Biomimetic Chemistry Research Articles

From biological analysis to synthetic biology

From biological analysis to synthetic biology

New biomimetic chemistry in water: the anomalous ‘salting-in’ of neutral compounds of natural amino acids with transition metals

The addition of simple salts [such as CaCl 2, MgCl 2 and AgNO 3] greatly enhances the solubility in water of many stable non-electrolytes [M(α) n ] where M is a transition metal ion, α represents the conjugate base of a natural amino acid Hα (operating as a bidentate chelating ligand) and n is the oxidation state of the metal ion. The complex compounds are ‘salted-in’. Both kinetically labile (Cu 2+) and inert (Co 3+, Cr 3+) ions show the effects. Some are due to local changes in the thermodynamic activity of water. The concept of a ‘spectator’ ion is questioned and ‘cybotaxis’ revived. Novel equilibria have been detected in a number of cases [with Cu(α) 2] and several solid adducts are described. The novel adducts trans-[Cu(glyO −) 2]·2AgNO 3 ( 1) and trans, trans-[Cu(glyO −) 2Cl 2][Mg(H 2O) 6]·H 2O ( 2), have been isolated from aqueous silver nitrate and magnesium chloride solutions respectively. Structural features of both are reported and in each case the glycinate ligands coordinate to the copper atoms in a trans arrangement. Structural features of other adducts are briefly reported.

Formation of Porphyrins in the Presence of Acid-Labile Metalloporphyrins: A New Route to Mixed-Metal Multiporphyrin Arrays

The ability to incorporate distinct metalloporphyrins at designated sites in multiporphyrin arrays is essential for diverse applications in materials and biomimetic chemistry. The synthesis of such mixed-metal arrays via acid catalyzed reactions has largely been restricted to metalloporphyrins of stability class II (e.g., Cu, Co, Ni) or I. We describe routes for the rational synthesis of mixed-metal arrays via acid-catalyzed condensations that are compatible with metalloporphyrins of stability class III (e.g., Zn) and IV (e.g., Mg). The routes are demonstrated for p-phenylene-linked arrays. The key finding is that several mild Lewis acids [InCl(3), Sc(OTf)(3), Yb(OTf)(3), and Dy(OTf)(3)], which are known to catalyze the dipyrromethane + dipyrromethane-dicarbinol condensation in CH(2)Cl(2) at room temperature without acidolysis, do not demetalate zinc or magnesium porphyrins under the same conditions. Rational routes to porphyrin dyads and triads employ reaction of a (porphyrin)-dipyrromethane and a (porphyrin)-dipyrromethane-dicarbinol. The porphyrin-forming reactions (six examples) proceed in yields of 18-28%. The metalation states of the arrays prepared in this manner include Zn-free base (ZnFb), MgFb, ZnFbMg, ZnFbZn, and ZnFbFb. Studies of the catalysis process indicate that the dipyrromethane + dipyrromethane-dicarbinol condensation is catalyzed by both the Lewis acid and a Brønsted acid derived in situ from the Lewis acid. Taken together, the ability to employ otherwise "acid-labile" metalloporphyrins as precursors in condensation procedures should broaden the scope of accessible mixed-metal multiporphyrin arrays and motivate further studies of the application of mild Lewis acid catalysts in porphyrin chemistry.

Photoswitchable molecular receptors

The review describes photoswitchable molecular receptors based on crown-ether systems. The important feature of the systems is reversible change in the capacity of a photochromic host molecule for association with guests upon irradiation. From the other side, the exploration of the complex formation process in crown-ether systems leads to a novel approach to the modification of photochromic behavior. The results obtained show that the introduction of crown-ether moieties into dye molecules affords compounds that can change their spectral and photochromic properties upon complex formation. The researchers believe that the novel photochromic systems can now be regarded as being promising for traditional applications (photochromic ophthalmic lenses or camera filters, reversible holographic systems and cosmetics) and molecular electronics, biomimetic chemistry, and optical information storage.

The MrgA Multimeric Complex: a self-assembled nanostructure for inorganic synthesis

AbstractUtilization of protein cages in biomimetic chemistry allows for the deposition of inorganic materials within an organic construct, controlling the size and amount of material deposited within a constrained reaction environment. Previously, protein cages such as viral capsids and ferritins have been used in the constrained synthesis of inorganic materials. The MrgA protein displays a high sequence homology to both bacterial DNA-protecting proteins (Dps) found in many bacterial genera and Ferritin-like proteins (Flp), which have been shown to functionally sequester and store iron in a biologically available form. Here we demonstrate recombinant production, purification and characterization of the MrgA protein and provide evidence that this protein self-assembles to form a multimeric complex. This complex demonstrates characteristics similar to that of ferritin-like proteins such as resistance to iron toxicity, iron incorporation, and resistance to thermal and chemical denaturation. The ability to deposit iron within the putative internal cavity of this protein cage will allow the MrgA complex to be utilized as a spatially constrained reaction vessel for nanomaterial synthesis of other inorganic materials. From a materials science perspective, it will be interesting to see if these organic/inorganic hybrid materials can be harnessed for catalysis, nanomagnetics, and other applications.

Supramolecular Assembly with Calix[6]arene and Copper Ions − Formation of a Novel Tetranuclear Core Exhibiting Unusual Redox Properties and Catecholase Activity

The supramolecular biomimetic chemistry based on calix[6]arene N-ligands has been further explored. A tris(imidazole)CuI complex was treated with 1 mol-equiv. of cuprous ion under dioxygen to produce a tetranuclear cupric species. X-ray structural determination of this novel Cu4 complex revealed that the self-inclusion of an imidazolyl coordinating arm into the hydrophobic calixarene cavity provides the base of coordination for a {ClImCu(OH)2CuIm2}2 assembly. The Cu4 core is maintained in solution and is stable even in a coordinating solvent such as acetonitrile. Magnetic susceptibility measurements evidenced a strong antiferromagnetic coupling in each Cu(OH)2Cu subunit with J = −408 cm−1. The complex displayed catecholase activity in the presence of 3,5-di-tert-butylcatechol behaving as a four-electron hole with, however, a sluggish CuI4 ⇄ CuII4 regeneration through O2 autooxidation. Finally, electrochemical studies revealed two oxidative reversible processes that successively gave rise to a {CuIICuIII}{CuII2} and a {CuIICuIII}2 mixed-valence species that could be characterized by UV/Vis and EPR spectroscopy. The overall structure and behavior of this tetranuclear complex is reminiscent of multicopper enzymes. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

O impacto do crômio nos sistemas biológicos

The impact of biological chromium's activity may be beneficial or not. This review presents the most relevant chemical aspects of these two faces of chromium by covering first, the efforts toward a clearer understanding of the carcinogenic properties of chromium compounds. The biomimetic chemistry of Cr(V) complexes illustrates the interactions of the intermediates formed by Cr(VI) reduction with DNA or oligonucleotides. The importance of trivalent chromium as an essential element is also emphasized by summarizing the recent results of the investigations on trinuclear chromium complexes as models of the cofactor responsible for the insulin activity, as well as good candidates for new nutritional supplements.

Synthesis of meso-substituted chlorins via tetrahydrobilene-a intermediates.

Chlorin building blocks incorporating a geminal dimethyl group in the reduced ring and synthetic handles in specific patterns at the perimeter of the macrocycle are expected to have utility in biomimetic and materials chemistry. A prior route employed condensation of a dihydrodipyrrin (Western half) and a bromodipyrromethane-monocarbinol (Eastern half), followed by oxidative cyclization of the putative dihydrobilene-a to form the meso-substituted zinc chlorin in yields of approximately 10%. The limited stability of the dihydrodipyrrin precluded study of the chlorin-forming process. We now have refined this methodology. A tetrahydrodipyrrin Western half (2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin) has been synthesized and found to be quite stable. The condensation of the Western half and an Eastern half (100 mM each) proceeded smoothly in CH(3)CN containing 100 mM TFA at room temperature for 30 min. The resulting linear tetrapyrrole, a 2,3,4,5-tetrahydrobilene-a, also is quite stable, enabling study of the conversion to chlorin. Refined conditions for the oxidative cyclization were found to include the following: the tetrahydrobilene-a (10 mM), AgTf (3-5 molar equiv), Zn(OAc)(2) (15 molar equiv), and 2,2,6,6-tetramethylpiperidine (15 molar equiv) in CH(3)CN at reflux exposed to air for 4-6 h, affording the zinc chlorin. The chlorin-forming process could be implemented in either a two-flask process or a one-flask process. The two-flask process was applied to form six zinc chlorins bearing substituents such as pentafluorophenyl, 3,5-di-tert-butylphenyl, TMS-ethyl benzoate, iodophenyl, or ethynylphenyl (deprotection of the TMS-ethynyl group occurred during the oxidative cyclization process). The stepwise yields (isolated) for the condensation and oxidative cyclization processes forming the tetrahydrobilene and zinc chlorin were 32-72% and 27-62%, respectively, giving overall yields of zinc chlorin from the Eastern and Western halves of 12-45%. Taken together, the refinements introduced enable 100-mg quantities of chlorin building blocks to be prepared in a facile and rational manner.

ChemInform Abstract: Combinatorial Biomimetic Chemistry: Parallel Synthesis of a Small Library of β‐Hairpin Mimetics Based on Loop III from Human Platelet‐Derived Growth Factor B.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Biomimetic selectivity

Synthetic organic chemistry normally achieves selectivity by manipulation of the intrinsic reactivity of the substrate, but enzyme use is quite a different principle. The geometry of the enzyme-substrate complex determines enzymatic selectivity, completely overwhelming any normal selective reactivities. Biomimetic chemistry aims to imitate the enzymatic style. Some early approaches used attached reagents or templates to direct photochemical and free radical processes, with a combination of geometric and reactivity control. Recent work uses a mimic of the enzyme class cytochrome P-450 to achieve the selective hydroxylations of steroids with complete domination by the geometry of the catalyst-substrate complex. © 2000 John Wiley & Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1:3–11, 2001

Biomimetic selectivity.

Synthetic organic chemistry normally achieves selectivity by manipulation of the intrinsic reactivity of the substrate, but enzyme use is quite a different principle. The geometry of the enzyme-substrate complex determines enzymatic selectivity, completely overwhelming any normal selective reactivities. Biomimetic chemistry aims to imitate the enzymatic style. Some early approaches used attached reagents or templates to direct photochemical and free radical processes, with a combination of geometric and reactivity control. Recent work uses a mimic of the enzyme class cytochrome P-450 to achieve the selective hydroxylations of steroids with complete domination by the geometry of the catalyst-substrate complex.

Combinatorial Biomimetic Chemistry: Parallel Synthesis of a Small Library ofβ-Hairpin Mimetics Based on Loop III from Human Platelet-Derived Growth Factor B

Combinatorial diversity in hypervariable β-hairpin loops is exploited by the immune system to select binding sites on antibodies for a wide variety of different protein antigens. In a first step towards mimicking this strategy in vitro, for the selection of novel protein ligands, an approach is described here for the parallel synthesis of small libraries of conformationally defined β-hairpin protein epitope mimetics. Starting from a protruding hairpin loop in platelet-derived growth factor B (PDGF-B), 8 and 12 residues were first transplanted from the protein to a D-Pro-L-Pro template, to afford the cyclic peptide-loop mimetics 1 and 2, respectively. NMR and MD studies in aqueous solution show that both mimetics populate conformations which closely mimic the β-hairpin in the crystal structure of the native protein (Fig. 5). Based on 1 as a scaffold, a library of 24 mimetics was synthesized in which the four residues at the tip of the loop (VRKK) were held constant, and flanking residues at positions 1, 2, 7, and 8 in the hairpin were varied (Fig. 7). The library was prepared by parallel synthesis in a two-stage solid-phase assembly/solution-phase cyclization process. The products were analyzed by MS, NMR, and CD. 2D-NOESY revealed for most library members characteristic long-range NOEs that show that the hairpin conformation is stably maintained. The results suggest that this approach may be useful for the synthesis of much larger libraries of peptide and protein mimetics based on a β-hairpin scaffold.

Rational synthesis of beta-substituted chlorin building blocks.

Chlorins bearing synthetic handles at specific sites about the perimeter of the macrocycle constitute valuable building blocks. We previously developed methodology for preparing meso-substituted chlorin building blocks and now present methodology for preparing several complementary beta-substituted chlorin building blocks. The chlorins bear one or two beta substituents, one meso substituent, a geminal dimethyl group to lock in the chlorin hydrogenation level, and no flanking meso and beta substituents. The synthesis involves convergent joining of an Eastern half and a Western half. New routes have been developed to two beta-substituted bromo-dipyrromethane monocarbinols (Eastern halves). A new beta-substituted Western half was prepared following the method for preparing an unsubstituted Western half (3,3-dimethyl-2,3-dihydrodipyrrin). Chlorin formation is achieved by a two-flask process of acid-catalyzed condensation followed by metal-mediated oxidative cyclization. beta-Substituted chlorins have been prepared in 18-24% yield bearing a 4-iodophenyl group at the 8-position, a 4-iodophenyl group or a 4-[2-(trimethylsilyl)ethynyl]phenyl group at the 12-position, and a 4-iodophenyl group and a 4-[2-(trimethylsilyl)ethynyl]phenyl group at diametrically opposed beta-positions (2, 12). The latter building block makes possible the stepwise construction of linear multi-chlorin architectures. The chlorins exhibit typical absorption and fluorescence spectra. A systematic shift in the absorption maximum (637-655 nm for the free base chlorins, 606-628 nm for the zinc chlorins) and intensity of the chlorin Q(y)() band (epsilon up to 79 000 M(-)(1) cm(-)(1)) is observed depending on the location of the substituents. The characteristic spectral features and location of substituents in defined positions make these chlorins well suited for a variety of applications in biomimetic and materials chemistry.

Rational Syntheses of Porphyrins Bearing up to Four Different Meso Substituents

Porphyrins bearing specific patterns of substituents are crucial building blocks in biomimetic and materials chemistry. We have developed methodology that avoids statistical reactions, employs minimal chromatography, and affords up to gram quantities of regioisomerically pure porphyrins bearing predesignated patterns of up to four different meso substituents. The methodology is based upon the availability of multigram quantities of dipyrromethanes. A procedure for the diacylation of dipyrromethanes using EtMgBr and an acid chloride has been refined. A new procedure for the preparation of unsymmetrical diacyl dipyrromethanes has been developed that involves (1) monoacylation with EtMgBr and a pyridyl benzothioate followed by (2) introduction of the second acyl unit upon reaction with EtMgBr and an acid chloride. The scope of these acylation methods has been examined by preparing multigram quantities of diacyl dipyrromethanes bearing a variety of substituents. Reduction of the diacyl dipyrromethane to the corresponding dipyrromethane-dicarbinol is achieved with NaBH(4) in methanolic THF. Porphyrin formation involves the acid-catalyzed condensation of a dipyrromethane-dicarbinol and a dipyrromethane followed by oxidation with DDQ. Optimal conditions for the condensation were identified after examining various reaction parameters (solvent, temperature, acid, concentration, time). The conditions identified (2.5 mM reactants in acetonitrile containing 30 mM TFA at room temperature for <7 min) provided reaction without detectable scrambling (LD-MS) for aryl-substituted dipyrromethanes, and trace scrambling for alkyl-substituted dipyrromethanes. The desired porphyrins were obtained in 14-40% yield. The synthesis is compatible with diverse functionalities: amide, aldehyde, carboxylic acid, ester, nitrile, ether, bromo, iodo, ethyne, TMS-ethyne, TIPS-ethyne, perfluoroarene. In total 30 porphyrins of the types A(3)B, trans-A(2)B(2), trans-AB(2)C, cis-A(2)B(2), cis-A(2)BC, and ABCD were prepared, including >1-g quantities of three porphyrins.

Giant Artificial Ion Channels Formed by Self-Assembled, Cationic Rigid-Rod beta-Barrels We thank Dr. E. Buck (Warner Instrument Corp., Hamden, CT) and R. Marclay (University of Geneva) for installation of a BLM workstation, Dr. E. Buck for BLM instructions, A. Pinto, J.-P. Saulnier, the group of Prof. Gülaçar, and Dr. H. Eder for NMR, MS, and elemental analyses, respectively (University of

Future stochastic biomimetic chemistry within toroidal supramolecules will depend on the availability of large, transmembrane, and functionalized internal space of high stability, four properties that characterize the nanopore formed by the hexameric, cationic rigid-rod s-barrel.

Toward a Total Model for the Molybdenum Hydroxylases: Synthesis, Redox, and Biomimetic Chemistry of Oxo-thio-Mo(VI) and -Mo(V) Complexes

Toward a Total Model for the Molybdenum Hydroxylases: Synthesis, Redox, and Biomimetic Chemistry of Oxo-thio-Mo(VI) and -Mo(V) Complexes

Periodic Mesoporous Organosilicas (PMOs): Nanostructured Organic-Inorganic Hybrid Materials

ABSTRACTLateral thinking in biomimetic materials chemistry has permitted chemists to create fascinating structures that mimic the biomaterials optimized by Nature. The integration of organic and inorganic chemistry at multiple length scales gives optimal performance characteristics to biomaterials, such as bone. In a similar fashion, lateral thinking in our lab has enabled us to consolidate the chemistry of inorganic surfactant-templated mesoporous materials with the organic-inorganic hybrid structure of amorphous xerogels. A new class of materials, periodic mesoporous organosilicas (PMOs), has emerged that marries organic and solid-state chemistry in the channels of hexagonally ordered mesoporous materials. Various organic and organometallic groups may be integrated into the framework, creating materials with novel, tunable properties. Surfactant can be solvent-extracted or ion-exchanged to create a high surface area PMO with the framework and the organic group intact. This renders the organic groups accessible for reaction to give a new type of “chemistry of the channels”.

New nanocomposites: putting organic function “inside” the channel walls of periodic mesoporous silica

Nature's accomplishments are inspiring chemists to design new materials based on biologically formed organic and inorganic structures that have been optimized over evolutionary timescales. A recent breakthrough in biomimetic materials chemistry has seen the fusion of organic and inorganic chemistry within the channel walls of periodic mesoporous organosilicas (PMOs). The incorporation of organic moieties in the walls of the liquid crystal templated mesoporous silica confers unique chemical, physical and mechanical properties upon the materials. In this Feature Article, we provide an overview of this new class of materials and propose a classification scheme that will distinguish the PMOs from other mesoporous organic–inorganic hybrid materials.

New Chiral Phosphocontaining Heterocycles on the Basis of Natural Oligohydroxyl Compounds

Principal possibilities of creation of chiral phosphocontaining heterocycles on the basis of natural derivatives of cyclodextrins and dianhydro-D-mannitol are discussed. The obtained compounds possess an internal chiral cavity of a definite size and represent an interest for the solution of modern tasks of biomimetic and supramolecular chemistry.

New Chiral Phosphocontaining Heterocycles on the Basis of Natural Oligohydroxyl Compounds

Principal possibilities of creation of chiral phosphocontaining heterocycles on the basis of natural derivatives of cyclodextrins and dianhydro-D-mannitol are discussed. The obtained compounds possess an internal chiral cavity of a definite size and represent an interest for the solution of modern tasks of biomimetic and supramolecular chemistry.