Determination and characterization of a transition structure for water–formaldehyde addition

Quantum mechanical calculations of the geometric, energetic, electronic, and vibrational features of a transition structure for gas-phase water–formaldehyde addition (FW1?) are described, and a new transition-structure search algorithm is presented. Basis-set-dependent effects are assessed by comparisons of computed properties obtained from self-consistent field (SCF) molecular orbital (MO) calculations with STO-3G, 4-31G, and 6-31G^** basis sets in the absence of electron correlation. The results obtained suggest that STO-3G-level calculations may be sufficiently reliable for the prediction of the transition structure of FW1? and for the transition structures of related carbonyl addition reactions. Moreover, the calculated activation energy for formation of FW1? from water and formaldehyde (?44 kcal mol^?1) is very similar in all three basis sets. However, the energy of formaldehyde hydration predicted by STO-3G (? ?45 kcal mol^?1) is about three times larger than that predicted by the other two basis sets, with the activation energy for dihydroxymethane dehydration also being too large in STO-3G. Calculated force constants in all three basis sets are generally too large, leading to vibrational frequencies that are also too large. However, uniformly scaled force constants (in internal coordinates) give much better agreement with experimental frequencies, scaled 4-31G force constants being slightly superior to scaled STO-3G force constants.     

Oxidation of polypropylene in benzene solution

The oxidation of both amorphous and crystalline polypropylene in benzene solution was studied at 100–130°C. tert-Butyl peroxide was used as an initiator. The kinetic behavior of the amorphous and crystalline forms differs slightly; the oxidation rate of the amorphous type is slower for a given polymer and initiator concentration. The oxidation rate of solutions of the crystalline form can be simply described by the expression: R₀ = 1.87 × 10¹³ exp {?29,000/RT} [t-Bu₂O₂]^0.58[polypropylene]^0.73, mole/l.-min. Product analyses of the oxidized solutions are incomplete, but the results do show that only ～40% of the absorbed oxygen is present as hydroperoxide. Further, much of the hydroperoxide is present in low molecular weight polar fragments which are acetone-soluble. These results show that oxidized polypropylene cannot be regarded simply as “polypropylene hydroperoxide” with repeating hydroperoxide groups attached to the polymer chain in 1,3,5… (tertiary) positions.     

Solution-phase parallel synthesis of a pharmacophore library of HUN-7293 analogues: a general chemical mutagenesis approach to defining structure-function properties of naturally occurring cyclic (depsi)peptides

HUN-7293 (1), a naturally occurring cyclic heptadepsipeptide, is a potent inhibitor of cell adhesion molecule expression (VCAM-1, ICAM-1, E-selectin), the overexpression of which is characteristic of chronic inflammatory diseases. Representative of a general approach to defining structure-function relationships of such cyclic (depsi)peptides, the parallel synthesis and evaluation of a complete library of key HUN-7293 analogues are detailed enlisting solution-phase techniques and simple acid-base liquid-liquid extractions for isolation and purification of intermediates and final products. Significant to the design of the studies and unique to solution-phase techniques, the library was assembled superimposing a divergent synthetic strategy onto a convergent total synthesis. An alanine scan and N-methyl deletion of each residue of the cyclic heptadepsipeptide identified key sites responsible for or contributing to the biological properties. The simultaneous preparation of a complete set of individual residue analogues further simplifying the structure allowed an assessment of each structural feature of 1, providing a detailed account of the structure-function relationships in a single study. Within this pharmacophore library prepared by systematic chemical mutagenesis of the natural product structure, simplified analogues possessing comparable potency and, in some instances, improved selectivity were identified. One potent member of this library proved to be an additional natural product in its own right, which we have come to refer to as HUN-7293B (8), being isolated from the microbial strain F/94-499709.     

Stereochemical assignments of the 7-phenyl-3-oxabicyclo[4.1.0]heptanes

A method for making stereochemical assignments based on nmr data for the 7-phenyl-3-oxabicyclo[4.1.0]-heptanes is described.     

Effects of glucose,glutamine, and malate on the metabolism of spodoptera frugiperda clone 9 (sf9) cells

Optimal design and operation of bioreactors for insect cell culture is facilitated by functional relations providing quantitative information on cellular metabolite consumption kinetics, as well as on the specific cell growth rates (μ_G). Initial specific consumption rates of glucose, malate, and oxygen, and associated changes in μ_G, were measured forSpodoptera frugiperda clone 9 (Sf9) cells grown in batch suspension culture in medium containing 7–35 mM glucose, 0–16 mM malate, and 4–16 mM glutamine. The initial specific glucose consumption rate (q _G ) could be described by a modified Michaelis-Menten equation treating malate as a “competitive” inhibitorK ₁ = 6.5 mM) and glutamine as a “noncompetitive” inhibitorK _I = 14 mM) ofq _G , with aK _m of 7.1 mM for glucose. All three carbon sources were found to increase μ_G in a saturable manner, and a modified Monod equation was employed to describe this relationship (μ_Gmax = 0.047 h^-1). The initial specific oxygen consumption rate (q_O2) in Sf9 cells could be related to μ_G by the maintenance energy model, and it was calculated that, under typical culture conditions, about 15–20% of the cellular energy demand comes from functions not related to growth. Fitted parameters in mathematical expression for μg: K₄, Monod constant for glucose (mM); K₅, modified Monod constant for malate (mM); K₆, Monod constant for glutamine (mM); m_o2, specific consumption rate of oxygen by the cells under zero-growth conditions (nmol/cell/h); q_F, initial specific fumarate production rate (nmol/cell/ h);q _G , initial specific glucose consumption rate (nmol/cell/h); q_Gmax, maximum initial specific glucose consumption rate (nmol/cell/h);q _M , initial specific malate consumption rate (nmol/cell/h); q_o2, initial specific oxygen consumption rate (nmol/cell/h); Y_o2, cell yield on oxygen (cells/nmol); μ, initial specific cell growth rate (h^-1); μ_g, initial specific cell growth rate (h^-1); μG_max, maximum initial specific cell growth rate (h^-1).     

Kinetics and mechanisms of S(IV) reductions of bromite and chlorite ions

The reaction of bromite with aqueous S(IV) is first order in both reactants and is general-acid catalyzed. The reaction half-lives vary from 5 ms (p[H+] 5.9) to 210 s (p[H+] 13.1) for 0.7 mM excess S(IV) at 25 degrees C. The proposed mechanism includes a rapid reaction (k(1) = 3.0 x 10(7) M(-1) s(-1)) between BrO(2)(-) and SO(3)(2-) to form a steady-state intermediate, (O(2)BrSO(3))(3-). General acids assist the removal of an oxide ion from (O(2)BrSO(3))(3-) to form OBrSO(3)(-), which hydrolyzes rapidly to give OBr(-) and SO(4)(2-). Subsequent fast reactions between HOBr/OBr(-) and SO(3)(2-) give Br(-) and SO(4)(2-) as final products. In contrast, the chlorite reactions with S(IV) are 5-6 orders of magnitude slower. These reactions are specific-acid, not general-acid, catalyzed. In the proposed mechanism, ClO(2)(-) and SO(3)H(-)/SO(2) react to form (OClOSO(3)H)(2)(-) and (OClOSO(2))(-) intermediates which decompose to form OCl(-) and SO(4)(2-). Subsequent fast reactions between HOCl/OCl(-) and S(IV) give Cl- and SO(4)(2-) as final products. SO(2) is 6 orders of magnitude more reactive than SO(3)H-, where k(5)(SO(2)/ClO(2)(-)) = 6.26 x 10(6) M(-1) s(-1) and k(6)(SO(3)H(-)/ClO(2)(-)) = 5.5 M(-1) s(-1). Direct reaction between ClO(2)(-) and SO(3)(2-) is not observed. The presence or absence of general-acid catalysis leads to the proposal of different connectivities for the initial reactive intermediates, where a Br-S bond forms with BrO(2)(-) and SO(3)(2-), while an O-S bond forms with ClO(2)(-) and SO(3)H-.     

Preparation of 3-methyl-4-vinyl-1,2,5-oxadiazole and 3-methyl-4-vinyl-1,2,5-thiadiazole

Short and high yielding preparations of 3-Methyl-4-vinyl-1,2,5-oxadiazole ( 6a ) and 3-Methyl-4-vinyl-1,2,5-thiadiazole ( 6b ) are described.     

THE MICROVASCULAR EFFECTS OF PHOTODYNAMIC THERAPY: EVIDENCE FOR A POSSIBLE ROLE OF CYCLOOXYGENASE PRODUCTS

Photodynamic therapy (PDT) of malignant tumours may involve the interruption of tumor and peritumor microcirculation. We have studied the effect of light activation of the photosensitizing drug dihematoporphyrin ether (DHE) on rat subcutaneous arterioles and the modulation of these effects by cyclooxygenase inhibitors indomethacin and acetyl salicylic acid (ASA). Animals received DHE 48 h prior to light activation and additionally either indomethacin, ASA or saline 3 h prior to treatment. Light activation (630 nm, 60 J/cm2) resulted in a significant reduction to 62 +/- 2% SEM of initial blood flow. This effect was inhibited by ASA (98 +/- 8% SEM) and indomethacin (87 +/- 8% SEM). Results from the administration of various doses of both compounds indicate that this inhibition is dose related. The data presented here show that PDT causes a significant reduction in blood flow in normal arterioles and that this effect was inhibited by ASA and indomethacin indicating that prostaglandins or thromboxane A2 may play an important role in the microvascular response to PDT.