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The U.S. Environmental Protection Agency’s (EPA) Water Laboratory Alliance relies on the Centers for Disease Control and Prevention’s ultrafiltration-based Water Processing Procedure (WPP) for concentration of biosafety level 3 (BSL-3) agents from 10 L to 100 L of drinking water. The WPP requires comprehensive training and practice to maintain proficiency, resulting in a critical need for quality control (QC) criteria. The aim of this study was to develop criteria using male-specific (MS2) coliphage (BSL-2 agent) to minimize safety hazards associated with BSL-3 agents and to use the criteria to evaluate analytical proficiency during a demonstration exercise. EPA Method 1602 with EasyPhage was used during the study to develop QC criteria for 100-mL, and 40–100 L samples. The demonstration exercise indicated that the MS2 criteria would allow laboratories to demonstrate proficiency using the WPP with 40–100 L samples. In addition, the QC criteria developed for 100-mL samples has broad applicability at laboratories that are using MS2 for other types of analyses, such as assessment of water treatment devices. The development of MS2 QC criteria allows laboratories to develop and confirm ongoing proficiency using the WPP.

Binding positions, conformations, and relative minimum binding energies of thioxanthenones, lucanthone, and N-methyllucanthone are calculated for intercalation complexes with DNA in the theoretically determined principal intercalation sites I and II. The optimum binding position of thioxanthenone is identical to that for the chromophore in lucanthone and in its N-methyl derivative. Intercalative binding is optimized in lucanthone and N-methyllucanthone because the chromophore is not disrupted by substituents, and the amino side chain conforms to the phosphate backbone without an increase in conformational energy over that of the free molecule. N-methyl substitution of lucanthone results in a reorientation of the NCH2-CH2NH(+)(CH2CH3)2 substituent and a net loss in electrostatic energy resulting in a decrease of 17.9 kcal in the total binding energy. This result is consonant with the experimental observation that N-methyllucanthone does not intercalate into DNA, whereas lucanthone does. Specificity for base pair sequences in intercalation complexes with lucanthone is attributed primarily to the energy required to open B-DNA to an intercalation site and secondarily to the orientation of the terminal protonated nitrogen toward the carbonyl oxygen on cytosine. Both of these effects enhance the preference for one base. Because the distribution of base pairs G-C and A-T in all 16 dimer duplex intercalation complexes is uniform throughout the range of energy of the complexes, base pair specificity should not be observed for a random distribution of G-C and A-T. However, there is a sequence specificity for synthetic DNA in the order of decreased binding: poly(dC)-poly(dG) > poly(dA-dT)-poly(dA-dT) > poly(dG-dC)-poly(dG-dC) > poly(dA)-poly(dT).

Differential cross sections for the atomic transitions 2p)ns) and 2p)np) are studied within the First Born Approximation by using a one-electron model based on hydrogen-like orbitals with appropriate effective nuclear charges. For single electron excitations, the related dimensionless quantity, the generalized oscillator strength, can be scaled to yield f(k) which depends upon the ratio of effective nuclear charges and reduced momentum transfer k. Calculations of f(k) versus k show that Rydberg series exhibit in f(k) extrema which are nearly the same for all members of the series, whereas excitations to different series exhibit a different number and positioning of the extrema. These trends suggest that patterns in generalized oscillator strengths can be used as an experimental tool to probe various types of transitions and to unravel Rydberg series. Comparison of theoretical values with available experimental results indicates close agreement.

Molecular systems are partitioned into subsystems. A general theorem is developed which relates the total molecular secular equation to the characteristic polynomials of these molecular subsystems. To selectively study subsystems of chemical interest, the linked substituents are approximated by a perturbing single-centered atomic-like substituent called a pseudo substituent. A criterion for replacement by pseudo substituent representations is developed. The transferability of pseudo substituent representations to different molecules facilitates complete molecular studies. A perturbing potential for the pseudo substituent replacement is proposed.

The U.S. Environmental Protection Agency's (EPA) Water Laboratory Alliance (WLA) currently uses ultrafiltration (UF) for concentration of biosafety level 3 (BSL-3) agents from large volumes (up to 100-L) of drinking water prior to analysis. Most UF procedures require comprehensive training and practice to achieve and maintain proficiency. As a result, there was a critical need to develop quality control (QC) criteria. Because select agents are difficult to work with and pose a significant safety hazard, QC criteria were developed using surrogates, including Enterococcus faecalis and Bacillus atrophaeus. This article presents the results from the QC criteria development study and results from a subsequent demonstration exercise in which E. faecalis was used to evaluate proficiency using UF to concentrate large volume drinking water samples. Based on preliminary testing EPA Method 1600 and Standard Methods 9218, for E. faecalis and B. atrophaeus respectively, were selected for use during the QC criteria development study. The QC criteria established for Method 1600 were used to assess laboratory performance during the demonstration exercise. Based on the results of the QC criteria study E. faecalis and B. atrophaeus can be used effectively to demonstrate and maintain proficiency using ultrafiltration.

Designing and conducting standardized microbiological method interlaboratory validation studies is challenging because most methods are manual, rather than instrument-based, and results from the methods are typically subjective. Determinations of method recovery, in particular, are problematic, due to difficulties in assessing the true spike amount. The standardization and validation process used for the seven most recent USEPA 1600-series pathogen monitoring methods has begun to address these challenges. A staged development process was used to ensure that methods were adequately tested and standardized before resources were dedicated to interlaboratory validation. The interlaboratory validation studies for USEPA Method 1622, for Cryptosporidium, USEPA Method 1601 for coliphage, and USEPA Method 1605 for Aeromonas assessed method performance using different approaches, due the differences in the nature of the target analytes and the data quality needs of each study. However, the use of enumerated spikes in all of the studies allowed method recovery and precision to be assessed, and also provided the data needed to establish quantitative quality control criteria for the methods.

Background: Cells that form hair are among the body's most rapidly dividing cells, with each daughter cell becoming part of the hair shaft as it differentiates and lengthens. It follows that hair might contain concentrations of xenobiotics (environmental chemicals, therapeutic drugs, illicit substances, etc.) reflective of the concentration in blood at the time of division and onset of differentiation of cells that give rise to hair. Objective: This study was designed to gain insight into the passive incorporation of xenobiotics into hair. Methods: This study focused on the parameters of the passive partitioning of three agents, two water-soluble amino acids (cysteine and glutamine) and codeine into hair. Undamaged black hair from various ethnic groups was incubated in solutions containing the three agents as a function of time and concentration. Hair was washed extensively; time and dose to steady state as well as partitioning coefficients were determined for each agent. Codeine washing with a pH gradient also was carried out. Results: Data show that the partitioning coefficient of the agents is linear but not stoichiometric. At low doses passive partitioning into hair is efficient, a 1 minute exposure leading to significant retention. Washing extensively with deionized water, the fluid used for passive partitioning of the test agent, will not reversibly extract all of the agent, regardless of race. Conclusion: Hair can effectively absorb and retain agents of the environment, and this retention occurs via mechanisms other than those inherent to an ion exchange column.

The radiation-induced decomposition of syndiotatic (st) and isostatic (it) poly(methyl methacrylate) (PMMA) to yield irradiation products (PMMA(d)) resulting from hydrogen abstraction from alpha-methyl or methylene groups to form main chain (M[double bond]) or side chain (S[double bond]) double bonds is studied by conformational analysis. Relative minimum energy conformations of the st- and it-isomers of PMMA as free molecules are studied. The isomers of PMMA(d) have relative minima in an overall linear (L) chain as well as a global minimum in a bent (B) form. The impact of the change of a tetrahedral C atom to a trigonal C atom upon double bond formation on the conformational energy is fundamental to the understanding of the results. The experimental results are explained by the following theoretical observations. In reactions involving only overall linear conformations, side chain double bond formation is favored because of the resulting large increase in steric repulsion between polymer units in main chain double bond formation. In reactions proceeding to bent conformations, however, the decreased steric interaction yields both main and side chain double bond formation within 6.3 kcal/mol for the st-PMMA(d) isomer and 2.2 kcal/mol for the it-PMMA(d) isomer. Reactions on surfaces are assumed to be constrained tomore » the overall linear conformation of the starting material, PMMA. Prevention of both M[double bond] and S[double bond] degradation products is desired for microlithographic applications. Increased solubility arising from main chain scission (MCS) is desired, and both M[double bond] and S[double bond] for that reason are undesirable with respect to resist sensitivity. It is proposed that the troublesome S[double bond] process can be attenuated or eliminated by replacing alpha-CH[sub 3] with alpha-CF[sub 3], thus enhancing the distribution of products toward MCS.« less

An empirical approach to estimate harmonic frequencies from experimental fundamental vibrational frequencies is presented. It is based on a partitioning of the eigenvectors of each normal mode, s = 1, 2, 3,…, 3N − 6, into internal motion components involving bond stretching, Bs, angle bending, As, torsional motion, Ts, and out-of-plane motion, Os. This is called the BATO method. An empirical function, f s = (1250B s + 2000A s + 1300T s + 1600O s ) A , is developed to assign relative anharmonic contributions to each kind of internal motion by relating harmonic frequencies, ωs, to the anharmonic or fundamental frequencies, νs, with νs = ωs + 2χs = ωs(1 − fsωs). The anharmonic states are assumed to satisfy a Morse expression, ν sn = ω s (n s + 1 2 ) + χ s (n s + 1 2 ) 2 , where ns = 0, 1, 2, ⋯ denote the vibrational states of mode s. The coefficients of fs are calibrated with the available experimental data for νsexp and ωsexp with isotopes of 19 molecules which contain bonds and groups required for biochemical applications. The objective is to use the BATO method to estimate empirical harmonic frequencies, ωsemp, from experimental fundamental frequencies, νsexp, in a self-consistent procedure in cases where ωsemp are not known. Of the 394 states in 19 molecules studied, the method yields results within 10 cm−1 for 232 states. 11–20 cm−1 for 86 states, 21–30 cm−1 for 45 states, 31–40 cm−1 for 19 states, 41–60 cm−1 for 9 states, and 61–81 cm−1 for 3 states tested. Detailed results are presented for the molecule containing the most common isotope. The maximum errors occur in C2H6 and C3H8, for which the method tends to overestimate the CH stretch in several cases where the comparison is against Dennison's rule. All molecules studied satisfy the product and summation rules well.

The U.S. Environmental Protection Agency has established several methods to delineate wellhead protection areas (WHPAs) around community wells in order to protect them from surface contamination sources. Delineating a WHPA often requires defining the capture zone for a well. Generally, analytical models or arbitrary setback zones have been used to define the capture zone in areas where little is known about the distribution of hydraulic head, hydraulic conductivity, or recharge. Numerical modeling, however, even in areas of sparse data, offers distinct advantages over the more simplified analytical models or arbitrary setback zones. The systematic approach discussed here calibrates a numerical flow model to regional topography and then applies a matrix of plausible recharge to hydraulic conductivity ratios (R/K) to investigate the impact on the size and shape of the capture zone. This approach does not attempt to determine the uncertainty of the model but instead yields several possible capture zones, the composite of which is likely to contain the actual capture zone. A WHPA based on this composite capture zone will protect ground water resources better than one based on any individual capture zone. An application of the method to three communities illustrates development of the R/K matrix and demonstrates that the method is particularly well suited for determining capture zones in alluvial aquifers.

Les calculs de mecanique moleculaire sont utilises pour modeliser les transitions du poly (p-xylylene) de la forme cristalline α a la forme condis β 1 , puis a la forme condis β 2 puis a l'etat fondu. Les parametres thermodynamiques correspondants sont calcules. Les conformations dans les differents etats sont discutees

Simplified formulas for first and second derivatives of the internal coordinates with respect to Cartesian coordinates are reported for linear and out-of-plane bending motion. They are expressed in a local coordinate system and then rotated to a space-fixed Cartesian coordinate system. For linear motion the important points are: (1) the invariance of the energy with respect to translational and rotational coordinate transformations and (2) the presentation of derivatives of the energy in terms of (α − π)2 rather than (α − π), where α is the bond angle, to avoid indeterminant forms. By factoring the second derivatives of the energy with respect to (α − π) and sinα, analysis in this local coordinate system avoids division by sinα as α → π. The formulas describe linear systems without the need to project the motion onto two perpendicular planes. When the angle is exactly π two degenerate directions arise, and the coordinate axes perpendicular to the axis of the linear sequence of atoms may be chosen arbitrarily. Further refinements and clarifications of methods reported previously to obtain matrix elements for linear and out-of-plane motion are presented.

A theoretical study is presented for the binding of RR, SS, SR, and RS isomers 1,2-diaminocyclohexane (DAC) or cis-PtII(DAC) to DNA. cis-PtII(DAC) is ligated to N7(G) on two adjacent intrastrand guanine bases in a kinked pentamer duplex of DNA (AT, CG*, CG*, GC, AT). The relative stability of the complexes is determined by calculating the relative conformational energy of the cis-PtII(DAC)(DNA) complexes with molecular mechanics (MM) and the intrinsic binding or ligation energy with quantum mechanics (QM). The results suggest that the RR and SS isomers of PtII(DAC) adducts with DNA are more stable than the SR/RS isomer by 1.7 kcal/mol relative to the cis-PtII(DAC(H2O)2 aquated species. Calculations on the overall stability of these isomers show that the SS and RR isomers are 6.5-8.2 kcal/mol more stable than the SR/RS isomers when bound to DNA, and this is attributed to differences in the strain energy in the DAC rings. The theoretical analyses of these compounds correlate a small differential activity with the trend in intrinsic binding energies. The RR isomer is more active in B16 melanoma cells, and the SS is most active in L1210 leukemia, and in general the RR and SS isomers are more active than the SR and RS in most cell types. The fact that the activity is DNA dependent suggests that excision or repair mechanisms may be taking place and that additional mechanistic steps beyond molecular modeling and quantum mechanical calculations are required to fully understand the activity. These studies of molecular fit of cis-PtII(DAC) to DNA are used to suggest substituted DAC compounds that may yield similar binding characteristics. Modifications to yield DAC derivatives are recommended in anticipation that they may also exhibit activity.

Molecular mechanics calculations on the isolated molecule are used in a discussion of the transitions of poly(diethylsiloxane) from the rigid crystal, α, to the condis crystal, β, at T d , to another mesophase, α m , at T i , and finally to the isotropic melt at T x

Escherichia coli is a routinely used microbiological indicator of water quality. To determine whether holding time and storage conditions had an effect on E. coli densities in surface water, studies were conducted in three phases, encompassing 24 sites across the United States and four commonly used monitoring methods. During all three phases of the study, E. coli samples were analyzed at time 0 and at 8, 24, 30, and 48 h after sample collection. During phase 1, when 4°C samples were evaluated by Colilert or by placing a membrane onto mFC medium followed by transfer to nutrient agar containing 4-methylumbelliferyl-β- d -glucuronide (mFC/NA-MUG), three of four sites showed no significant differences throughout the 48-h study. During phase 2, five of seven sites showed no significant difference between time 0 and 24 h by membrane filtration (mFC/NA-MUG). When evaluated by the Colilert method, five of seven sites showed no significant difference in E. coli density between time 0 and 48 h. During phase 3, 8 of 13 sites showed no significant differences in E. coli densities between time 0 and the 48-h holding time, regardless of method. Based on the results of these studies, it appears that if samples are held below 10°C and are not allowed to freeze, most surface water E. coli samples analyzed by commonly used methods beyond 8 h after sample collection can generate E. coli data comparable to those generated within 8 h of sample collection. Notwithstanding this conclusion, E. coli samples collected from surface waters should always be analyzed as soon as possible.

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.

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.

A new proposal for the crystal structure of it-PMMA is presented in which the unit cell consists of five straight-chain molecules, each with four polymer units in two combinations of cis-trans methacrylate groups, ctct... and cttt... sequences, in an end-centered monoclinic or an orthorhombic init cell.

An apparatus for simultaneous recording of six heating/cooling curves of metallic mixtures is described. Data are recorded using computer data acquisition and temperature-time data displayed and printed out for evaluation. A reasonable set of data for plotting the phase diagram for the tin-bismuth system can be obtained from heating curves alone in 20 minutes; slightly better data from cooling curves can be obtained in 45 minutes. This allows the experiment to be completed and discussed as part of a single lecture-laboratory period.

Matrix elements for the first and second derivatives of the internal coordinates with respect to Cartesian coordinates are reported for stretching, linear, nonlinear, and out-of-plane bending and torsional motion. Derivatives of the energy with respect to the Cartesian coordinates are calculated with the chain rule. Derivatives of the energy with respect to the internal coordinates are straightforward, but the calculation of the derivatives of the internal coordinates with respect to the Cartesian coordinates can be simplified by the following two steps outlined in this article. First, the number of terms in the analytical functions can be reduced or will vanish when the derivatives of the bond length, bond angle, and torsion angle are reported in a local coordinate system in which one bond lies on an axis and an adjacent bond lies in the plane of two axes or is projected onto perpendicular planes for linear and out-of-plane bending motion. Second, a simple rotation transforms these derivatives to the appropriate orientation in the space-fixed molecular coordinate system. Functions of the internal coordinates are invariant with respect to translation and rotation. The translational invariance and the symmetry of the second derivatives for a system with L atoms are used to select L-1- and L(L-1)/2-independent first and second derivatives, respectively, of which approximately half of the latter vanish in the local coordinate system. The rotational invariance permits the transformation of the simplified derivatives in the local coordinate system to any orientation in space. The approach outlined in this article simplifies the formulas by expressing them in a local coordinate system, identifies the most convenient independent elements to compute, from which the dependent ones are calculated, and defines a transformation to the space-fixed molecular coordinate system.

A theoretical model is proposed for the covalent binding of (+) 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene denoted by BPDE I(+), to N2 on guanine. The DNA must kink a minimum of 39 degrees to allow proper hybrid configurations about the C10 and N2 atoms involved in bond formation and to allow stacking of the pyrene moiety with the non-bonded adjacent base pair. Conservative (same sugar puckers and glycosidic angles as in B-DNA) and non-conservative (alternating sugar puckers as in intercalation sites) conformations are found and they are proposed structures in pathways connecting B-DNA, an intercalation site, and a kink site in the formation of a covalently intercalative bound adduct of BPDE I(+) to N2 on guanine. Stereographic projections are presented for (3') and (5') binding in the DNA. Experimental data for bending of DNA by BPDE, orientation of BPDE in DNA and unwinding of superhelical DNA is explained. The structure of a covalent intercalative complex is predicted to result from the reaction. Also, an anti----syn transition of guanine results in a structure which allows the DNA to resume its overall B-form. The only change is that guanine has been rotated by 200 degrees about its glycosidic bond so that the BPDE I(+) is bound in the major groove. The latter step may allow the DNA to be stored with an adduct which may produce an error in the genetic code.

A generalized procedure to generate nucleic acid structures is presented. In this procedure, the bases of a base pair are oriented first for characterization of particular DNA receptor sites. The resultant sites are then used in the study of specific molecule–DNA interactions. For example, intercalation sites, kinked DNA, and twisted and tilted bases are envisioned. Alterations of structures via anti syn orientations of bases, as well as crankshaft motion about collinear bonds, provide additional conformations without disrupting the overall backbone structure. These approaches to the generation of nucleic acid structures are envisioned as required in studies of the intercalation phenomenon, minor adjustments of DNA to accommodate denaturation, binding of carcinogens to DNA, complex formation of transition metals with DNA, and antitumor agents as ligands. For these base-pair and base orientations, backbone orientations are calculated by the AGNAS technique to yield physically meaningful conformations, namely, those conformations for which nonbonded contacts are favourable. A procedure is presented to generate dimer duplex units that are physically meaningful and to assemble these units into a polynucleotide duplex. Double helices that begin with B-DNA, undergo a transition to one of the above-mentioned receptor sites, and return to B-DNA can be assembled from a catalog of dimer duplexes. Stereographic projections of the various receptor sites already being used to model binding to DNA are presented.

Generalized oscillator strengths, oscillator strengths, and total cross sections are calculated within the first Born approximation for 1σg→nσu and nπu transitions in H2; for selected 2σu, 1πu, and 3σg to nπg, nπu, nσg, nσu, and nδg transitions in N2; and for the 1πg→nπu excitations in O2 in addition to transitions equivalent to those studied in N2. When compared with the corresponding experimental spin‐allowed excitations good agreement is obtained in most cases. The spheroidal potential approximation within the independent particle model (IPM) is analyzed as the source of the problem for several of the transitions in N2 and O2 which yield properties smaller than the experimental results by 2 orders of magnitude. The theoretical result, previously unreported, for the 1πu→1δg transition in N2 suggests that its intensity should be compared to the 1πu→1πg(b′←X) and that it corresponds to the e←X transition. The theoretical result for the 1πu→1δg transition in O2 for which there is no experimental data is al...

The binding positions and relative minimum binding energies are calculated for complexes of 9-aminoacridine, proflavine, N-methylphenanthridinium, and ethidium in theoretically determined intercalation sites in B-DNA (sites I and II) and in unconstrained dimer-duplex sites. The selection of site I in B-DNA by these compounds agrees with the theoretical interpretation of studies of unwinding angles in closed circular DNA in all cases but ethidium, which is predicted to select site II. The most stable binding positions of the acridines and ethidium in unconstrained dimer-duplex units agree with experimental results of intercalation complexes of dinucleoside monophosphate units. Base-pair specificity for Watson-Crick pairing is examined. The energy of an intercalation complex is partitioned into ΔE23, the energy required to open base pairs BP2 and BP3 in B-DNA to a site, and ΔEIn, the energy change when a free molecular intercalates. ΔE23 depends strongly on the base-pair sequence, whereas ΔEIn for the four molecules studied does not. The three most stable sequences contain (pyrimidine)p(purine) units, and this provides a rationale for the exclusive formation of crystals of intercalation complexes with these units. In spite of this selectivity, the distribution of GṁC and AṁT base pairs is equal for these three units and persists as the more unstable sequences are included. Therefore, specificity arises from the interaction between the base pairs and the 2′-deoxyribose 5′-monophosphate backbone for the opening of B-DNA to an intercalation site and not from the interaction between the chromophore and the DNA.

The mode of action of many antitumor agents entails the inhibition of nucleic acid synthesis. Because many of the drugs can intercalate, it is assumed that intercalation is an important step in the mechanism of biological activity. As intercalants contain a planar chromophore as an ingredient essential for intercalation, chromophores that should fit into DNA are desired. This is the main theme of this investigation. Binding to DNA of fundamental moieties, protonated pyridine, aniline, phenol, quinone, and 4H-thiopyran-4-one, is studied to determine their optimum placement in DNA. The optimum orientations for each moiety are superimposed to form polyaromatic systems that can intercalate in a manner in which functional groups on these chromophores are oriented as in the moieties themselves. Ideal intercalants proposed contain three and four fused ring system, have protonated ring nitrogen atoms located to maximize the electrostatic interactions with DNA, hydroxy and amino groups that can hydrogen bond to the OII and O5′ phosphate backbone atoms, and carbonyl and sulfur groups in the central position of the ring system to provide variations in the chromophore and to interact with the relatively positive region in the intercalation site. The optimum orientation occurs when the chromophore and the base pairs overlap to the maximum extent. The ideal intercalants are fundamentally of the type

A screened potential model (SPM) is formulated with Slater-type functions to reproduce the density of the electron shells. The orbital exponent for the valence shell is optimized to calibrate the SPM against experimental valence and Rydberg s and p energy levels for the alkali metals (Li, Na, and K) rare gases (He, Ne, Ar, and Kr), second-row atoms, and Cu, Zn, Mg, S, and Ga. The resulting one-electron wave functions are used to calculate the dipole and velocity forms of the oscillator strengths and 〈1/r3〉 for spin-orbit coupling. The excellent agreement with the averaged experimental results suggests that the SPM atomic orbitals are a good starting point for the evaluation of one-electron properties.

Generalized oscillator strengths $f(K)$ and total cross sections $\ensuremath{\sigma}$ are calculated within the first Born approximation for elastic scattering and for spin-allowed electronic transitions from the $3{s}^{2}3p$ ground state to the $3{s}^{2}\mathrm{nd}$ ($n=3, \dots{}, 7$), $3{s}^{2}4s$, and $3{s}^{2}4p$ Rydberg states. Exchange effects are included in the cross sections via the Bonham-Ochkur-Rudge approximations. Hartree-Fock and superposition-of-configurations (SOC) wave functions are utilized to examine their effect on $f(K)$ and $\ensuremath{\sigma}$. $f(K)'s$ obtained from SOC wave functions to varying accuracy are plotted and compared, and $\ensuremath{\sigma}'\mathrm{s}$ calculated with HF and SOC wave functions are presented. Results calculated with a one-electron model using scaled hydrogenic orbitals to generate the $f(K)$ are compared with those obtained with Hartree-Fock and SOC wave functions.

This study attempted to investigate the relationship between wage-earner status, occupational level, and job satisfaction. It was proposed that wage-earner status was a more important determinant of job satisfaction than sex. However, the findings of this study suggested that sex was a more important determinant of job satisfaction than wage-earner status, and occupational level was a better predictor of job satisfaction than either sex or wage-earner status.

Based on steric and electrostatic considerations, the prerequisites for binding to DNA via the intercalation mechanism are proposed. Steric contour energy curves are presented to demonstrate the region inaccessible to an intercalant. They are calculated with a 6-n (n = 14) potential. This method is a soft potential analog of an excluded-volume approach. Electrostatic contours on the steric surface illustrate the relatively positive and negative regions of the binding site. The principal intercalation sites, predicted to fit into B-DNA via a tetramer-duplex unit, and the unconstrained dimer-duplex units, obtained in crystal structures, are examined. These contours illustrate the requirements of size, conformation, and net atomic charges necessary for intercalation and optimum binding. Based on the limited space available for intercalation by the presence of the backbone and the maximum base-pair separation of 8.25 A, an Essential Metabolite Exclusion Hypothesis is presented.

Oscillator strengths, generalized oscillator strengths, and cross sections are calculated using Hartree−Fock wavefunctions for spin allowed electronic transitions from the 2b2(n) and 1b1(π) molecular orbitals to the nb2 (n = 3, 4, and 5), nb1 (n = 2 and 3) and na1 (n = 5,⋅⋅⋅,10) Rydberg series, and for the singlet → triplet 2b2) 2b1) transition. The first Born approximation is utilized in the calculation of f (K), and exchange contributions are included in the calculation of the total cross sections with the Born−Ochkur−Rudge modifications. Contour plots illustrating the radial and angular dependence of the orbitals are presented to substantiate the atomiclike character of the nb2 and nb1 orbitals and to demonstrate the mixture of atomiclike states which contribute to the na1 molecular orbitals. The qualitative shape and trends in the occurence of extrema in the generalized oscillator strengths are discussed for transitions to Rydberg series whose excited molecular orbitals possess a given atomiclike char...

A series of ring-alkoxylated and ring-hydroxylated analogues of lucanthone was prepared and tested for antitumor activity. The most biologically interesting members of this group were the 7-hydroxylucanthone derivatives, 50 and 51, which gave T/C values in the NCI P-388 antitumor screen of 188 and 265, respectively. The apparent association constants and delta Tm values for a number of analogue-DNA complexes were determined to ascertain whether there was any quantitative correlation with biological activity. The most that can be said is that intercalation may be a necessary but far from sufficient condition for antitumor activity.

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.

Hydrogen bonding stabilizes the binding of Pt ammine cations to oligonucleotides. Model calculations explore the energetics of the binding of the ammine to G (O6) in PtA 3 G (A = ammine, G = guanine) and the intermolecular binding of a carbonyl oxygen to the aremine in a complex of PtA 4 and formaldehyde as a model of binding to carbonyl sites in thymine. Hydrogen-bondig interaction to the G(O6) site is weak but permits the close approach of the O6 and H atoms. Intermolecular hydrogen bonding is strong, as expected for an optimal ionic hydrogen bond.

The stereoisomeric configurations of poly(2,5-tetraliydrofurandiyl), 1, and poly(2,3-tetrahydrofurandiyl), 2, have been investigated by conformational analysis. Similar results were obtained for 1 and 2, Threodiisotactic (tit) and erythrodisyndiotactic (est) configurations could form low energy helical conformations, whereas erythrodiisotactic (eit) and threodisyndiotactic (tst) configurations generally formed low energy linear conformations. Helical conformations of I placed oxygen atoms at the interior of the helices, but helical conformations of 2 placed oxygen atoms more toward the periphery. The results of ion-binding experiments are interpreted in terms of the results of conformational analysis. Ion-binding experiments are consistent with the suggestion that configurations that can form low energy, helical conformations with oxygen atoms at the interior of the helices could bind cations efficiently. Configurations that can form only low energy linear conformations, or that form helices with oxygen atoms toward the periphery of the helices, should be inefficient in binding cations.

The Denver Water Department has been supplying water to the Denver metropolitan area for more than half a century. The natural streams in the area contribute only about 123 X 106 m3 (100 000 acre-ft) per year to supply the area. This water is insufficient to meet the current and growing needs of the Denver metropolitan area. Over the years, therefore, the department has developed extensive transmountain diversions to augment the indigenous supply and is now delivering over 308 X 106 m3 (250 000 acre-ft) of water each year. Looking ahead to the turn of this century, Denver will surely see the day when the unconventional alternative of direct potable reuse must be part of the overall water supply program to meet the area's increasing needs.

An algorithm is developed that enables the routine determination of backbone conformations of nucleic acids. All atomic positions including hydrogen are specified in accord with experimental bond lengths and angles but with theoretically determined conformational angles. For two Watson-Crick base pairs at a separation of 3.38 A, and perpendicular to a common helical axis, minimum energy configurations are found for all 10 combinations at helical angles of α ∼ 36°–38°, corresponding to the B-DNA structure with C(2′)-endo sugar puckers. Backbone configurations exist only within the range 35.5° ⩽ α ⩽ 42°, which suggests the origin of the 10-fold helix. Calculated stacking energies for the B-DNA structure increases for each of the clustered groups of base pairs: G·C with G·C, G·C with A·T, and A·T with A·T, and they are in approximate agreement with experimental observations. The counter-clockwise helix is examined, and physically meaningful structures are found only when the helical axes of successive base pairs are disjointed.