Interface Nucleus Complementarity: An Iterative Process for the Discovery of Modular Intermetallics Guided by Chemical Pressure.

We present an iterative process for the discovery of modular intermetallic structures based on a recently developed interface nucleus approach. The process begins with the proposal of a suitable geometric motif that may serve as an interface nucleus. We then screen crystallographic databases for structures containing this motif as potential intergrowth partners. The extent to which pairs of these structures are likely to combine into more complicated assembles is then assessed with a new chemical pressure-based metric, interface nucleus complementarity (INC). Promising combinations of structures are translated into systems for synthesis, with new compounds providing either support for the importance of the original interface nucleus or new geometrical motifs for the next round of analysis. We demonstrate this process using a fragment derived from the σ-phase structure as a starting point, leading to the synthesis of PrMg4.13Zn10.20 and a new motif to seed the next cycle.

A General Synthetic Strategy toward the Truxillate Natural Products via Solid-State Photocycloadditions.

The truxillates constitute a large class of dimeric natural products featuring a central, highly substituted cyclobutane core. In principle, these structures could be efficiently synthesized via [2 + 2] photocycloaddition. However, the difficulty in controlling the high-energy electronically excited reactive intermediates in the solution state can lead to poor regio- and diastereocontrol. This has limited the use of photocycloaddition methodology toward the synthesis of this important class of natural products. Herein, we demonstrate that acid-controlled precipitation of C-acyl imidazoles promotes a highly selective solid-state photocycloaddition, and the products of this reaction can be quickly transformed into truxillate natural products.

Enantioselective Paternò-Büchi Reactions: Strategic Application of a Triplet Rebound Mechanism for Asymmetric Photocatalysis.

The Paternò-Büchi reaction is the [2 + 2] photocycloaddition of a carbonyl with an alkene to afford an oxetane. Enantioselective catalysis of this classical photoreaction, however, has proven to be a long-standing challenge. Many of the best-developed strategies for asymmetric photochemistry are not suitable to address this problem because the interaction of carbonyls with Brønsted or Lewis acidic catalysts can alter the electronic structure of their excited state and divert their reactivity toward alternate photoproducts. We show herein that a triplet rebound strategy enables the stereocontrolled reaction of an excited-state carbonyl compound in its native, unbound state. These studies have resulted in the development of the first highly enantioselective catalytic Paternò-Büchi reaction, catalyzed by a novel hydrogen-bonding chiral Ir photocatalyst.

A Synthetic Strategy toward S-, N-, and O-Heterocyclooctynes Facilitates Bioconjugation Using Multifunctional Handles.

Over the past two decades, the introduction of bioorthogonal reactions has transformed the ways in which chemoselective labeling, isolation, imaging, and drug delivery are carried out in a complex biological milieu. A key feature of a good bioorthogonal probe is the ease with which it can be attached to a target compound through bioconjugation. This paper describes the expansion of the utility of a class of unique S-, N-, and O-containing heterocyclooctynes (SNO-OCTs), which show chemoselective reactivity with type I and type II dipoles and divergent reactivities in response to electronic tuning of the alkyne. Currently, bioconjugation of SNO-OCTs to a desired target is achieved through an inconvenient aryl or amide linker at the sulfamate nitrogen. Herein, a new synthetic approach toward general SNO-OCT scaffolds is demonstrated that enables the installation of functional handles at both propargylic carbons of the heterocycloalkyne. This capability increases the utility of SNO-OCTs as labeling reagents through the design of bifunctional bioorthogonal probes with expanded capabilities. NMR kinetics also revealed up to sixfold improvement in cycloaddition rates of new analogues compared to first-generation SNO-OCTs.

Toward Predicting the Assembly of Modular Intermetallics from Chemical Pressure Analysis: The Interface Nucleus Approach.

Complex intermetallic phases are often constructed from domains derived from simpler structures arranged into hierarchical assemblies. These modular arrangements offer intriguing prospects, such as the integration of the properties of distinct compounds into a single material or for the emergence of new properties from the interactions among different domains. In this article, we develop a strategy for the design of such complex structures, which we term the interface nucleus approach. Within this framework, the assembly of complex structures is facilitated by interface nuclei: geometrical motifs shared by two parent structures that serve as a region of overlap to nucleate or seed the formation of a combined structure. Our central hypothesis is that the formation of an interface between structures at these motifs creates opportunities for the relief of atomic packing stresses, as revealed by Density Functional Theory-Chemical Pressure (DFT-CP) analysis: when corresponding interatomic contacts in two structures exhibit complementarity─negative CP with positive CP or intense CP with mild CP─the intergrowth allows for a more balanced packing arrangement. To illustrate the application of the interface nucleus concept, we analyze three modular intermetallic structures, the σ-phase (FeCr), PuNi3, and Ca6Cu6Al5 types. In each case, the assembly of the structure can be connected to complementary CP features in an interface nucleus shared by its parent structures, while the distribution of the interface nuclei in the parents serves to template the geometry of the overall framework. In this way, the interface nucleus approach points toward avenues for the design of modular intermetallics from the CP schemes of potential partner structures.

Tuning Structure and Excitonic Properties of 2D Ruddlesden-Popper Germanium, Tin, and Lead Iodide Perovskites via Interplay between Cations.

The compositional tunability of 2D metal halide perovskites enables exploration of diverse semiconducting materials with different structural features. However, rationally tuning the 2D perovskite structures to target physical properties for specific applications remains challenging, especially for lead-free perovskites. Here, we study the effect of the interplay of the B-site (Ge, Sn, and Pb), A-site (cesium, methylammonium, and formamidinium), and spacer cations on the structure and optical properties of a new series of 2D Ruddlesden-Popper perovskites using the previously unreported spacer cation 4-bromo-2-fluorobenzylammonium (4Br2FBZ). We report eight new crystal structures and study the consequence of varying the B-site (Pb, Sn, Ge) and dimension (n = 1, 2, vs 3D). Dimension strongly influences local distortion and structural symmetry, and the increased octahedral tilting and lone pair effects in Ge perovskites lead to a polar n = 2 perovskite that exhibits second harmonic generation, (4Br2FBZ)2(Cs)Ge2I7. In contrast, the analogous Sn and Pb perovskites remain centrosymmetric, but the B-site metal influences the photoluminescence properties. The Pb perovskites exhibit broad, defect-mediated emission at low temperature, whereas the Sn perovskites show purely excitonic emission over the entire temperature range, but the carrier recombination dynamics depend on dimensionality and dark excitonic states. Wholistic understanding of these differences that arise based on cations and dimensionality can guide the rational materials design of 2D perovskites for targeting physical properties for optoelectronic applications based on the interplay of cations and the connectivity of the inorganic framework.

Re-Evaluation of Product Outcomes in the Rh-Catalyzed Ring Expansion of Aziridines with N-Sulfonyl-1,2,3-Triazoles.

N-heterocycles are prevalent in pharmaceuticals and natural products, but traditional methods often do not introduce significant stereochemical complexity into the ring. We previously reported a Rh-catalyzed ring expansion of aziridines and N-sulfonyl-1,2,3-triazoles to furnish dehydropiperazines with excellent diastereocontrol. However, later studies employing ketone-containing carbene precursors showed that [3,9]-bicyclic aziridine formation competes with production of the desired heterocyclic scaffolds. In light of these surprising results, our initial findings were re-examined both experimentally and computationally to reveal how noncovalent interactions and restricted bond rotation in the aziridinium ylide intermediate promote this unexpected reaction pathway.

A decarbonylative approach to alkylnickel intermediates and C(sp3)-C(sp3) bond formation.

The myriad nickel-catalyzed cross-coupling reactions rely on the formation of an organonickel intermediate, but limitations in forming monoalkylnickel species have limited options for C(sp3) cross-coupling. The formation of monoalkylnickel(II) species from abundant carboxylic acid esters would be valuable, but carboxylic acid derivatives are primarily decarboxylated to form alkyl radicals that lack the correct reactivity. In this work, we disclose a facile oxidative addition and decarbonylation sequence that forms monoalkylnickel(II) intermediates through a nonradical process. The key ligand, bis(4-methylpyrazole)pyridine, accelerates decarbonylation, stabilizes the alkylnickel(II) intermediate, and destabilizes off-cycle nickel(0) carbonyl species. The utility of this new reactivity in C(sp3)-C(sp3) bond formation is demonstrated in a reaction that is challenging by purely radical methods-the selective cross-coupling of primary carboxylic acid esters with primary alkyl iodides.

Occupational modulation in the (3+1)-dimensional incommensurate structure of (2S,3S)-2-amino-3-hydroxy-3-methyl-4-phenoxybutanoic acid dihydrate.

The incommensurately modulated structure of (2S,3S)-2-amino-3-hydroxy-3-methyl-4-phenoxybutanoic acid dihydrate (C11H15NO4·2H2O or I·2H2O) is described in the (3+1)-dimensional superspace group P212121(0ß0)000 (ß = 0.357). The loss of the three-dimensional periodicity is ascribed to the occupational modulation of one positionally disordered solvent water molecule, where the two positions are related by a small translation [ca 0.666 (9) Å] and ∼168 (5)° rotation about one of its O-H bonds, with an average 0.624 (3):0.376 (3) occupancy ratio. The occupational modulation of this molecule arises due to the competition between the different hydrogen-bonding motifs associated with each position. The structure can be very well refined in the average approximation (all satellite reflections disregarded) in the space group P212121, with the water molecule refined as disordered over two positions in a 0.625 (16):0.375 (16) ratio. The refinement in the commensurate threefold supercell approximation in the space group P1121 is also of high quality, with the six corresponding water molecules exhibiting three different occupancy ratios averaging 0.635:0.365.

A Lead-Free Ferroelectric 2D Dion-Jacobson Tin Iodide Perovskite.

2D hybrid organic-inorganic halide perovskites emerge as a new class of 2D semiconductors with the potential to combine excellent optoelectronic properties with symmetry-enabled properties such as ferroelectricity. Although many lead-based ferroelectric 2D halide perovskites are reported, there is yet to be a conclusive report of ferroelectricity in tin-based 2D perovskites. Here, the structures and properties of a new series of 2D Dion-Jacobson (DJ) Sn perovskites: (4AMP)SnI4, (4AMP)(MA)Sn2I7, and (4AMP)(FA)Sn2I7 (4AMP = 4-(aminomethyl)piperidinium, MA = methylammonium, and FA = formamidinium), are reported. Structural characterization reveals that (4AMP)SnI4 is polar with in-plane spontaneous polarization whereas (4AMP)(MA)Sn2I7 and (4AMP)(FA)Sn2I7 are centrosymmetric. Further, (4AMP)SnI4 displays second harmonic generation (SHG) and polarization-electric field hysteresis measurements confirm it is ferroelectric with a spontaneous polarization of 10.0 µC cm-2 at room temperature. (4AMP)SnI4 transitions into a centrosymmetric structure above 367 K. As the first direct experimental observation of the spontaneous ferroelectric polarization of a Sn-based 2D hybrid perovskite, this work opens up environmentally friendly 2D tin halide perovskites for ferroelectricity and other physical property studies.

Charting the coordinative landscape of the 18F-Sc/44Sc/177Lu triad with the tri-aza-cyclononane (tacn) scaffold.

The widely established PET isotope 18F does not have a therapeutic partner. We have recently established that the Sc-F bond can be formed under aqueous, high yielding conditions, paving the way to providing 18F as diagnostic partners to 47Sc and 177Lu radiotherapeutics. Here, we synthesized a library of tacn-based chelators comprised of 10 structurally unique permutations incorporating acetate, methyl-benzylamide and picolinate donor arms. The chelator library encompasses chelators ranging from 6- to 9-dentate, and produces complex changes ranging from +3 to -1. The corresponding Sc-F/Sc and Lu chelate complexes were characterized using computational, spectroscopic and potentiometric methods, followed by optimization of radiolabeling with 18F, 44Sc and 177Lu and concluded by in vivo validation. We identify characterization benchmarks that chart the coordinative landscape of radiochelation approaches for this unusual triad. Our screening identifies two ligand systems, H2L111 and H3L201 as ideal, readily functionalizable constructs for prospective, targeted theranostic applications with 18F/44Sc/177Lu.

Self-Consistent Chemical Pressure Analysis: Resolving Atomic Packing Effects through the Iterative Partitioning of Space and Energy.

While planewave DFT methods offer capabilities to calculate the relative stabilities and many physical properties exhibited by solid state structures, their detailed numerical output does not easily map onto the often empirical concepts and parameters used by synthetic chemists or materials scientists. The DFT-chemical pressure (CP) method is an approach to bridging this divide by explaining or anticipating a variety of structural phenomena in terms of atomic size and packing effects, but its reliance on adjustable parameters has limited the method's predictive potential. In this article, we present the self-consistent (sc)-DFT-CP analysis, in which the criterion of self-consistency is used to automatically solve these parameterization issues. We begin by illustrating the need for this improved method with the results for a series of CaCu5-type/MgCu2-type intergrowth structures, where unphysical trends emerge that have no clear structural origin. To address these challenges, we derive iterative treatments for assigning ionicity and for the partitioning of the EEwald + Eα terms in the DFT total energy into homogeneous and localized terms. In this method, self-consistency is achieved between the input and output charges from a variation of the Hirshfeld charge scheme, while the partitioning of the EEwald + Eα terms is adjusted to create equilibrium between the net atomic pressures calculated within atomic regions and from the interatomic interactions. The behavior of the sc-DFT-CP method is then tested using electronic structure data for several hundred compounds from the Intermetallic Reactivity Database. Finally, we return to the CaCu5-type/MgCu2-type intergrowth series with the sc-DFT-CP approach, showing that trends in the series are now easily traced to changes in the thicknesses of the CaCu5-type domains and lattice mismatch at the interface. Through this analysis and the complete update to the CP schemes in the IRD, the sc-DFT-CP method is demonstrated as a theoretical tool for the investigation of atomic packing issues across intermetallic chemistry.