Starburstr̀ dendrimers — Nanoscopic supermolecules according to dendritic rules and principles

Construction of dendritic macromolecules based on the mimicry of macroscopic branching patterns found in trees is reviewed. From this mimicry, synthetic strategies have been developed for the preparation of precise macromolecular building blocks referred to as Starburstr̀/Cascade dendrimers. These dendrimer constructions involve the amplifications of matter (mass) by organizing monomer units around initiator cores according to geometrically driven mathematical rules and principles. The predictable precision of mass and valency (i.e., number of reactive surface groups) displayed by these dendrimers, as a function of generation, validates their proposed role as fundamental nanoscopic building blocks (i.e., particle sizes of 10 −1000Å). This emerging area of “structure-controlled polymers” is defining a fourth new major class of macromolecular architecture. Ideal, defect free structures of Starburst^r̀ polyamidoamine (PAMAM) dendrimers (e.g., NH₃ core; generation = 2.0, MWt. 2,414) have been synthesized in kilogram quantities with overall yields of 60-70%. The precise masses and surface valencies associated with these dendrimer structures allow one to view these entities as “nanoscopic analogues” to atoms. As such, basic rules of chemical combination between dendrimers to give definite, stoichiometric compositions can be defined much as first noted by Dalton for atoms. The use of these nanoscopic building blocks (i.e., 10–1000Å species) to construct supramolecular/supermolecular structures such as nanoscopic compounds, clusters and macro-lattices will be reviewed. Registered trademark of Dendritech Inc.     

A Periodic System of Supramolecular Elements

Chemistry “beyond the molecule” is based on weak, noncovalent, and reversible interactions. As a consequence of these bonds being weak, structural organization by folding and self‐assembly can only be fully exploited with larger molecules that can provide multiple binding sites. Such “supramolecules” can now be synthesized and their folding into desired conformations predicted. A new level of chemistry can now be realized through the creation of non‐natural entities composed of molecular building blocks with defined secondary structures. Herein we define these building blocks as “supramolecular elements”. We anticipate that further research on such large molecules will reveal construction principles dictated by recurring motifs that govern structure formation through folding and self‐assembly. These principles are comparable to the organization of atoms in the Periodic Table of Chemical Elements and may lead to the establishment of a Periodic System of Supramolecular Elements.     

Interfaces between Molecular and Polymeric “Metals”: Electrically Conductive,Structure-Enforced Assemblies of Metallomacrocycles

The design, synthesis, characterization, and understanding of new molecular and macro-molecular substances with “metal-like” electrical properties represents an active research area at the interface of chemistry, physics, and materials science. An important, long-range goal in this field of “materials by design” is to construct supermolecular assemblies which exhibit preordained collective phenomena by virtue of “engineered” interactions between molecular building blocks. In this review, such a class of designed materials is discussed which, in addition, bridges the gap between molecular and polymeric conductors: assemblies of electrically conductive metallomacrocycles. It is seen that efforts to rationally construct stacked metal-like molecular arrays lead logically to structure-enforced macromolecular assemblies of covalently linked molecular subunits. Typical building blocks are robust, chemically versatile metallophthalocyanines. The electrical optical, and magnetic properties of these metallomacrocyclic assemblies and the fragments thereof, provide fundamental information on the connections between local atomic-scale architecture, electronic structure, and the macroscopic collective properties of the bulk solid.     

Ortho‐Stabilized 18F‐Azido Click Agents and their Application in PET Imaging with Single‐Stranded DNA Aptamers

Azido ¹⁸F‐arenes are important and versatile building blocks for the radiolabeling of biomolecules via Huisgen cycloaddition (“click chemistry”) for positron emission tomography (PET). However, routine access to such clickable agents is challenged by inefficient and/or poorly defined multistep radiochemical approaches. A high‐yielding direct radiofluorination for azido ¹⁸F‐arenes was achieved through the development of an ortho‐oxygen‐stabilized iodonium derivative (OID). This OID strategy addresses an unmet need for a reliable azido ¹⁸F‐arene clickable agent for bioconjugation reactions. A ssDNA aptamer was radiolabeled with this agent and visualized in a xenograft mouse model of human colon cancer by PET, which demonstrates that this OID approach is a convenient and highly efficient way of labeling and tracking biomolecules.     

Iminophosphanes: Unconventional Compounds of Main Group Elements

The large number of known stable compounds in which phosphorus has a low coordination number makes it clear that such compounds can no longer be regarded as “exotic” in main group chemistry. While the rich chemistry of P? C multiply bonded systems makes clear their affinity to their organic congeners, iminophosphanes in particular are also of increasing importance. The linkage of a phosphinidine fragment with an imine fragment via a multiple bond gives rise to a class of compounds with an unusually wide range of structural types. This in turn leads to a broad spectrum of chemical behavior which makes iminophosphanes extremely useful synthetic building blocks in organoelement chemistry.     

Recent development in preparation reactivity and biological activity of enaminoketones and enaminothiones and their utilization to prepare heterocyclic compounds

Enaminoketones and esters are gaining increased interest, particularly cyclic‐β‐enaminoesters, which are known as important intermediates for the synthesis of heterocycles and natural products, because the enantioselective preparation of highly functionalized compounds is of central importance in synthetic chemistry. Enaminones are versatile synthetic intermediates that combine the ambident nucleophilicity of enamines with the ambident eletrophilicity of enones. Enaminoketones and enaminonitriles have proven to be versatile building blocks for the synthesis of various heterocycles such as pyridine, pyrimidine and pyrrole deriva tives. Enaminones systems have “enone” character, and may act as acceptors in both 1,2 and 1,4‐additions. In this way the enaminone serves as a scaffold for annulation, and can gain access to systems such as pyrroles indolizidines, quinolizidines and perhydroindoles, all of which are common motifs in alkaloid structures. Enaminones are frequently employed as building blocks for the preparation of a variety of bicyclic compounds of biological interest and have been recently recognized as potential anticonvulsant compounds. Since a large number of developments in the use of enaminones in heterocyclic synthesis have occurred, a review of the recent developments in the synthetic approaches, covering the literature since 1995 until 2004, to these interesting molecules and their useful chemical transformations and biological activity can be considered of considerable value.     

Starburst® dendrimers: A conceptual approach to nanoscopic chemistry and architecture

The nanoscopic domain of structural complexity, which ranges from 1 to 100 run on a particle size scale includes a relatively unexplored area of science which resides between classical chemistry and molecular biology. This rapidly growing area of science is referred to as nanoscopic chemistry and architecture. Concepts evolving in this area lead to a rich variety of precise structures, architecture and properties. These concepts are based on dendritic macromolecules in general and on Starburst® dendrimers in particular. They envision dendrimers as fundamental building blocks which may be used to synthesize nanoscopic compounds, clusters, polymers, etc. Accordingly, dendrimers are regarded architecturally as functional analogues of atoms; therefore, their potential role in nanoscopic chemistry may be compared to that of the atoms in classical chemistry.     

Chemistry of Pentafluorosulfanyl Derivatives and Related Analogs: From Synthesis to Applications

Pentafluorosulfanyl (SF₅)-containing compounds and corresponding analogs are a highly valuable class of fluorine-containing building blocks owing to their unique properties. The reason for that is the set of peculiar and tremendously beneficial characteristics they can impart on molecules once introduced onto them. Despite this, their application in distinct scientific fields remains modest, given the extremely harsh reaction conditions needed to access such compounds. The recent synthetic approaches via S−F, and C−SF₅ bond formation as well as the use of SF₅-containing building blocks embody a “stairway-to-heaven” loophole in the synthesis of otherwise-inaccessible chemical scaffolds only a few years ago. Herein, we report and evaluate the properties of the SF₅ group and analogs, by summarizing synthetic methodologies available to access them as well as following applications in material science and medicinal chemistry since 2015.     

Click Chemistry: Diverse Chemical Function from a Few Good Reactions

Examination of nature's favorite molecules reveals a striking preference for making carbon–heteroatom bonds over carbon–carbon bonds—surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon–heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C−C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C−X−C), an approach we call “click chemistry”. Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect “spring‐loaded” reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.     

New routes in the synthesis of metal oxides,I

Single crystals of numerous new metal oxides “rich in cations” are prepared by using methods such as dis- or conproportionation, thermal decomposition of higher valence oxides, or oxidation of metals and intermetallic compounds (“reactions with the wall”). Exchange reactions allow growth of single crystals even outside of thermodynamic equilibrium. The role of vacancies in structural chemistry as well as in “tailor-made” syntheses is emphasized and illustrated. Molecular aspects of solid state chemistry are demonstrated by cutting chains or rings and by dimerization of small entities. Many examples are provided.     

Fundamentals of Silicon Chemistry: Molecular States of Silicon-Containing Compounds

Silicon and its compounds have made possible the design of new materials, which, from computers to space travel, have helped to shape the technology of our 20th century. Conversely, the demands of new technology have stimulated the fast development of silicon chemistry as part of the “renaissance” of inorganic chemistry. This article uses selected examples of predominantly organosilicon compounds to discuss in simplified terms the measurement and assignment of suitable spectroscopic “molecular fingerprints” as well as the resulting benefit for the preparative chemist. The comparison of “equivalent” states of “chemically related” molecules is emphasized, based on perturbation arguments and supporting quantum-chemical models. Special attention is given to the relation between structure and energy, which allows us to understand and to predict the connectivity between and the spatial arrangement of silicon “building blocks”, the energy-dependent electron distribution over the effective nuclear potentials of a molecular framework, and, especially, the partly considerable effects of “silicon substituents” on molecular properties. Future-directed extensions and applications include polysilane band structures, Rydberg states of chromophores containing silicon centers, redox reactions and ion-pair formation of silicon-substituted π systems, and molecular dynamic phenomena in solution or on thermal fragmentation in the gas phase. The main objective is a set of clear and practical rules for interpreting measurements and planning experiments.     

The Bioinorganic Chemistry of Vanadium

Vanadium is a trace element that plays an important, perhaps essential and general role in the regulation of enzymatic phosphorylations. Several forms of life, including the fly agaric toadstool (Amanita muscaria) and certain sea squirts (ascidians), are able to concentrate vanadium. In other organisms vanadium is part of the active site of some enzymes. Well-studied examples are the nitrogen-fixing bacterium Azotobacter and various seaweeds that use vanadate-dependent peroxidases to synthesize halogenated organic compounds. Despite its importance as a “biometal” both in primitive, prokaryotic organisms (Azotobacter) and in the highly organized ascidians, which represent an early stage in the evolution of vertebrates, the bioinorganic chemistry of vanadium is still in its infancy. Just as young, but undergoing explosive development, is the chemistry of model compounds for vanadium-containing biomolecules, a domain of the bioinorganic coordination chemist, who almost daily discovers compounds with new and surprising structural features. This article reviews this fascinating area of bioinorganic chemistry.     

Liquid-crystalline octopus dendrimers: block molecules with unusual mesophase morphologies

The synthesis and the mesomorphic properties of several new main-chain liquid-crystalline dendrimers, thereafter designated as octopus dendrimers in accordance with their eight sidearms, are reported. In these dendritic systems, the arborescence is ensured by anisotropic segments, acting as branching cells with a double multiplicity, which are incorporated at every node of the dendritic architecture. In such a way, these compounds radically differ from the classical end-functionalized liquid-crystalline dendrimers, the most commonly reported systems. Following our previous report on purely homolithic systems, that is, the building blocks constituting the dendritic matrix are all identical, several heterolithic systems made of different anisotropic blocks have been prepared. The dendritic branches and corresponding dendrimers were synthesized using a modular construction. Polarized optical microscopy and X-ray diffraction studies showed that all of these new octopus dendrimers exhibit either smectic-like or columnar phases with novel morphologies, the nature of the mesophases depending on the number of terminal chains attached to the peripheral groups. The mesomorphism of these heterolithic dendrimers is discussed in terms of their intrinsic architecture and compared to the analogous homolithic octopus systems. Models for the molecular organizations within both the smectic and the columnar phases are proposed on the basis of small Bragg angle X-ray diffraction studies and are supported by molecular modelizations. Moreover, this study showed that the mesophase stability is very sensitive to the nature and to the mutual arrangement (the spatial location) of the mesogenic segments within the dendritic matrix, illustrating the intimate relationships existing between the mesomorphic properties and the molecular architecture of these dendrimers.     

Supramolecular Inorganic Chemistry: Small Guests in Small and Large Hosts

A key reaction in the biological and material world is the controlled linking of simple (molecular) building blocks, a reaction with which one can create mesoscopic structures, which, for example, contain cavities and display specifically desired properties, but also compounds that exhibit typical solid-state structures. The best example in this context is the chemistry of host–guest interactions, which spans the entire range from three- and two-dimensional to one- and “zero-dimensional”, discrete host structures. Members of the class of multidimensional compounds have been classified as such for a long time, for example, clathrates and intercalation compounds. Thus far, however, there are no classifications for discrete inorganic host–guest compounds. The first systematic approach can be applied to novel polyoxometalates, a class of compounds which has only recently become known. Molecular recognition; tailor-made, molecular engineering; control of fragment linkage of spin organization and crystallization; cryptands and coronands as “cages” for cations, anions or anion–cation aggregates as sections of ionic lattices; anions within anions, receptors; host–guest interactions; complementarity, as well as the dialectic terms reduction and emergence are important terms and concepts of supramolecular inorganic chemistry. Of particular importance for future research is the comprehension of the mesoscopic area (molècular assemblies)—that between individual molecules and solids (“substances”)—which acts in the biological world as carrier of function and information and for which interesting material properties are expected. This area is accessible through certain variations of “controlled” self-organization processes, which can be demonstrated by using examples from the chemistry of polyoxometalates. The comprehension of the laws that rule the linking of simple polyhedra to give complex systems enables one to deal with numerous interdisciplinary areas of research: crystal physics and chemistry, heterogeneous catalysis, bioinorganic chemistry (biomineralization), and materials science. In addition, conservative self-organization processes, for example template-directed syntheses, are of importance for natural philosophy in the context of the question about the inherent properties of material systems.     

Synthesis and Applications of Hajos–Parrish Ketone Isomers

Numerous natural products possess ring systems and functionality for which Hajos–Parrish ketone isomers with a transposed methyl group (termed “iso‐Hajos–Parrish ketones”) would be of value. However, such building blocks have not been exploited to the same degree as the more typical Hajos–Parrish hydrindane. An efficient three‐step synthesis of such materials was fueled by a simple method for the rapid preparation of highly functionalized cyclopentenones, several of which are new chemical entities that would be challenging to access through other approaches. Furthermore, one iso‐Hajos–Parrish ketone was converted into two distinct natural product analogues and one natural product. As one indication of the value of these new building blocks, that latter target was obtained in 10 steps, having previously been accessed in 18 steps using the Hajos–Parrish ketone.     

New functionalized, differently fluorinated building-blocks via Michael addition to γ-fluoro-α-nitroalkenes

The Michael addition of ketone-derived enamines, metalated methylene active compounds and N-methyl pyrroles to γ-fluoro-α-nitroalkenes provided in moderate to good isolated yields the corresponding β-fluoroalkyl nitro compounds, which represent new interesting, highly functionalized building blocks in organofluorine chemistry.     

Bright, “Clickable” Porphyrins for the Visualization of Oxygenation under Ambient Light

A new group of “clickable” and brightly emissive metalloporphyrins has been developed for the visualization of oxygenation under ambient light with the naked eye. These alkynyl‐terminated compounds permit the rapid and facile synthesis of oxygen‐sensing dendrimers through azide–alkyne click chemistry. With absorption maxima overlapping with the wavelengths of common commercial laser sources, they are readily applicable to biomedical imaging of tissue oxygenation. An efficient synthetic methodology, featuring the stable trimethylacetyl (pivaloyl) protecting group, is described for their preparation. A paint‐on liquid bandage containing a new, click‐synthesized porphyrin dendrimer has been used to map oxygenation across an ex vivo porcine skin burn model.     

Calixarenes,Macrocycles with (Almost) Unlimited Possibilities

The condensation reaction between p-tert-butylphenol and formaldehyde leads in a single step to good yields of cyclic oligomers in which, depending on the reaction conditions, either four, six, or eight phenol units are joined by methylene bridges. The beakerlike shape of the most stable conformation of the tetramer has led to their being given the name “calixarenes” (calix = chalice). Resorcinol can undergo condensation in a similar manner with a variety of aldehydes to afford cyclic tetramers with the same basic structure (the resorcarenes). In both cases the reaction does not require the use of dilution techniques, so that large quantities of product can be readily obtained. In addition, the parent compounds can be modified in various ways, in particular at the phenolic hydroxy groups or the phenyl residues; these approaches can be used separately or in combination. Calixarenes are thus ideal starting materials for the synthesis of various types of host molecules and can also act as building blocks for the construction of larger molecular systems with defined structures and functions. Their potential applications range from use as highly specific ligands for analytical chemistry, sensor techniques and medical diagnostics to their use in the decontamination of waste water and the construction of artificial enzymes and the synthesis of new materials for non-linear optics or for ultrathin layers and sieve membranes with molecular pores.     

Bioorganometallic Chemistry - Transition Metal Complexes with α-Amino Acids and Peptides

A new, interdisciplinary research area has emerged known as bioorganometallic chemistry. It focuses on the introduction of organometallic fragments into biomolecules (see, for example, structure on the right). “Classical” α-amino acid and peptide ligands have proven particularly versatile, and provide access to compounds that display interesting stereochemistry. α-Amino acids and peptides can be synthesized, labeled, stabilized, or activated by organometallic fragments.     

Supramolecular Dendrimers: Convenient Synthesis by Programmed Self‐Assembly and Tunable Thermoresponsivity

We report here the noncovalent synthesis of thermosensitive dendrimers. Short oligoguanosine strands were linked to the focal point of a dendron by using “click chemistry”, and quadruplex formation was used to drive the self‐assembly process in the presence of metal ions. The dynamic nature of these noncovalent assemblies can be exploited to create combinatorial libraries of dendrimers as demonstrated by the co‐assembly of two components. These supramolecular dendrimers showed thermoresponsive behavior that can be tuned by varying the templating cations or the number of guanines in the oligonucleotide strand.