Density matrix averaged atomic natural orbital (ANO) basis sets for correlated molecular wave functions

Summary Generally contracted basis sets for first row atoms have been constructed using the Atomic Natural Orbital (ANO) approach, with modifications for allowing symmetry breaking and state averaging. The ANOs are constructed by averaging over several atomic states, positive and negative ions, and atoms in an external electric field. The contracted basis sets give virtually identical results as the corresponding uncontracted sets for the atomic properties, which they have been designed to reproduce. The design objective has been to describe the ionization potential, the electron affinity, and the polarizability as accurately as possible. The result is a set of well-balanced basis sets for molecular calculations. The starting primitive sets are 8s4p3d for hydrogen, 9s4p3d for helium, and 14s9p4d3f for the heavier first row atoms.     

Certification of an animal feed reference material for the organochlorine pesticide contents: BCR CRM 115

 An animal feed reference material has been prepared and enriched with 15 organochlorine pesticides at levels close to the maximum residue limits set up in the European Directive 74/63/EEC. The homogeneity of the material has been assessed on the basis of the pesticide contents at a level of sample intake of 5 g. The one year stability study revealed an instability of heptachlor, o,p′-DDT, p,p′-DDT, α-HCH and γ-HCH (decrease in content) and p,p′-TDE (increase) at +37 °C; at +20 °C no instability could be demonstrated. The material has been certified in an interlaboratory certification study for: HCB (0.0194 mg/kg), β-HCH (0.023 mg/kg), γ-HCH (0.0218 mg/kg), heptachlor (0.019 mg/kg), γ-Chlordane (0.048 mg/kg), α-Endosulfan (0.046 mg/kg), Dieldrin (0.018 mg/kg), Endrin (0.046 mg/kg), o,p′-DDT (0.046 mg/kg) and p,p′-DDE (0.047 mg/kg). The α-HCH isomer, Aldrin, β-Heptachloro-epoxide, p,p′-DDT and p,p′-TDE could not be certified. The methods used for the certification are described as well as the major difficulties encountered in the study. Received: 1 July 1996/Revised: 14 October 1996/Accepted: 16 October 1996     

A theoretical study of the structure of tricarbonatodioxouranate

The results of a study on the ground states of tricarbonato complexes of dioxouranate using multiconfigurational second-order perturbation theory (CASSCF/CASPT2) are presented. The equilibrium geometries of the complexes corresponding to uranium in the formal oxidation states VI and V, [UO(2)(CO(3))(3)](4)(-) and [UO(2)(CO(3))(3)],(5)(-) have been fully optimized in D(3)(h)() symmetry at second-order perturbation theory (MBPT2) level of theory in the presence of an aqueous environment modeled by a reaction field Hamiltonian with a spherical cavity. The uranyl fragment has also been optimized at CASSCF/CASPT2, to obtain an estimate of the MBPT2 error. Finally, the effect of distorting the D(3)(h)() symmetry to C(3) has been investigated. This study shows that only minor geometrical rearrangements occur in the one-electron reduction of [UO(2)(CO(3))(3)](4)(-) to [UO(2)(CO(3))(3)],(5)(-) confirming the reversibility of this reduction.     

Polarized basis sets and the calculation of infrared intensities from nuclear electric shielding tensors

The idea of the basis set polarization which follows from the known dependence of basis set functions on the perturbation strength is applied to the calculation of the dipole moment derivatives with respect to nuclear displacements. The differentiation of the dipole moment function is replaced by the straightforward evaluation of derivatives of the intramolecular electric field with respect to the external electric field strength. The method and its efficiency are illustrated by a series of calculations of the dipole moment derivatives for the water molecule. Already a polarized basis set of 26 CGTO's derived from the minimal CGTO basis set provides fairly reasonable results.     

On the ordering of the ionization energies in N2: A MC SCF study of near-degeneracy effects

Single configuration SCF wavefunctions yield poor results for the order and relative energies of low-lying icnic states of N₂. A multi-configurational SCF (MC SCF) model which takes account of the near degeneracy of a small number of strongly and weakly occupied orbitals corrects the errors of the SCF approach. MC SCF results for N₂ predict the correct ordering and give reasonably accurate results for the three lowest ionization potentials.     

The structure and conformation of the tryptophanyl diketopiperazines cyclo(Trp–Trp)·C2H6SO and cyclo(Trp–Pro)

The structure and conformation of the cyclic dipeptides [cyclo(L-Trp–L-Trp)·C₂H₆SO] and cyclo(L-Trp–L-Pro) have been investigated with X-ray crystallographic and spectroscopic methods. Cyclo(L-tryptophanyl-L-tryptophanyl)·DMSO solvate crystallized in the space group P2 ₁2₁2₁ with cell dimensions a = 6.193(2), b = 11.545(3), c = 31.117(4) Å. The crystal structure is stabilized by four hydrogen bonds (three intermolecular hydrogen bonds and one intramolecular bond). The first intermolecular bond is between the oxygen of DMSO and the nitrogen of indole ring 2, in contrast to the second intramolecular hydrogen bond between the nitrogen of indole ring 1 and the oxygen of DMSO. The two remaining intermolecular hydrogen bonds are between the nitrogens of the DKP ring and the carbonyl oxygens of the DKP ring. The values of ^1A ₁ (–45.764) and ^1A ₂ (67.437) indicate an extended side chain conformation for Trp residue 1 (E_N) and a folded conformation for Trp residue 2. The DKP ring is more planar than in other cyclic dipeptide compounds (₁ = 11.414, ₁ = –7.516, ₂ = 12.471, and ₂ = –8.256). In cyclo(L-Trp–L-Trp) the C resonance of L-tryptophan (29.88 ppm) is shifted upfield 0.82 ppm when compared with the same resonance in cyclo(L-Trp–L-Gly) (30.7 ppm) and cyclo(L-Leu–L-Trp) (30.7 ppm). Two conformations of cyclo(Trp–Pro) crystallized in the space group P1 with cell dimensions a = 5.422(1), b = 9.902(1), c = 13.443(2) Å, = 80.42(1), = 78.61(1), and = 89.13(1)°. The conformation of the backbone and the orientation of the aromatic side chains for these conformers are very similar. The DKP rings for both conformers adopt a typical boat conformation in contrast to the flattened chair conformation observed for cyclo(Tyr–Pro) and cyclo(Phe–F-Pro). The tryptophan side chains of these conformers are folded towards the diketopiperazine (DKP) ring. The pyrrolidine ring for conformer 1 can be described as an envelope (Cs–C-endo) conformation in contrast to the pyrrolidine ring symmetry for conformer 2 which is an intermediate between C_s and C₂ rather than pure C_s for the proline ring with C-endo and C-exo with respect to C. The two prolyl rings are puckered at the -carbon atoms which deviate from the best planes defined by the four remaining atoms. The crystal structures are stabilized by four intermolecular hydrogens bonds. An intermolecular bond between the nitrogen of the indole ring (conformer 1) and the carbonyl oxygen of the DKP ring (conformer 2) was observed. The second hydrogen bond is between the nitrogen of the indole ring (conformer 2) and the carbonyl oxygen of the DKP ring (conformer 1). The last two hydrogens involve the carbonyl oxygens of the DKP rings and the nitrogens of the DKP rings [carbonyl oxygen of DKP ring (conformer 1)––––nitrogen of DKP ring (conformer 2); nitrogen of DKP ring (conformer 1)––––––carbonyl oxygen of DKP ring (conformer 2)].     

An extension of Janson's inequality

An upper bound for P[W = 0], where W is a sum of indicator variables with a special structure, which appears, for example, in subgraph counts in random graphs, is derived. Furthermore, its applications to a problem of k-runs and a random graph problem are given. The result is a generalization and an improvement of the well-known Janson's inequality. © 1996 John Wiley & Sons, Inc.     

Epigenetic Anti-Cancer Treatment With a Stabilized Carbocyclic Decitabine Analogue

5-Aza-2’-deoxycytidine (Decitabine, AzadC) is a nucleoside analogue, which is in clinical use to treat patients with myelodysplastic syndrome or acute myeloid leukemia. Its mode of action is unusual because the compound is one of the few drugs that act at the epigenetic level of the genetic code. AzadC is incorporated as an antimetabolite into the genome and creates covalent, inhibitory links to DNA methyltransferases (DNMTs) that methylate 2’-deoxycytidine (dC) to 5-methyl-dC (mdC). Consequently, AzadC treatment leads to a global loss of mdC, which presumably results in a reactivation of silenced genes, among them tumor suppressor and DNA damage response genes. Because AzadC suffers from severe instability, which limits its use in the clinic, a more sophisticated AzadC derivative would be highly valuable. Here, we report that a recently developed carbocyclic AzadC analogue (cAzadC) blocks DNMT1 in the AML cell line MOLM-13 as efficient as AzadC. Moreover, cAzadC has a surprisingly strong anti-proliferative effect and leads to a significantly higher number of double strand breaks compared to AzadC, while showing less off-target toxicity. These results show that cAzadC triggers more deleterious repair and apoptotic pathways in cancer cells than AzadC, which makes cAzadC a promising next generation epigenetic drug.