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Biomedical subjects

H Basch

Publications and source records attributed to H Basch.

11 recordsLinked to original sources
PubMed2005

Interface geometry and molecular junction conductance: geometric fluctuation and stochastic switching.

Metal/molecule/metal transport junctions can transport charge in the elastic scattering (Landauer) regime if the injection gap is large and the molecule is relatively short. Stochastic switching and broad conduction peak distributions have been observed in such junctions. We examine the effect of altering interface geometry on transport, using density functional calculations. For most structures, variations in conductance of order 0-300% are found, but when an atomic wire of Au binds to the molecule, symmetry changes can modify currents by a factor of 10(3).

Journal Article↗
PubMed2001

Quantification of the various contributors to rate enhancement in nucleophilic strain releasing reactions.

Since cyclopropanes are much more reactive than cyclobutanes despite their nearly identical strain energy, it has become clear that rate enhancement in cyclopropanes is partly due to strain release but also partly due to an additional factor about whose nature there is no consensus. Activation and equilibrium energies for a series of nucleophilic reactions of MeO-, MeS-, MeNH-, Me2N-, and MePH- with strained rings ranging from epoxide to aza-cubane were computed at the HF/631 + G* level. Using the Marcus equation, in combination with the computed intrinsic barrier for the identity reactions of the same nucleophiles with the strain free reference compounds (e.g., MeO- with Me-O-Me and Me2N- with Me3N), enabled a quantitative determination of the individual contributions of the partial strain release and the additional factor to the overall lowering of the transition state energy. Analysis of the data reveals the following: (a) There is no contribution of the additional factor to rate enhancement in four membered rings for first row elements (O and N) and only a small contribution (approximately 2 kcal) for second row elements (S and P). This is to be compared with a contribution of 7-17 kcal for three membered rings. (b) A significant synergistic effect is observed. Thus, in housane, for example, the additional factor amounts to 12.7 kcal which is more (by nearly 5 kcal) than the sum of the individual contributions of the isolated three and four membered rings. (c) The magnitude of the additional factor was found to be Periodic Table row dependent.

Journal Article↗
PubMed1985

A theoretical model for the binding of cis-Pt(NH3)2(+2) to DNA.

The binding of cis-Pt(NH3)2B1B2 to the bases B1 and B2, i.e., guanine (G), cytosine (C), adenine (A), and thymine (T), of DNA is studied theoretically. The components of the binding are analyzed and a model structure is proposed for the intrastrand binding to the dB1pdB2 sequence of a kinked double helical DNA. Quantum mechanical calculations of the ligand binding energy indicates that cis-Pt(NH3)2(+2) (cis-PDA) binds to N7(G), N3(C), O2(C), O6(G), N3(A), N7(A), O4(T) and O2(T) in order of decreasing binding energy. Conformational analysis provides structures of kinked DNA in which adjacent bases chelate to cis-PDA. Only bending toward the major groove allows the construction of acceptable square planar complexes. Examples are presented for kinks of -70 degrees and -40 degrees at the receptor site to orient the base pairs for ligand binding to B1 and B2 to form a nearly square planar complex. The energies for complex formation of cis-PDA to the various intra-strand base sites in double stranded DNA are estimated. At least 32 kcal/mole separates the energetically favorable dGpdG.cis-PDA chelate from the dCpdG.cis-PDA chelate. All other possible chelate structures are much higher in energy which correlates with their lack of observation in competition with the preferred dGpdG chelate. The second most favorable ligand energy occurs with N3(C). A novel binding site involving dC(N3)pdG(N7) is examined. Denaturation can result in an anti----syn rotation of C about its glycosidic bond to place N3(C) in the major groove for intrastrand binding in duplex DNA. This novel intrastrand dCpdG complex and the most favored dGpdG structure are illustrated with stereographic projections.

Base Sequence↗
PubMed1971

Epicillin: in vitro laboratory studies.

A new semisynthetic penicillin, structurally related to ampicillin, has been assigned the generic name epicillin, 6-[d-2-amino-2-(1, 4-cyclohexadienyl) acetamido]-penicillanic acid. The antimicrobial spectrum and level of activity of epicillin in vitro are similar to those of ampicillin. In studies with recent clinical isolates, these two antibiotics, when compared with carbenicillin, showed consistently higher antimicrobial activity against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Proteus species. When tested against Pseudomonas aeruginosa isolates, on the other hand, epicillin exhibited a level of intrinsic activity superior to that of ampicillin but less than that of carbenicillin. Epicillin is an amphoteric substance that is sensitive to penicillinase, is acid-stable, and is minimally, but reversibly, bound to human serum protein.

Acetamides↗
PubMedDate not supplied

The binding of substituted cis-Pt(II)-diammines to duplex DNA.

The results of a study of the binding to DNA of substituted cis-Pt(II) diammines, (cis-DP) are presented. Computer modeling of a series of cis-Pt(NH2R)2(+2)--where R = H, CH3, cyclopropyl, cyclobutyl, and cyclopentyl--to N7(G) atoms of two adjacent intrastrand guanine bases in a square planar complex in a pentamer duplex of DNA were performed. The stability of the complexes is studied by calculating the relative conformational energy of the cis-DP-DNA complexes with molecular mechanics (MM) and the intrinsic binding energy, which is the relative binding energy for ligand replacement in the presence of the substituents R with quantum mechanics. In the model, the receptor site geometry and the conformation of the DNA is changed little in the accommodation of the series of monosubstituted diammines. These diammines bind to one family of DNA conformations, denoted as IC in a previous study, and this suggests that a common conformational feature in the DNA may exist to explain the smooth trend in activity. The slight increase in van der Waals energy resulting from an increasing number of atoms in the substituents is countered by a larger decrease in the ligand replacement energy as the substituent increases in size. This overall decrease in relative energy is consistent with the slight decrease in activity as the substituent size increases.

Binding Sites↗
PubMedDate not supplied

Theoretical studies of cis-Pt(II)-diammine binding to duplex DNA.

The binding of cis-Pt(II) diammine (cis-DP) to double-stranded DNA was studied with several kinked conformations that can accommodate the formation of a square planar complex. Molecular mechanics (MM) calculations were performed to optimize the molecular fit. These results were combined with quantum mechanical (QM) calculations to ascertain the relative energetics of ligand binding through water vs direct binding of the phosphate to the ammine and platinum, and to guide the selection of DNA conformations to model complex formation. Based on QM and MM calculations, models are proposed that may be characterized by several general features. A structure involving hydrogen bonding between each ammine and distinct adjacent phosphate groups, referred to as closed conformation (CC), has already been reported. This is also found in the crystal structure of small dimers. We report alternative conformations that may be important in platination of duplex DNA. They are characterized by an intermediate conformation (IC), involving hydrogen bonding between one ammine and phosphate group, and an open conformation (OC), without ammine phosphate hydrogen bonding. The IC and OC can be stabilized by water bridges in the space between the ammine and the phosphate groups. Sugar puckers alternate from the type C(2')-endo or C(1')-exo (S), to the type C(3')-endo or C(2')-exo (N), with intermediate types near O(1')-endo (O). In general, the sugar puckers alternate from S to N to S through the platinated region (3'-TpG*pG*p-5'), with the complexed strand exhibiting, (3')-S*-N*-S-(5') alternation, while the complementary strand shows either (3')-S*-N*-S-(5') or (3')-S*-N*-O-(5') alternation. In both the OC and IC, a hydrogen bond is found between the ammine and O4(T) on thymine (T) at the (3') end, adjacent to the complex site. There is a continuous range of backbone conformations through the platinated region which relate the OC to the IC. The models presented suggest that the dynamics of the binding of the cis-Pt(II)-diammines to adjacent N7(G) in double-stranded DNA may encompass several conformational possibilities, and that water bridges may play a roll in supporting open and intermediate conformations. Proton-proton distances are reported to assist in the experimental determination of conformations.

Cisplatin↗