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Advances in machine learning (ML) and automated experimentation are poised to vastly accelerate research in polymer science. Data representation is a critical aspect for enabling ML integration in research workflows, yet many data models impose significant rigidity making it difficult to accommodate a broad array of experiment and data types found in polymer science. This inflexibility presents a significant barrier for researchers to leverage their historical data in ML development. Here we show that a domain specific language, termed Chemical Markdown Language (CMDL), provides flexible, extensible, and consistent representation of disparate experiment types and polymer structures. CMDL enables seamless use of historical experimental data to fine-tune regression transformer (RT) models for generative molecular design tasks. We demonstrate the utility of this approach through the generation and the experimental validation of catalysts and polymers in the context of ring-opening polymerization-although we provide examples of how CMDL can be more broadly applied to other polymer classes. Critically, we show how the CMDL tuned model preserves key functional groups within the polymer structure, allowing for experimental validation. These results reveal the versatility of CMDL and how it facilitates translation of historical data into meaningful predictive and generative models to produce experimentally actionable output., (© 2023. The Author(s).)

Biofouling on the surface of implanted medical devices and biosensors severely hinders device functionality and drastically shortens device lifetime. Poly(ethylene glycol) and zwitterionic polymers are currently considered "gold-standard" device coatings to reduce biofouling. To discover novel anti-biofouling materials, a combinatorial library of polyacrylamide-based copolymer hydrogels is created, and their ability is screened to prevent fouling from serum and platelet-rich plasma in a high-throughput parallel assay. It is found that certain nonintuitive copolymer compositions exhibit superior anti-biofouling properties over current gold-standard materials, and machine learning is used to identify key molecular features underpinning their performance. For validation, the surfaces of electrochemical biosensors are coated with hydrogels and their anti-biofouling performance in vitro and in vivo in rodent models is evaluated. The copolymer hydrogels preserve device function and enable continuous measurements of a small-molecule drug in vivo better than gold-standard coatings. The novel methodology described enables the discovery of anti-biofouling materials that can extend the lifetime of real-time in vivo sensing devices., (© 2022 Wiley-VCH GmbH.)

We report a study combining computational design and experimental evaluation of polyimides with high glass transition temperatures: T g between 220 °C and 500 °C. The computational approach is based on the recently introduced competitive learning algorithm, supervised self-organizing maps (SUSI), which we recast as an ensemble method, e-SUSI. We use e-SUSI to solve both unsupervised and supervised/semisupervised learning tasks capturing structure-property relationships of high- T g polyimides historically studied at Almaden Research Center. Predictors trained on historical data were applied to the combinatorial library of novel polyimides and informed selection of the candidates for synthesis and characterization. In this manner, three new polyimides were prepared with T g values 281 °C, 282 °C, and 331 °C. The measured values closely agree with the predicted values 273 °C, 311 °C, and 335 °C, respectively. We discuss specific reasons that make the proposed computational design strategy attractive in rapid, deliverable-driven efforts with limited, small-batch data sets.

The architectural features of cellular life and its ecologies at larger scales are built upon foundational networks of reactions between molecules that avoid a collapse to equilibrium. The search for life's origins is, in some respects, a search for biotic network attributes in abiotic chemical systems. Radiation chemistry has long been employed to model prebiotic reaction networks, and here we report network-level analyses carried out on a compiled database of radiolysis reactions, acquired by the scientific community over decades of research. The resulting network shows robust connections between abundant geochemical reservoirs and the production of carboxylic acids, amino acids, and ribonucleotide precursors-the chemistry of which is predominantly dependent on radicals. Moreover, the network exhibits the following measurable attributes associated with biological systems: (1) the species connectivity histogram exhibits a heterogeneous (heavy-tailed) distribution, (2) overlapping families of closed-loop cycles, and (3) a hierarchical arrangement of chemical species with a bottom-heavy energy-size spectrum. The latter attribute is implicated with stability and entropy production in complex systems, notably in ecology where it is known as a trophic pyramid. Radiolysis is implicated as a driver of abiotic chemical organization and could provide insights about the complex and perhaps radical-dependent mechanisms associated with life's origins.

Chiral pentose sugars mediate the enantioselective synthesis of amino acid precursors, with the magnitude of the chiral induction dictated by a subtle cooperativity between sugar hydroxyl groups. Ribose and lyxose give opposite chiral preferences, and theoretical calculations reveal the pseudoenantiomeric nature of transition state structures from the two sugars. Prebiotically plausible mixtures of natural d-sugars lead to enantioenrichment of natural l-amino acid precursors. Temporal monitoring and kinetic modeling of the reaction reveal an unusual dynamic kinetic resolution that shifts toward an enantioselective pathway over time, providing an amplification mechanism for the transfer of chiral information. This work adds to growing evidence for synergy in the etiology of the single chirality of the two most important classes of biological molecules, the sugars that make up DNA and RNA and the amino acids that form proteins.

It is generally recognized that a distinguishing feature of life is its peculiar capability to avoid equilibration. The origin of this capability and its evolution along the timeline of abiogenesis is not yet understood. We propose to study an analog of this phenomenon that could emerge in non-biological systems. To this end, we introduce the concept of sustainability of transient kinetic regimes. This concept is illustrated via investigation of cooperative effects in an extended system of compartmentalized chemical oscillators under batch and semi-batch conditions. The computational study of a model system shows robust enhancement of lifetimes of the decaying oscillations which translates into the evolution of the survival function of the transient non-equilibrium regime. This model does not rely on any form of replication. Rather, it explores the role of a structured effective environment as a contributor to the system-bath interactions that define non-equilibrium regimes. We implicate the noise produced by the effective environment of a compartmentalized oscillator as the cause of the lifetime extension.

We consider the hypothesis of the primordial nature of the non-enzymatic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chemical transformations. Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.

Energetics and kinetics of the oxidation of possible soot surface sites by hydroxyl radicals were investigated theoretically. Energetics were calculated by employing density functional theory. Three candidate reactions were selected as suitable prototypes of soot oxidation by OH. The first two, OH + benzene and OH + benzene-phenol complex, did not produce pathways that lead to substantial CO expulsion. The third reaction, OH attack on the phenanthrene radical, had multiple pathways leading to CO elimination. The kinetics of the latter reaction system were determined by solving the master equations with the MultiWell suite of codes. The barrierless reaction rates of this system were computed using the VariFlex program. The computations were carried out over the ranges 1500-2500 K and 0.01-10 atm. At higher temperatures, above 2000 K, the oxidation of phenanthrene radicals by OH followed a chemically activated path. At temperatures lower than 2000 K, chemical activation was not sufficient to drive the reaction to products; reaction progress was impeded by intermediate adducts rapidly de-energizing before reaching products. In such cases, the reaction system was modeled by treating the accumulating adducts as distinct chemical species and computing their kinetics via thermal decomposition. The overall rate coefficient of phenanthrene radical oxidation by OH forming CO was found to be insensitive to pressure and temperature and is approximately 1 × 10(14) cm(3) mol(-1) s(-1). The oxidation of phenanthrene radicals by OH is shown to be controlled by two main processes: H atom migration/elimination and oxyradical decomposition. H atom migration and elimination made possible relatively rapid rearrangement of the aromatic edge to form oxyradicals with favorable decomposition rates. The reaction then continues down the fastest oxyradical pathways, eliminating CO.

The accurate evaluation of molecular properties lies at the core of predictive physical models. Most reliable quantum-chemical calculations are limited to smaller molecular systems while purely empirical approaches are limited in accuracy and reliability. A promising approach is to employ a quantum-mechanical formalism with simplifications and to compensate for the latter with parametrization. We propose a strategy of directly predicting the uncertainty interval for a property of interest, based on training-data uncertainties, which sidesteps the need for an optimum set of parameters.

While structures and reactivities of many small molecules can be computed efficiently and accurately using quantum chemical methods, heuristic approaches remain essential for modeling complex structures and large-scale chemical systems. Here, we present a heuristics-aided quantum chemical methodology applicable to complex chemical reaction networks such as those arising in cell metabolism and prebiotic chemistry. Chemical heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chemical structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chemical methodology to the formose reaction reproduces the experimentally observed reaction products, major reaction pathways, and autocatalytic cycles.

The unique properties of graphene are rooted in its peculiar electronic structure where effects of electron delocalization are pivotal. We show that the traditional view of delocalization as formation of a local or global aromatic bonding framework has to be expanded in this case. A modification of the π-electron system of a finite-size graphene substrate results in a scale-invariant response in the relaxation of interatomic distances and reveals self-organized criticality as a mode of delocalized bonding. Graphene is shown to belong to a diverse class of finite-size extended systems with simple local interactions where complexity emerges spontaneously under very general conditions that can be a critical factor controlling observable properties such as chemical activity, electron transport, and spin-polarization.

Fixed-node diffusion Monte Carlo (FNDMC) is used to simulate the x-ray absorption spectrum of a gas-phase pyrrole molecule at the nitrogen K-edge. Trial wave functions for core-excited states are constructed from ground-state Kohn-Sham determinants substituted with singly occupied natural orbitals from configuration interaction with single excitations calculations of the five lowest valence-excited triplet states. The FNDMC ionization potential (IP) is found to lie within 0.3 eV of the experimental value of 406.1 ± 0.1 eV. The transition energies to anti-bonding virtual orbitals match the experimental spectrum after alignment of IP values and agree with the existing assignments.

The energetics and kinetics of the thermal decomposition of pentacene oxyradicals were studied using a combination of ab initio electronic structure theory and energy-transfer master equation modeling. The rate coefficients of pentacene oxyradical decomposition were computed for the range of 1500-2500 K and 0.01-10 atm and found to be both temperature and pressure dependent. The computational results reveal that oxyradicals with oxygen attached to the inner rings are kinetically more stable than those with oxygen attached to the outer rings. The latter decompose to produce CO at rates comparable to those of phenoxy radical, while CO is unlikely to be produced from oxyradicals with oxygen bonded to the inner rings.

The homolytic O-H bond dissociation energy (BDE) of phenol was determined from diffusion Monte Carlo (DMC) calculations using single determinant trial wave functions. DMC gives an O-H BDE of 87.0 +/- 0.3 kcal/mol when restricted Hartree-Fock orbitals are used and a BDE of 87.5 +/- 0.3 kcal/mol with restricted B3LYP Kohn-Sham orbitals. These results are in good agreement with the extrapolated B3P86 results of Costa Cabral and Canuto (88.3 kcal/mol), the recommended experimental value of Borges dos Santos and Martinho Simões (88.7 +/- 0.5 kcal/mol), and the G3 (88.2 kcal/mol), CBS-APNO (88.2 kcal/mol), CBS-QB3 (87.1 kcal/mol) results of Mulder.

A family of small graphene patches, i.e., rectangular polyaromatic hydrocarbons (PAHs), that have both zigzag and armchair edges is investigated to establish their ground state electronic structure. Broken symmetry density functional theory (DFT) and plane wave DFT were used to characterize the onset of diradical character via relative energies of open-shell and closed-shell singlet states. The perfect pairing (PP) active space approximation of coupled cluster theory was used to characterize diradical character on the basis of promotion of electrons from occupied to unoccupied molecular orbitals. The role of zigzag and armchair edges in the formation of open-shell singlet states is elucidated. In particular, it is found that elongation of the zigzag edge results in an increase of diradical character whereas elongation of the arm chair edge leads to a decrease of diradical character. Analysis of orbitals from PP calculations suggests that diradical states are formally Mobius aromatic multiconfigurational systems.

Patterns of localized and delocalized chemical bonding obtained using the recently proposed adaptive natural density partitioning (AdNDP) provide a qualitative description of electronic structure but miss any quantitative information. Descriptors, such as the electron localization function (ELF), provide quantitative characteristics of bonding and can enhance the usefulness of qualitative patterns. In the present study, we used ELF and a related construct, charge-density-weighted ELF (ELF rho), to characterize localized and delocalized bonding in a variety of systems. It is demonstrated that ELF rho yields a more detailed description than ELF when used to analyze bonding in aromatic, conflicting aromatic, and antiaromatic systems. Both canonical molecular orbitals (CMOs) and localized multicenter two-electron (nc-2e) bonds obtained in the latter case by AdNDP localization are used to calculate ELF rho.

The recently developed adaptive natural density partitioning (AdNDP) method has been applied to a series of golden clusters. The pattern of chemical bonding in Au(20) revealed by AdNDP shows that 20 electrons form a four-center-two-electron (4c-2e) bond in each of 10 tetrahedral cavities of the Au(20) cluster. This chemical bonding picture can readily explain the tetrahedral structure of the Au(20) cluster. Furthermore, we demonstrate that the recovered 4c-2e bonds corresponding to independent structural fragments of the cluster provide important information about chemically relevant fragmentation of Au(20). In fact, some of these bonds can be removed from the initial tetrahedral structure together with the associated atomic fragments, leading to the family of smaller gold clusters. Chemical bonding in the systems formed in such a manner is yet closely related to the bonding in the parental systems showing persistence of the 4c-2e bonding motif. Thus, the multicenter bonds in golden cages recovered by the AdNDP analysis correspond to the fragments that should be seen as building blocks of these chemical systems.

The newly developed adaptive natural density partitioning (AdNDP) method has been applied to a series of organic aromatic mono- and polycyclic molecules, including cyclopropenyl cation, cyclopentadienyl anion, benzene, naphthalene, anthracene, phenanthrene, triphenylene, and coronene. The patterns of chemical bonding obtained by AdNDP are consistent with chemical intuition and lead to unique, compact, graphic formulas. The resulting bonding patterns avoid resonant description and are always consistent with the point symmetry of the molecule. The AdNDP representation of aromatic systems seamlessly incorporates localized and delocalized bonding elements.

A method of description of the chemical bonding combining the compactness and intuitive simplicity of Lewis theory with the flexibility and generality of canonical molecular orbital theory is presented, which is called adaptive natural density partitioning. The objects of chemical bonding in this method are n-center 2-electron bonds, where n goes from one (lone-pair) to the maximum number of atoms in the system (completely delocalized bonding). The algorithm is a generalization of the natural bonding orbital analysis and is based on the diagonalization of the blocks of the first-order density matrix in the basis of natural atomic orbitals. The results obtained by the application of the algorithm to the systems with non-classical bonding can be readily interpreted from the point of view of aromaticity/antiaromaticity concepts. The considered examples include Li4 cluster and a family of planar boron clusters observed in molecular beams.

The structures and bonding of CB6-, C2B5-, and CB62- are investigated by photoelectron spectroscopy and ab initio calculations. It is shown that the global minimum structures for these systems are distorted heptacyclic structures. The previously reported hexacyclic structures with a hypercoordinate central carbon atom are found to be significantly higher in energy and were not populated under current experimental conditions. The reasons why carbon avoids hypercoordination in these planar carbon-boron clusters are explained through detailed chemical-bonding analyses.

The structure and chemical bonding of B16- were studied using ab initio calculations and photoelectron spectroscopy. Its global minimum is found to be a quasi-planar and elongated structure (C2h). Addition of an electron to B16- resulted in a perfectly planar and closed shell B16(2-) (D2h), which is shown to possess 10 pi electrons with a pi-bonding pattern similar to that of naphthalene and can thus be considered as an "all-boron naphthalene", a new member in the growing family of hydrocarbon analogues of boron clusters.

Aromaticity is an important concept in chemistry primarily for organic compounds, but it has been extended to compounds containing transition-metal atoms. Recent findings of aromaticity and antiaromaticity in all-metal clusters have stimulated further research in describing the chemical bonding, structures and stability in transition-metal clusters and compounds on the basis of aromaticity and antiaromaticity, which are reviewed here. The presence of d-orbitals endows much more diverse chemistry, structure and chemical bonding to transition-metal clusters and compounds. One interesting feature is the existence of a new type of aromaticity-delta-aromaticity, in addition to sigma- and pi-aromaticity which are the only possible types for main-group compounds. Another striking characteristic in the chemical bonding of transition-metal systems is the multi-fold nature of aromaticity, antiaromaticity or even conflicting aromaticity. Separate sets of counting rules have been proposed for cyclic transition-metal systems to account for the three types of sigma-, pi- and delta-aromaticity/antiaromaticity. The diverse transition-metal clusters and compounds reviewed here indicate that multiple aromaticity and antiaromaticity may be much more common in chemistry than one would anticipate. It is hoped that the current review will stimulate interest in further understanding the structure and bonding, on the basis of aromaticity and antiaromaticity, of other known or unknown transition-metal systems, such as the active sites of enzymes or other biomolecules which contain transition-metal atoms and clusters.

Novel implementation of the evolutionary approach known as particle swarm optimization (PSO) capable of finding the global minimum of the potential energy surface of atomic assemblies is reported. This is the first time the PSO technique has been used to perform global optimization of minimum structure search for chemical systems. Significant improvements have been introduced to the original PSO algorithm to increase its efficiency and reliability and adapt it to chemical systems. The developed software has successfully found the lowest-energy structures of the LJ(26) Lennard-Jones cluster, anionic silicon hydride Si(2)H(5) (-), and triply hydrated hydroxide ion OH(-) (H(2)O)(3). It requires relatively small population sizes and demonstrates fast convergence. Efficiency of PSO has been compared with simulated annealing, and the gradient embedded genetic algorithm.

During experiment on Au-B alloy clusters, an auro-boron oxide cluster Au2BO- was observed to be an intense peak dominating the Au-B mass spectra, along with weaker signals for AuBO- and Au3BO-. Well-resolved photoelectron spectra have been obtained for the three new oxide clusters, which exhibit an odd-even effect in electron affinities. Au2BO- is shown to be a closed shell molecule with a very high electron detachment energy, whereas AuBO and Au3BO neutrals are shown to be closed shell species with large HOMO-LUMO gaps, resulting in relatively low electron affinities. Density functional calculations were performed for both AunBO- (n = 1-3) and the corresponding HnBO- species to evaluate the analogy between bonding of gold and hydrogen in these clusters. The combination of experiment and theory allowed us to establish the structures and chemical bonding of these tertiary clusters. We find that the first gold atom does mimic hydrogen and interacts with the BO unit to produce a linear AuBO structure. This unit preserves its identity when interacting with additional gold atoms: a linear Au-[AuBO] complex is formed when adding one extra Au atom and two isomeric Au2-[AuBO] complexes are formed when adding two extra Au atoms. Since BO- is isoelectronic to CO, the AunBO- species can be alternatively viewed as Aun interacting with a BO- unit. The structures and chemical bonding in AunBO- are compared to those in the corresponding AunCO complexes.

We present a comprehensive analysis of chemical bonding in pure boron clusters. It is now established in joint experimental and theoretical studies that pure boron clusters are planar or quasi-planar at least up to twenty atoms. Their planarity or quasi-planarity was usually discussed in terms of pi-delocalization or pi-aromaticity. In the current article, we demonstrated that one cannot ignore sigma-electrons and that the presence of two-center two-electron (2c--2e) peripheral B--B bonds together with the globally delocalized sigma-electrons must be taken into consideration when the shape of pure boron cluster is discussed. The global aromaticity (or global antiaromaticity) can be assigned on the basis of the 4n+2 (or 4n) electron counting rule for either pi- or sigma-electrons in the planar structures. We showed that pure boron clusters could have double (sigma- and pi-) aromaticity (B3-, B4, B5+, B6(2+), B7+, B7-, B8, B(8)2-, B9-, B10, B11+, B12, and B13+), double (sigma- and pi-) antiaromaticity (B6(2-), B15), or conflicting aromaticity (B5-,sigma-antiaromatic and pi-aromatic and B14, sigma-aromatic and pi-antiaromatic). Appropriate geometric fit is also an essential factor, which determines the shape of the most stable structures. In all the boron clusters considered here, the peripheral atoms form planar cycles. Peripheral 2c--2e B--B bonds are built up from s to p hybrid atomic orbitals and this enforces the planarity of the cycle. If the given number of central atoms (1, 2, 3, or 4) can perfectly fit the central cavity then the overall structure is planar. Otherwise, central atoms come out of the plane of the cycle and the overall structure is quasi-planar., (Copyright (c) 2006 Wiley Periodicals, Inc.)

Using density functional theory calculations, here we show that a series of B(x)Au(x)2- (x = 5-12) dianions possesses structure and bonding similar to the famous deltahedral closo-borane cages, B(x)H(x)2-. Effective atomic charges on Au in B(x)Au(x)2- are very similar to those on H in B(x)H(x)2-, indicating that Au in the closo-auroboranes is indeed analogous to H in the closo-boranes. The present theoretical predictions of B(x)Au(x)2- suggest that the closo-auroborane species are viable new chemical building blocks that may be synthesized in bulk. The Au atoms in the closo-auroboranes represent highly atomically dispersed Au and may potentially exhibit novel catalytic and chemical properties.

Stannaspherene. The Sn122- cluster is discovered to be a highly stable and highly symmetric icosahedral cage bonded by four delocalized radial pi bonds and nine delocalized on-sphere sigma bonds from the 5p orbitals of the Sn atoms. It has a diameter of 6.1 A, with a large empty interior volume, and can host most transition metal atoms inside, giving rise to a large class of endohedral chemical building blocks for cluster-assembled nanomaterials.

We created mixed triatomic clusters, AlCGe(-), AlSi(2)(-), and AlGe(2)(-), and studied their electronic structure and chemical bonding using photoelectron spectroscopy and ab initio calculations. Excellent agreement between theoretical and experimental photoelectron spectra confirmed the predicted global minimum structures for these species. Chemical bonding analysis revealed that the AlSi(2)(-) and AlGe(2)(-) anions can be described as species with conflicting (sigma-antiaromatic and pi-aromatic) aromaticity. The AlCGe(-) anion represents an interesting example of chemical species which is between classical and aromatic.

Photoelectron spectroscopy was combined with ab initio calculations to elucidate the structure and bonding in Si6 2- and NaSi6 -. Well-resolved electronic transitions were observed in the photoelectron spectra of Si6 - and NaSi6 - at three photon energies (355, 266, and 193 nm). The spectra of NaSi6 - were observed to be similar to those of Si6 - except that the electron binding energies of the former are lower, suggesting that the Si6 motif in NaSi6 - is structurally and electronically similar to that in Si6 -. The electron affinities of Si6 and NaSi6 were measured fairly accurately to be 2.23+/-0.03 eV and 1.80+/-0.05 eV, respectively. Global minimum structure searches for Si6 2- and NaSi6 - were performed using gradient embedded genetic algorithm followed by B3LYP, MP2, and CCSDT calculations. Vertical electron detachment energies were calculated for the lowest Si6 - and NaSi6 - structures at the CCSD(T)/6-311+G(2df), ROVGF/6-311+G(2df), UOVGF/6-311+G(2d), and time-dependent B3LYP/6-311+G(2df) levels of theory. Experimental vertical detachment energies were used to verify the global minimum structure for NaSi6 -. Though the octahedral Si6 2-, analogous to the closo form of borane B6H6 2-, is the most stable form for the bare hexasilicon dianion, it is not the kernel for the NaSi6 - global minimum. The most stable isomer of NaSi6 - is based on a Si6 2- motif, which is distorted into C2v symmetry similar to the ground state structure of Si6 -. The octahedral Si6 2- coordinated by a Na+ is a low-lying isomer and was also observed experimentally. The chemical bonding in Si6 2- and NaSi6 - was understood using natural bond orbital, molecular orbital, and electron localization function analyses.

Photoelectron spectroscopy and ab initio calculations are used to investigate the electronic structure and chemical bonding of Si5(-) and Si5(2-) in NaSi5(-). Photoelectron spectra of Si5(-) and NaSi5(-) are obtained at several photon energies and are compared with theoretical calculations at four different levels of theory, TD-B3LYP, R(U)OVGF, UCCSD(T), and EOM-CCSD(T), all with 6-311+G(2df) basis sets. Excellent agreement is observed between experiment and theory, confirming the obtained ground-state structures for Si5(-) and Si5(2-), which are both found to be trigonal bipyramid with D3h symmetry at several levels of theory. Chemical bonding in Si5, Si5(-), and Si5(2-) is analyzed using NPA, molecular orbitals, ELF, and NICS indices. The bonding in Si5(2-) is compared with that in the isoelectronic and isostructural B5H5(2-) species, but they are found to differ due to the involvement of electron densities, which are supposed to be lone pairs in the skeletal bonding in Si5(2-).

In three recent publications it was predicted that an Al(4)C molecule is planar on the basis of nonhybrid density functional calculations. These conclusions contradict our earlier predictions that Al(4)C is tetrahedral. In order to resolve the controversy we probed in this paper a potential energy surface of Al(4)C using a large variety of theoretical methods including multiconfigurational methods and a variety of one-electron basis sets. We confirmed that the nonhybrid Becke's exchange with Perdew-Wang 1991 correlation functional density functional method predicts that Al(4)C has a planar structure in agreement with the reports of the other three groups. However, in this paper we have shown that high level ab initio calculations at the coupled cluster with singles, doubles, and noniterative triples and at the complete active space self-consistent field followed by multireference configurational interaction levels of theory confirm our earlier prediction that Al(4)C is indeed tetrahedral. The failure of nonhybrid density functional methods to correctly characterize the global minimum structure of Al(4)C demonstrates that it is dangerous to rely solely on these density functional methods in characterization of new molecules and clusters, where experimental structure is not known.