with a variety of sulfur-containing amino acids have been investigated by (1)H and (15)N NMR spectroscopy and by HPLC. Thiols react very slowly and sulfur-bridged species containing four-membered Pt(2)S(2) rings are the predominant products. In contrast, reactions with thioether ligands are much more rapid, and kinetics for the initial stages of the reaction with L-methionine have been determined (k = 2.7 x 10(-)(3) M(-)(1) s(-)(1)). Surprisingly, very stable ring-opened species are formed such as cis-[Pt(CBDCA-O)(NH(3))(2)(L-HMet-S)] which has a half-life for Met-S,N ring-closure of 28 h at 310 K. A study of the formation of the analogous product for N-acetyl-L-methionine and its subsequent ring closure is reported. Reactions such as these may play a role in the biological activity of carboplatin.

John D. Ranford

Papers

Thermal Conversion of a Helical Coil into a Three-Dimensional Chiral Framework.

Cytotoxicity and antiviral activity of transition-metal salicylato complexes and crystal structure of Bis(diisopropylsalicylato)(1,10-phenanthroline)copper(II)

Ring-opening reactions of the anticancer drug carboplatin : NMR characterization of cis-[Pt(NH3)2(CBDCA-O)(5'-GMP-N7) in solution

Topochemical Conversion of a Hydrogen-Bonded Three-Dimensional Network into a Covalently Bonded Framework.

Ring-Opened Adducts of the Anticancer Drug Carboplatin with Sulfur Amino Acids.