We provide a general thermodynamic framework for the understanding of guest-induced structural transitions in hybrid organic-inorganic materials. The method is based on the analysis of experimental adsorption isotherms. It allows the determination of the free energy differences between host structures involved in guest-induced transitions, especially hard to obtain experimentally. We discuss the general case of adsorption in flexible materials and show how a few key quantities, such as pore volumes and adsorption affinities, entirely determine the phenomenology of adsorption, including the occurrence of structural transitions. On the basis of adsorption thermodynamics, we then propose a taxonomy of guest-induced structural phase transitions and the corresponding isotherms. In particular, we derive generic conditions for observing a double structural transition upon adsorption, often resulting in a two-step isotherm. Finally, we show the wide applicability and the robustness of the model through three case studies of topical hybrid organic-inorganic frameworks: the hysteretic hydrogen adsorption in Co(1,4-benzenedipyrazolate), the guest-dependent gate-opening in Cu(4,4'-bipyridine)(2,5-dihydroxybenzoate)2 and the CO2-induced "breathing" of hybrid material MIL-53.

Thermodynamics of Guest-Induced Structural Transitions in Hybrid Organic-Inorganic Frameworks

The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.

Compositions comprising alternating 2'-modified nucleosides for use in gene modulation

Although carbon dioxide (CO2) is highly abundant, its low reactivity has limited its use in chemical synthesis. In particular, methods for carbon-carbon bond formation generally rely on two-electron mechanisms for CO2 activation and require highly activated reaction partners. Alternatively, radical pathways accessed via photoredox catalysis could provide new reactivity under milder conditions. Here we demonstrate the direct coupling of CO2 and amines via the single-electron reduction of CO2 for the photoredox-catalysed continuous flow synthesis of α-amino acids. By leveraging the advantages of utilizing gases and photochemistry in flow, a commercially available organic photoredox catalyst effects the selective α-carboxylation of amines that bear various functional groups and heterocycles. The preliminary mechanistic studies support CO2 activation and carbon-carbon bond formation via single-electron pathways, and we expect that this strategy will inspire new perspectives on using this feedstock chemical in organic synthesis.

Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow

The carboxylation of sp3-hybridized C-H bonds with CO2 is a challenging transformation. Herein, we report a visible-light-mediated carboxylation of benzylic C-H bonds with CO2 into 2-arylpropionic acids under metal-free conditions. Photo-oxidized triisopropylsilanethiol was used as the hydrogen atom transfer catalyst to afford a benzylic radical that accepts an electron from the reduced form of 2,3,4,6-tetra(9H-carbazol-9-yl)-5-(1-phenylethyl)benzonitrile generated in situ. The resulting benzylic carbanion reacts with CO2 to generate the corresponding carboxylic acid after protonation. The reaction proceeded without the addition of any sacrificial electron donor, electron acceptor or stoichiometric additives. Moderate to good yields of the desired products were obtained in a broad substrate scope. Several drugs were successfully synthesized using the novel strategy.

Photocarboxylation of Benzylic C-H Bonds.

"We'll never be able to know" is a truism that leads to resignation with respect to any experimental effort to search for the chemistry of life's origin. But such resignation runs radically counter to the challenge imposed upon chemistry as a natural science. Notwithstanding the prognosis according to which the shortest path to understanding the metamorphosis of the chemical into the biological is by way of experimental modeling of "artificial chemical life", the scientific search for the route nature adopted in creating the life we know will arguably never truly end. It is, after all, part of the search for our own origin.

Etiology of Potentially Primordial Biomolecular Structures: From Vitamin B12 to the Nucleic Acids and an Inquiry Into the Chemistry of Life's Origin: A Retrospective

XNA (xylo Nucleic Acid): A Summary and New Derivatives

Xylo-Configured oligonucleotides (XNA, xylo nucleic acid): synthesis of conformationally restricted derivatives and hybridization towards DNA and RNA complements

Carbon dioxide is an intrinsically stable molecule. Therefore, its activation requires extra energy input in the form of reactive reagents and/or activated catalysts and, often, harsh reaction conditions. Reported here is a direct carboxylation reaction of aromatic aldehydes with carbon dioxide to afford α-keto acids as added-value products. In situ generation of a reactive cyanohydrin was the key to the successful carboxylation reaction under operationally mild reaction conditions (25-40 °C, 1 atm CO2 ). The resulting α-keto acids served as a platform for α-amino acid synthesis by reductive amination reactions, illustrating the chemical synthesis of essential bioactive molecules from carbon dioxide.

Umpolung Reactivity of Aldehydes toward Carbon Dioxide.

Thermodynamic and kinetic control of a chemical process is the key to access desired products and states. Changes are made when a desired product is not accessible; one may manipulate the reaction with additional reagents, catalysts and/or protecting groups. Here we report the use of carbon dioxide to accelerate cyanohydrin synthesis under neutral conditions with an insoluble cyanide source (KCN) without generating toxic HCN. Under inert atmosphere, the reaction is essentially not operative due to the unfavored equilibrium. The utility of CO2 -mediated selective cyanohydrin synthesis was further showcased by broadening Kiliani-Fischer synthesis under neutral conditions. This protocol offers an easy access to a variety of polyols, cyanohydrins, linear alkylnitriles, by simply starting from alkyl- and arylaldehydes, KCN and an atmospheric pressure of CO2 .

CO2‐Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**

Carbon dioxide is arguably one of the most stable carbon-based molecules, yet enzymatic carbon fixation processes enabled the sustainable life cycle on Earth. Chemical reactions involving CO2-functionalization often suffer from low efficiency with highly reactive substrates. We recently reported mild carboxylation of aldehydes to furnish α-keto acids – a building block for chiral α-amino acids via reductive amination. Here, we discuss potential reaction mechanisms of aldehyde carboxylation reactions based on two promoters: NHCs and KCN in the carboxylation reaction. New DFT mechanistic studies suggested a lower reaction barrier for a CO2-functionalization step, implying a potential role of CO2 in prebiotic evolution of organic molecules in the primordial soup. 1 	Introduction: Aldehydes, Benzoins, Carboxylic Acids 2 	CO2-Activation: NHC, Cyanide, Lewis Acid and Water 3 	A Breslow Intermediate: Benzoin Reaction vs. Carboxylation with CO2
 4 	Carboxylation in the Primordial Soup 5 	Conclusion

Martin Juhl

Papers

XNA (xylo Nucleic Acid): A Summary and New Derivatives

Xylo-Configured oligonucleotides (XNA, xylo nucleic acid): synthesis of conformationally restricted derivatives and hybridization towards DNA and RNA complements

Umpolung Reactivity of Aldehydes toward Carbon Dioxide.

CO2‐Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**

Aldehyde Carboxylation: A Concise DFT Mechanistic Study and a Hypothetical Role of CO2 in the Origin of Life