A semi-automated quantum-mechanical workflow for the generation of molecular monolayers and aggregates.

Organic electronics (OE) such as organic light-emitting diodes or organic solar cells represent an important and innovative research area to achieve global goals like environmentally friendly energy production. To accelerate OE material discovery, various computational methods are employed. For the initial generation of structures, a molecular cluster approach is employed. Here, we present a semi-automated workflow for the generation of monolayers and aggregates using the GFNn-xTB methods and composite density functional theory (DFT-3c). Furthermore, we present the novel D11A8MERO dye interaction energy benchmark with high-level coupled cluster reference interaction energies for the assessment of efficient quantum chemical and force-field methods. GFN2-xTB performs similar to low-cost DFT, reaching DFT/mGGA accuracy at two orders of magnitude lower computational cost. As an example application, we investigate the influence of the dye aggregate size on the optical and electrical properties and show that at least four molecules in a cluster model are needed for a qualitatively reasonable description.

Efficient calculation of electronic coupling integrals with the dimer projection method via a density matrix tight-binding potential.

Designing organic semiconductors for practical applications in organic solar cells, organic field-effect transistors, and organic light-emitting diodes requires understanding charge transfer mechanisms across different length and time scales. The underlying electron transfer mechanisms can be efficiently explored using semiempirical quantum mechanical (SQM) methods. The dimer projection (DIPRO) method combined with the recently introduced non-self-consistent density matrix tight-binding potential (PTB) [Grimme et al., J. Chem. Phys. 158, 124111 (2023)] is used in this study to evaluate charge transfer integrals important for understanding charge transport mechanisms. PTB, parameterized for the entire Periodic Table up to Z = 86, incorporates approximate non-local exchange, allowing for efficient and accurate calculations for large hetero-organic compounds. Benchmarking against established databases, such as Blumberger's HAB sets, or our newly introduced JAB69 set and comparing with high-level reference data from ωB97X-D4 calculations confirm that DIPRO@PTB consistently performs well among the tested SQM approaches for calculating coupling integrals. DIPRO@PTB yields reasonably accurate results at low computational cost, making it suitable for screening purposes and applications to large systems, such as metal-organic frameworks and cyanine-based molecular aggregates further discussed in this work.

TBMaLT, a flexible toolkit for combining tight-binding and machine learning.

Tight-binding approaches, especially the Density Functional Tight-Binding (DFTB) and the extended tight-binding schemes, allow for efficient quantum mechanical simulations of large systems and long-time scales. They are derived from ab initio density functional theory using pragmatic approximations and some empirical terms, ensuring a fine balance between speed and accuracy. Their accuracy can be improved by tuning the empirical parameters using machine learning techniques, especially when information about the local environment of the atoms is incorporated. As the significant quantum mechanical contributions are still provided by the tight-binding models, and only short-ranged corrections are fitted, the learning procedure is typically shorter and more transferable as it were with predicting the quantum mechanical properties directly with machine learning without an underlying physically motivated model. As a further advantage, derived quantum mechanical quantities can be calculated based on the tight-binding model without the need for additional learning. We have developed the open-source framework-Tight-Binding Machine Learning Toolkit-which allows the easy implementation of such combined approaches. The toolkit currently contains layers for the DFTB method and an interface to the GFN1-xTB Hamiltonian, but due to its modular structure and its well-defined interfaces, additional atom-based schemes can be implemented easily. We are discussing the general structure of the framework, some essential implementation details, and several proof-of-concept applications demonstrating the perspectives of the combined methods and the functionality of the toolkit.

N-Methylimidazolidin-4-one organocatalysts: gas-phase fragmentations of radical cations by experiment and theory.

Electron ionisation mass spectra of N-methylimidazolidin-4-one organocatalysts were studied by experimental and theoretical means. The molecular ions mostly undergo alpha cleavages of exocyclic substituents that leave the five-membered ring intact. The type of substituent strongly dominates the appearance of the spectra. Fragmentation cascades are corroborated by metastable ion mass spectra. Quantum Chemistry Electron Ionisation Mass Spectra calculations correlate reasonably well with the experimental electron ionisation spectra and reveal mechanistic details of fragmentation pathways. The drawbacks and benefits of such calculations are discussed. Copyright © 2017 John Wiley & Sons, Ltd.

Synthesis of a monomolecular anionic FLP complex.

Despite intense research in FLP chemistry, nothing is known about monomolecular anionic FLPs and/or complexes thereof. Herein, synthesis and reaction of the first anionic FLP complex is described using [(OC)5W{(Me3Si)2HCP(H)OLi(12-crown-4)}], Cy2BCl and subsequent deprotonation by KHMDS. The obtained anionic FLP complex reacts readily with CO2 in a concerted manner.

Synthesis of novel pyridyl containing phospholanes and their polynuclear luminescent copper(i) complexes.

A novel type of cyclic P,N-ligands, pyridyl containing phospholanes, has been synthesized in a moderate yield by the reaction of primary phosphines with 1,4-dichlorobutane in a superbasic medium. A series of homo tetranuclear octahedral Cu4I4L2, dinuclear tetrahedral Cu2I2L3, and dinuclear "head-to-tail" Cu2I2L2 luminescent complexes with these ligands were obtained. All the compounds were characterized using a range of spectroscopic and computational techniques, and in the case of some Cu4I4L2 and Cu2I2L3 complexes, by single crystal X-ray diffraction. The structural diversity of the obtained complexes was reflected in their photophysical properties: phosphorescence spectra of the compounds display emission in broad spectral range of 471-615 nm. TD-DFT computations allow the assignment of a single emission band around 550 nm for Cu2I2L3 complexes and 471 nm for Cu2I2L2 complex to a vertical triplet-singlet transition from a metal-to-ligand and halide-to-ligand charge-transfer (3)(M + X)LCT excited state, whereas a second band at around 600 nm in the spectra of octahedral Cu4I4L2 complexes was assigned predominantly to Cu4I4 cluster-centered ((3)CC) excited state.

A comparative quantum chemical study of the ruthenium catalyzed olefin metathesis.

The accurate quantum mechanical description of homogeneous catalysis involving transition-metal complexes is a complicated and computationally demanding task. Hence, in this study the performance of different quantum chemical approaches with respect to the ruthenium catalyzed olefin metathesis of ethylene and RuCl(2)(PH(3))(2)CH(2) as a model system is investigated. All intermediates and transition states that are relevant for the rate determining steps of competing reaction mechanisms (associative and two dissociative pathways) are considered. Results from density functional theory calculations employing B-P86, B97-D, B3-LYP, TPSSh, and B2-PLYP functionals, as well as from MP2 and SCS-MP2 perturbation theory are compared to reference values (relative and reaction energies) obtained at the QCISD(T) level of theory. In particular, the applicability of AO basis sets of increasing size ranging from double-zeta to quadruple-zeta quality is evaluated for representative methods. For some reaction steps, large basis set effects on the order of 10 kcal mol(-1) (50% of Delta E) are observed. Double-zeta type basis sets yield very unreliable results while properly polarized triple-zeta sets provide reaction energies quite close to the basis set limit. The performance of recommended methods is B2-PLYP>TPSSh>B-86 approximately B97-D>SCS-MP2. The often used standard approaches B3-LYP and MP2 provide overall the largest errors. The accurate QCISD(T) computations predict in conclusion (and in agreement with a recent other study) that for the model system considered, the dissociative trans pathway is favored over the dissociative cis pathway and also over the associative reaction mechanism.

Stereoelectronic Substituent Effects in Saturated Main Group Molecules: Severe Problems of Current Kohn-Sham Density Functional Theory.

The Hartree-Fock method, two common density functionals (PBE and B3LYP), and two new functionals (B97-D and B2PLYP) together with very large AO basis sets are used to compute the isomerization energies for substituted (R [Formula: see text] H, F, Cl) branched to linear alkanes and silanes. The results of accurate SCS-MP2 computations are taken as reference. These reactions are an important test of how nonlocal electron correlation effects on medium-range lengths scales in saturated molecules are treated by approximate quantum chemical methods. It is found that the unacceptably large errors observed previously for hydrocarbons persist also for the here considered more polar systems. Although the B97-D and B2PLYP functionals provide improved energetics, the problem is not fully solved, and thus these systems are suggested as mandatory benchmarks for future density functionals.

Systematic quantum chemical study of DNA-base tautomers.

The relative energies of the energetically low-lying tautomers of pyridone, cytosine, uracil, thymine, guanine, and iso-cytosine are studied by a variety of different quantum chemical methods. In particular, we employ density functional theory (DFT) using the six functionals HCTH407, PBE, BP86, B-LYP, B3-LYP, and BH-LYP, and the ab initio methods Hartree-Fock (HF), standard second-order Møller-Plesset perturbation theory (MP2), an improved version of it (SCS-MP2), and quadratic configuration interaction including single and double excitations (QCISD) and perturbative triple corrections [QCISD(T)]. A detailed basis set study is performed for the formamide/formamidic acid tautomeric pair. In general, large AO basis sets of at least valence triple-zeta quality including f-functions (TZV) are employed, which are found to be necessary for an accurate energetic description of the various structures. The performance of the more approximate methods is evaluated with QCISD(T)/TZV(2df,2dp) data taken as reference. In general it is found that DFT is not an appropriate method for the problem. For the tautomers of pyridone and cytosine, most density functionals, including the popular B3-LYP hybrid, predict a wrong energetic order, and only for guanine, the correct sequence of tautomers is obtained with all functionals. Out of the density functionals tested, BH-LYP, which includes a rather large fraction of HF exchange, performs best. A consistent description of the nonaromatic versus aromatic tautomers seems to be a general problem especially for pure, nonhybrid functionals. Tentatively, this could be assigned to the exchange potentials used while the functional itself, including the correlation part, seems to be appropriate. Out of the ab initio methods tested, the new SCS-MP2 approach seems to perform best because it effectively reduces some outliers obtained with standard MP2. It outperforms the much more costly QCISD method and seems to be a very good compromise between computational effort and accuracy.

The essential Smp3 protein is required for addition of the side-branching fourth mannose during assembly of yeast glycosylphosphatidylinositols.

The major glycosylphosphatidylinositols (GPIs) transferred to protein in mammals and trypanosomes contain three mannoses. In Saccharomyces cerevisiae, however, the GPI transferred to protein bears a fourth, alpha1,2-linked Man on the alpha1,2-Man that receives the phosphoethanolamine (EthN-P) moiety through which GPIs become linked to protein. We report that temperature-sensitive smp3 mutants accumulate a GPI containing three mannoses and that smp3 is epistatic to the gpi11, gpi13, and gaa1 mutations, which normally result in the accumulation of Man(4)-GPIs, including the presumed substrate for the yeast GPI transamidase. The Smp3 protein, which is encoded by an essential gene, is therefore required for addition of the fourth Man to yeast GPI precursors. The finding that smp3 prevents the formation of the Man(4)-GPI that accumulates when addition of EthN-P to Man-3 is blocked in a gpi13 mutant suggests that the presence of the fourth Man is important for transfer of EthN-P to Man-3 of yeast GPIs. The Man(3)-GPI that accumulates in smp3 is a mixture of two dominant isoforms, one bearing a single EthN-P side branch on Man-1, the other with EthN-P on Man-2, and these isoforms can be placed in separate arms of a branched GPI assembly pathway. Smp3-related proteins are encoded in the genomes of Schizosaccharomyces pombe, Candida albicans, Drosophila melanogaster, and Homo sapiens and form a subgroup of a family of proteins, the other groups of which are defined by the Pig-B(Gpi10) protein, which adds the third GPI mannose, and by the Alg9 and Alg12 proteins, which act in the dolichol pathway for N-glycosylation. Because Man(4)-containing GPI precursors are normally formed in yeast and Plasmodium falciparum, whereas addition of a fourth Man during assembly of mammalian GPIs is rare and not required for GPI transfer to protein, Smp3p-dependent addition of a fourth Man represents a target for antifungal and antimalarial drugs.

High level ab initio calculations of the optical gap of small silicon quantum dots.

Using state of the art time-dependent density functional theory and multireference second-order perturbation theory, we have accurately calculated (within 0.3 eV) in real space the optical gap of small silicon quantum dots, with diameters up to 25 A. Our results, which support the quantum confinement hypothesis, are in excellent agreement with recent and earlier experimental data on oxygen-free samples and the conclusions of Wilcoxon et al. [Phys. Rev. B 60, 2704 (1999)]. We have found that the diameter of the smallest dot, which could emit photoluminescence in the visible region of the spectrum, is around 22 A. Our work can resolve existing controversies and bridge diverse experimental and theoretical results.

Endocytosis of insulin-like growth factor II by a mini-receptor based on repeat 11 of the mannose 6-phosphate/insulin-like growth factor II receptor.

The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II receptor) plays an important role in controlling the extracellular level of the insulin-like growth factor II (IGF-II) by mediating its binding at the cell surface and delivery to lysosomes. Loss of the receptor is associated with an accumulation of IGF-II, which can cause perinatal lethality if it is systemic, or local proliferation and tumorgenesis if it is spatially restricted. The extracytoplasmic domain of the receptor consists of 15 homologous repeats, of which repeat 11 carries the IGF-II-binding site of the multifunctional receptor. To investigate whether repeat 11 is sufficient to mediate binding and internalization of IGF-II, a construct consisting of repeat 11 fused to the transmembrane and cytoplasmic domain of the M6P/IGF-II receptor was transfected into mouse embryonic fibroblasts. The construct was expressed as a stable membrane protein which binds IGF-II with a 10-fold lower affinity as observed for the M6P/IGF-II receptor and is found at the cell surface and in endosomes. It mediates the internalization of IGF-II and its delivery to lysosomes, suggesting that it can function as a IGF-II mini-receptor controlling the extracellular IGF-II level.

Glycosylphosphatidylinositol biosynthesis defects in Gpi11p- and Gpi13p-deficient yeast suggest a branched pathway and implicate gpi13p in phosphoethanolamine transfer to the third mannose.

Glycosylphosphatidylinositols (GPIs) are critical for membrane anchoring and intracellular transport of certain secretory proteins. GPIs have a conserved trimannosyl core bearing a phosphoethanolamine (EthN-P) moiety on the third mannose (Man-3) through which the glycolipid is linked to protein, but diverse GPI precursors with EthN-Ps on Man-1 and Man-2 have also been described. We report on two essential yeast genes whose products are required late in GPI assembly. GPI11 (YDR302w) encodes a homologue of human Pig-Fp, a protein implicated in the addition of EthN-P to Man-3. PIG-F complements the gpi11 deletion, but the rescued haploids are temperature sensitive. Abolition of Gpi11p or Pig-Fp function in GPI11 disruptants blocks GPI anchoring and formation of complete GPI precursors and leads to accumulation of two GPIs whose glycan head groups contain four mannoses but differ in the positioning and number of side chains, probably EthN-Ps. The less polar GPI bears EthN-P on Man-2, whereas the more polar lipid has EthN-P on Man-3. The latter finding indicates that Gpi11p is not required for adding EthN-P to Man-3. Gpi13p (YLL031cp), a member of a family of phosphoryltransferases, is a candidate for the enzyme responsible for adding EthN-P to Man-3. Depletion of Gpi13p in a Gpi11p-defective strain prevents formation of the GPI bearing EthN-P on Man-3, and Gpi13p-deficient strains accumulate a Man(4)-GPI isoform that bears EthN-P on Man-1. We further show that the lipid accumulation phenotype of Gpi11p-deficient cells resembles that of cells lacking Gpi7p, a sequence homologue of Gpi13p known to add EthN-P to Man-2 of a late-stage GPI precursor. This result suggests that in yeast a Gpi11p-deficiency can affect EthN-P addition to Man-2 by Gpi7p, in contrast to the Pig-Fp defect in mammalian cells, which prevents EthN-P addition to Man-3. Because Gpi11p and Pig-Fp affect EthN-P transfer to Man-2 and Man-3, respectively, these proteins may act in partnership with the GPI-EthN-P transferases, although their involvement in a given EthN-P transfer reaction varies between species. Possible roles for Gpi11p in the supply of the EthN-P donor are discussed. Because Gpi11p- and Gpi13p-deficient cells accumulate isoforms of Man(4)-GPIs with EthN-P on Man-2 and on Man-1, respectively, and because the GPIs that accumulate in Gpi11p-defective strains are likely to have been generated independently of one another, we propose that the yeast GPI assembly pathway is branched.

Characterization of cobalt(II)-substituted peptide deformylase: function of the metal ion and the catalytic residue Glu-133.

Peptide deformylase (PDF) catalyzes the hydrolytic removal of the N-terminal formyl group from nascent ribosome-synthesized polypeptides in eubacteria. PDF represents a novel class of mononuclear iron protein, which utilizes an Fe(2+) ion to catalyze the hydrolysis of an amide bond. This Fe(2+) enzyme is, however, extremely labile, undergoing rapid inactivation upon exposure to molecular oxygen, and is spectroscopically silent. In this work, we have replaced the native Fe(2+) ion with the spectroscopically active Co(2+) ion through overexpression in the presence of Co(2+). Co(2+)-substituted PDF (Co-PDF) has an activity 3-10-fold lower than that of the Fe(2+)-PDF but is highly stable. Steady-state kinetic assays using a series of substrates of varying deformylation rates indicate that Co-PDF has the same substrate specificity as the native enzyme. Co-PDF and Fe-PDF also share the same three-dimensional structure, pH sensitivity, and inhibition pattern by various effector molecules. These results demonstrate that Co-PDF can be used as a stable surrogate of Fe-PDF for biochemical characterization and inhibitor screening. The electronic absorption properties of the Co(2+) ion were utilized as a probe to monitor changes in the enzyme active site as a result of site-directed mutations, inhibitor binding, and changes in pH. Mutation of Glu-133 to an alanine completely abolishes the catalytic activity, whereas mutation to an aspartate results in only approximately 10-fold reduction in activity. Analysis of their absorption spectra under various pH conditions reveals pK(a) values of 6.5 and 5.6 for the metal-bound water in E133A and E133D Co-PDF, respectively, suggesting that the metal ion alone is capable of ionizing the water molecule to generate the catalytic nucleophile, a metal-bound hydroxide. On the other hand, substrate binding to the E133A mutant induces little spectral change, indicating that in the E.S complex the formyl carbonyl oxygen is not coordinated with the metal ion. These results demonstrate that the function of the active-site metal is to activate the water molecule, whereas Glu-133 acts primarily as a general acid, donating a proton to the leaving amide ion during the decomposition of the tetrahedral intermediate.

MCD4 encodes a conserved endoplasmic reticulum membrane protein essential for glycosylphosphatidylinositol anchor synthesis in yeast.

Glycosylphosphatidylinositol (GPI)-anchored proteins are cell surface-localized proteins that serve many important cellular functions. The pathway mediating synthesis and attachment of the GPI anchor to these proteins in eukaryotic cells is complex, highly conserved, and plays a critical role in the proper targeting, transport, and function of all GPI-anchored protein family members. In this article, we demonstrate that MCD4, an essential gene that was initially identified in a genetic screen to isolate Saccharomyces cerevisiae mutants defective for bud emergence, encodes a previously unidentified component of the GPI anchor synthesis pathway. Mcd4p is a multimembrane-spanning protein that localizes to the endoplasmic reticulum (ER) and contains a large NH2-terminal ER lumenal domain. We have also cloned the human MCD4 gene and found that Mcd4p is both highly conserved throughout eukaryotes and has two yeast homologues. Mcd4p's lumenal domain contains three conserved motifs found in mammalian phosphodiesterases and nucleotide pyrophosphases; notably, the temperature-conditional MCD4 allele used for our studies (mcd4-174) harbors a single amino acid change in motif 2. The mcd4-174 mutant (1) is defective in ER-to-Golgi transport of GPI-anchored proteins (i.e., Gas1p) while other proteins (i.e., CPY) are unaffected; (2) secretes and releases (potentially up-regulated cell wall) proteins into the medium, suggesting a defect in cell wall integrity; and (3) exhibits marked morphological defects, most notably the accumulation of distorted, ER- and vesicle-like membranes. mcd4-174 cells synthesize all classes of inositolphosphoceramides, indicating that the GPI protein transport block is not due to deficient ceramide synthesis. However, mcd4-174 cells have a severe defect in incorporation of [3H]inositol into proteins and accumulate several previously uncharacterized [3H]inositol-labeled lipids whose properties are consistent with their being GPI precursors. Together, these studies demonstrate that MCD4 encodes a new, conserved component of the GPI anchor synthesis pathway and highlight the intimate connections between GPI anchoring, bud emergence, cell wall function, and feedback mechanisms likely to be involved in regulating each of these essential processes. A putative role for Mcd4p as participating in the modification of GPI anchors with side chain phosphoethanolamine is also discussed.

Deoxycytidine kinase and deoxyguanosine kinase of Lactobacillus acidophilus R-26 are colinear products of a single gene.

Three of the four deoxynucleoside kinases required for growth of Lactobacillus acidophilus R-26 exist as heterodimeric pairs specific for deoxyadenosine (dAK) and deoxycytidine (dCK) or dAK and deoxyguanosine (dGK). However, only two tandem genes, dak/dgk, are found, and are expressed only as dAK/dGK in transformed Escherichia coli. Sequencing peptides spanning 63% of the native dCK subunit revealed a sequence identical to that deduced from dgk (beginning MTVIVL...), except that dCK lacks residues 2 and 3 (dCK is M..IVL; dGK is .TVIVL). Also, mass spectrometry indicates that native dCK and dGK subunits are identical in mass adjusted for the first three residues. Furthermore, the native enzymes have identical isoelectric pH values, indicating an equal number of charged residues. To enable E. coli to express peptide having the native dCK sequence, codons 2 and 3 were deleted from the dgk portion of the tandem genes, resulting in expression of protein having the specificities and regulatory properties of native dAK/dCK, including heterotropic stimulation of dAK activity by deoxycytidine or dCTP (not deoxyguanosine or dGTP) and end-product inhibition of the respective activities by dATP and dCTP. Subcloning normal and mutant dgk yielded homodimeric dGK and dCK, respectively. The dCK homodimer strongly resembles human dCK, with a low K(m) for deoxycytidine, the ability to phosphorylate deoxyadenosine and deoxyguanosine at much higher K(m) values, and end-product inhibition by dCTP. Thus two distinct and specific enzymes evidently are derived from a single Lactobacillus gene. The mechanism by which this occurs in vivo has yet to be elucidated.

A highly sensitive, nonradioactive DNA labeling and detection system.

A highly sensitive method for detecting specific nucleotide sequences was recently developed. The method uses digoxigenin-labeled nucleic acid probes for hybridization to immobilized target nucleic acids. Probes can be labeled by the random-primed method, nick translation, oligonucleotide tailing, cDNA synthesis, photodigoxigenin or SP6/T7/T3 polymerase-mediated transcription. Hybrids are detected by an enzyme-linked immunoassay using an anti-digoxigenin antibody conjugate. Visualization of the bound antibody is accomplished by an enzymatic color reaction, enzymatic chemiluminescent reaction or immunofluorescence, depending on the antibody conjugate and enzymatic substrate used. Here we report the successful application of this technology in the detection of specific cloned DNA in colony and plaque hybridizations, specific detection of a single mRNA species in Northern blots and single-copy gene detection in genomic Southern blots.