Knowledge Engineering in Chemistry: From Expert Systems to Agents of Creation.

Passing knowledge from human to human is a natural process that has continued since the beginning of humankind. Over the past few decades, we have witnessed that knowledge is no longer passed only between humans but also from humans to machines. The latter form of knowledge transfer represents a cornerstone in artificial intelligence (AI) and lays the foundation for knowledge engineering (KE). In order to pass knowledge to machines, humans need to structure, formalize, and make knowledge machine-readable. Subsequently, humans also need to develop software that emulates their decision-making process. In order to engineer chemical knowledge, chemists are often required to challenge their understanding of chemistry and thinking processes, which may help improve the structure of chemical knowledge.Knowledge engineering in chemistry dates from the development of expert systems that emulated the thinking process of analytical and organic chemists. Since then, many different expert systems employing rather limited knowledge bases have been developed, solving problems in retrosynthesis, analytical chemistry, chemical risk assessment, etc. However, toward the end of the 20th century, the AI winters slowed down the development of expert systems for chemistry. At the same time, the increasing complexity of chemical research, alongside the limitations of the available computing tools, made it difficult for many chemistry expert systems to keep pace.In the past two decades, the semantic web, the popularization of object-oriented programming, and the increase in computational power have revitalized knowledge engineering. Knowledge formalization through ontologies has become commonplace, triggering the subsequent development of knowledge graphs and cognitive software agents. These tools enable the possibility of interoperability, enabling the representation of more complex systems, inference capabilities, and the synthesis of new knowledge.This Account introduces the history, the core principles of KE, and its applications within the broad realm of chemical research and engineering. In this regard, we first discuss how chemical knowledge is formalized and how a chemist's cognition can be emulated with the help of reasoning algorithms. Following this, we discuss various applications of knowledge graph and agent technology used to solve problems in chemistry related to molecular engineering, chemical mechanisms, multiscale modeling, automation of calculations and experiments, and chemist-machine interactions. These developments are discussed in the context of a universal and dynamic knowledge ecosystem, referred to as The World Avatar (TWA).

Composition-driven archetype dynamics in polyoxovanadates.

Molecular metal oxides often adopt common structural frameworks (i.e. archetypes), many of them boasting impressive structural robustness and stability. However, the ability to adapt and to undergo transformations between different structural archetypes is a desirable material design feature offering applicability in different environments. Using systems thinking approach that integrates synthetic, analytical and computational techniques, we explore the transformations governing the chemistry of polyoxovanadates (POVs) constructed of arsenate and vanadate building units. The water-soluble salt of the low nuclearity polyanion [V6As8O26]4- can be effectively used for the synthesis of the larger spherical (i.e. kegginoidal) mixed-valent [V12As8O40]4- precipitate, while the novel [V10As12O40]8- POVs having tubular cyclic structures are another, well soluble product. Surprisingly, in contrast to the common observation that high-nuclearity polyoxometalate (POM) clusters are fragmented to form smaller moieties in solution, the low nuclearity [V6As8O26]4- anion is in situ transformed into the higher nuclearity cluster anions. The obtained products support a conceptually new model that is outlined in this article and that describes a continuous evolution between spherical and cyclic POV assemblies. This new model represents a milestone on the way to rational and designable POV self-assemblies.

Automated Rational Design of Metal-Organic Polyhedra.

Metal-organic polyhedra (MOPs) are hybrid organic-inorganic nanomolecules, whose rational design depends on harmonious consideration of chemical complementarity and spatial compatibility between two or more types of chemical building units (CBUs). In this work, we apply knowledge engineering technology to automate the derivation of MOP formulations based on existing knowledge. For this purpose we have (i) curated relevant MOP and CBU data; (ii) developed an assembly model concept that embeds rules in the MOP construction; (iii) developed an OntoMOPs ontology that defines MOPs and their key properties; (iv) input agents that populate The World Avatar (TWA) knowledge graph; and (v) input agents that, using information from TWA, derive a list of new constructible MOPs. Our result provides rapid and automated instantiation of MOPs in TWA and unveils the immediate chemical space of known MOPs, thus shedding light on new MOP targets for future investigations.

Metal-metal bonds in polyoxometalate chemistry.

Half a century ago, F. Albert Cotton emphasized the relevance of metal-metal bonding in the constitution of cluster materials. Based on his description, nanoscale polyoxometalates (POMs) normally would not be regarded as cluster materials. One reason is that metal-metal bonding is typically associated with inorganic systems featuring metal centres in low oxidation states, a feature that is not common for POMs. However, over the past decades, there have been increasing reports on POMs integrating different types of metal-metal bonding. This article conceptualises and reviews the area of metal-metal bonded POMs, and their preparation and physicochemical properties. Attention is given to the changes in the electronic structure of POMs, the emergence of covalent dynamics and its impact on the development of applications in catalysis, nanoswitches, donor-acceptor systems, electron storage materials and nanoelectronics (i.e., "POMtronics").

Polyoxoplatinates as covalently dynamic electron sponges and molecular electronics materials.

In organic systems, dynamic covalent chemistry provides an adaptive approach (i.e., "covalent dynamics") where thermodynamic equilibria are used to tailor structural and electronic changes in molecular assemblies. The covalent dynamics finds utility in the design of novel self-healing materials, sensors, and actuators. Herein, using density functional theory (DFT) we explore the structural, electronic and transport properties of the Pt-based polyoxometalate (POM) [PtIII 12O8(SO4)12]4- and its derivatives. The latter POM has six redox responsive {O-Pt-Pt-O} moieties and prospects for storage of up to twelve electrons, thus exemplifying how dynamic covalent chemistry may manifest itself in fully inorganic systems. Simulations of the Au/POM/Au junction show that the electron conduction strongly depends on the redox of the POM but more weakly on its rotations with respect to the Au surface. Moreover, the POM shows promising spin-polarized current behaviour, which can be modulated using bias and gate voltages.

Hybrid polyoxometalates as post-functionalization platforms: from fundamentals to emerging applications.

Polyoxometalates (POMs) represent an important group of metal-oxo nanoclusters, typically comprised of early transition metals in high oxidation states (mainly V, Mo and W). Many plenary POMs exhibit good pH, solvent, thermal and redox stability, which makes them attractive components for the design of covalently integrated hybrid organic-inorganic molecules, herein referred to as hybrid-POMs. Until now, thousands of organic hybrid-POMs have been reported; however, only a small fraction can be further functionalized using other organic molecules or metal cations. This emerging class of 'post-functionalizable' hybrid-POMs constitute a valuable modular platform that permits coupling of POM properties with different organic and metal cation functionalities, thereby expanding the key physicochemical properties that are relevant for application in (photo)catalysis, bioinorganic chemistry and materials science. The post-functionalizable hybrid-POM platforms offer an opportunity to covalently link multi-electron redox responsive POM cores with virtually any (bio)organic molecule or metal cation, generating a wide range of materials with tailored properties. Over the past few years, these materials have been showcased in the preparation of framework materials, functional surfaces, surfactants, homogeneous and heterogeneous catalysts and light harvesting materials, among others. This review article provides an overview on the state of the art in POM post-functionalization and highlights the key design and structural features that permit the discovery of new hybrid-POM platforms. In doing so, we aim to make the subject more comprehensible, both for chemists and for scientists with different materials science backgrounds interested in the applications of hybrid (POM) materials. The review article goes beyond the realms of polyoxometalate chemistry and encompasses emerging research domains such as reticular materials, surfactants, surface functionalization, light harvesting materials, non-linear optics, charge storing materials, and homogeneous acid-base catalysis among others.

Keggin Structure, Quo Vadis?

Working under the supervisor of William Lawrence Bragg at the University of Manchester and being under the direct personal and scientific influence by Linus Pauling, Dr. James Fargher Keggin some 85 years ago published a highly unique discovery-the structure of phosphotungstic acid (Nature 1933, 131, 908-909). This structure sparked the reports of other related polyanions from Keggin's contemporaries, marking the true beginnings of structural polyoxometalate chemistry. In this perspective article, we unveil some aspects and applications of Keggin's structure and discuss how it has shaped the course of our understanding of polyoxometalate chemistry and nanomolecular metal oxides/hydroxides in general.

Superactivity of MOF-808 toward Peptide Bond Hydrolysis.

MOF-808, a Zr(IV)-based metal-organic framework, has been proven to be a very effective heterogeneous catalyst for the hydrolysis of the peptide bond in a wide range of peptides and in hen egg white lysozyme protein. The kinetic experiments with a series of Gly-X dipeptides with varying nature of amino acid side chain have shown that MOF-808 exhibits selectivity depending on the size and chemical nature of the X side chain. Dipeptides with smaller or hydrophilic residues were hydrolyzed faster than those with bulky and hydrophobic residues that lack electron rich functionalities which could engage in favorable intermolecular interactions with the btc linkers. Detailed kinetic studies performed by 1H NMR spectroscopy revealed that the rate of glycylglycine (Gly-Gly) hydrolysis at pD 7.4 and 60 °C was 2.69 × 10-4 s-1 ( t1/2 = 0.72 h), which is more than 4 orders of magnitude faster compared to the uncatalyzed reaction. Importantly, MOF-808 can be recycled several times without significantly compromising the catalytic activity. A detailed quantum-chemical study combined with experimental data allowed to unravel the role of the {Zr6O8} core of MOF-808 in accelerating Gly-Gly hydrolysis. A mechanism for the hydrolysis of Gly-Gly by MOF-808 is proposed in which Gly-Gly binds to two Zr(IV) centers of the {Zr6O8} core via the oxygen atom of the amide group and the N-terminus. The activity of MOF-808 was also demonstrated toward the hydrolysis of hen egg white lysozyme, a protein consisting of 129 amino acids. Selective fragmentation of the protein was observed with 55% yield after 25 h under physiological pH.

Configurational Isomerism in Polyoxovanadates.

A water-soluble derivative of the polyoxovanadate {V15 E6 O42 } (E=semimetal) archetype enables the study of cluster shell rearrangements driven by supramolecular interactions. A reaction unique to E=Sb, induced exclusively by ligand metathesis in peripheral [Ni(ethylenediamine)3 ]2+ counterions, results in the formation of the metastable α1 * configurational isomer of the {V14 Sb8 O42 } cluster type. Contrary to all other polyoxovanadate shell architectures, this isomer comprises an inward-oriented vanadyl group and is ca. 50 and 12 kJ mol-1 higher in energy than the previously isolated α and ß isomers, respectively. We discuss this unexpected reaction in light of supramolecular Sb-O⋅⋅⋅V and Sb-O⋅⋅⋅Sb contacts manifested in {V14 Sb8 O42 }2 dimers detected in the solid state. ESI MS experiments confirm the stability of these dimers also in solution and in the gas phase. DFT calculations indicate that other, as of yet elusive isomers of {V14 Sb8 }, might be accessible as well.

The Cu(i)-catalysed Huisgen 1,3-dipolar cycloaddition route to (bio-)organic functionalisation of polyoxovanadates.

The [V6O13{(OCH2)3CCH2OCH2C[triple bond, length as m-dash]CH}2]2- with two terminal alkyne functionalities exhibits excellent reactivity towards (bio-)organic azides. The designed synthetic protocol for the generation of triazol-modified Lindqvist hexavanadates grants access to bio-"clicked" polyoxometalates with spectroscopically detectable 51V nuclei.

Breaking the Gordian Knot in the Structural Chemistry of Polyoxometalates: Copper(II)-Oxo/Hydroxo Clusters.

This Concept article provides insights into the molecular design and construction aspects of polyoxocuprates (POCus), an emerging class of polyoxometalate (POM)-like architectures featuring low-to-high nuclearity copper(II)-oxo/hydroxo skeletons. POCus have been identified to adopt the structural principles of classical POMs consisting of early transition metals. Their potential to afford motifs of the noble-metal-based POMs is exploited. "Cross-structural topological transformation" is introduced to generalize skeletal relationships between POCus and POMs. The study opens up strategies toward the brand-new structural chemistry of POCus with relevance to homogeneous photocatalysis, medicinal chemistry, molecular magnetism, and quantum computing.

Chiral Dodecanuclear Palladium(II) Thio Cluster: Synthesis, Structure, and Formation Mechanism Explored by ESI-MS and DFT Calculations.

The chiral dodecanuclear palladium(II) thio cluster LaPd12(C3H5NO2S)3(C3H6NO2S)21 (1) was prepared by reacting l-cysteine (l-Cys) with PdCl2 and La2O3 in aqueous solution under carefully controlled conditions. Compound 1 was structurally characterized by single-crystal XRD, TGA, IR, UV-vis, (13)C NMR, and CD spectroscopy. Insight into the dimerization process of 1 was obtained by ESI-MS and DFT calculations.

Rotational Isomerism, Electronic Structures, and Basicity Properties of "Fully-Reduced" V14-type Heteropolyoxovanadates.

We investigated computationally the α-, γ-, and ß-isomeric structures, relative stabilities, and the electronic and basicity properties of magnetic [V(IV)14E8O50](12-) (hereafter referred to as {V14E8}) heteropolyoxovanadates (heteroPOVs) and their heavier chalcogenide-substituted [V(IV)14E8O42X8](12-) ({V14E8X8}) derivatives for E = Si(IV), Ge(IV), and Sn(IV) and X = S, Se, and Te. We used density functional theory (DFT) with scalar relativistic corrections in combination with the conductor-like screening model of solvation. The main purpose of this investigation is to introduce the structure-property relations in heteroPOVs as well as to assist the synthesis and molecular deposition of these molecular vanadium-oxide spin clusters on surfaces. "Fully-reduced" polyoxoanions {V14E8} and {V14E8X8} are virtually comprised of [V(IV)14O38](20-) {V14} skeletons of different symmetries, that is, D2d for α-, D2 for γ-, and D4h for ß-isomers, which are stabilized by the four {E2O3}(2+) and four {E2OX2}(2+) moieties, respectively. Our DFT calculations reveal stability trends α > γ > ß for polyoxoanions {V14E8} and {V14E8X8}, based on relative energies and HOMO-LUMO energy gaps. The α-isomeric polyoxoanions {V14E8} and {V14E8X8} with the high negative net charges may easily pick up protons at the terminal E-Ot and E-Xt sites, respectively, which is evidenced by strongly negative enthalpies of monoprotonation. Energetically favorable sites on polyoxoanions α-{V14E8} and α-{V14E8X8} for electrostatic pairing with countercations were also determined. Among ß and γ isomers, the hitherto unknown γ-[V14Sn8O50](12-) and γ-[V14Sn8O42S8](12-) seem to be the most viable targets for isolation. Furthermore, these Sn-substituted polyoxoanions are of high interest for electrochemical studies because of their capability to act as two-electron redox catalysts.

Platinum-Containing Polyoxometalates: syn- and anti-[Pt(II)2(α-PW11O39)2](10-) and Formation of the Metal-Metal-Bonded di-Pt(III) Derivatives.

The first examples of dimeric, di-Pt(II) -containing heteropolytungstates are reported. The two isomeric di-platinum(II)-containing 22-tungsto-2-phosphates [anti-Pt(II)2(α-PW11O39)2](10-) (1 a) and [syn-Pt(II)2(α-PW11O39)2](10-) (2 a) were synthesized in aqueous pH 3.5 medium using one-pot procedures. Polyanions 1 a and 2 a contain a core comprising two face-on PtO4 units, with a Pt⋅⋅⋅Pt distance of 2.9-3 Å. Both polyanions were investigated by single-crystal XRD, IR, TGA, UV/Vis, (31) P NMR, ESI-MS, CID-MS/MS, electrochemistry, and DFT. On the basis of DFT and electrochemistry, we demonstrated that the {Pt2(II)} moiety in 1 a and 2 a can undergo fully reversible two-electron oxidation to {Pt2(III)}, accompanied by formation of a single Pt-Pt bond. Hence we have discovered the novel subclass of Pt(III)-containing heteropolytungstates.

The polyoxo-22-palladate(ii), [Na2PdO12(As(V)O4)15(As(V)O3OH)](25-) .

The polyoxo-22-palladate [Na2PdO12(As(V)O4)15(As(V)O3OH)](25-) (1), which represents a novel polyoxo-noble-metalate structural type, was synthesized by reaction of Pd(2+) and AsO4(3-) ions in aqueous solution. Polyanion 1 comprises two {NaPd11} units linked by two arsenate bridges, and hence represents the first example of a defect, monolacunary {Pd11} polyoxopalladate nanocube with arsenate capping groups. The title polyanion was characterized in the solid state as well as by theoretical calculations.

The mixed gold-palladium polyoxo-noble-metalate [NaAu(III)4Pd(II)8O8(AsO4)8](11-).

The first fully inorganic, discrete gold-palladium-oxo complex [NaAu(III) 4 Pd(II) 8 O8 (AsO4 )8 ](11-) has been synthesized in aqueous medium. The combination of single-crystal XRD, elemental analysis, mass spectrometry, and DFT calculations allowed establishing the structure and composition of the novel polyanion, and UV/Vis studies suggest that it is stable in neutral aqueous media.