Carbon positions

In a united atomforce field the van der Waals centre of the united atom is usually associated v ilh the position of the heavy (i.e. non-hydrogen) atom. Thus, for a united CH3 or CH2 group the vem der Waals centre would be located at the carbon atom. It would be more accurate to associate the van der Waals centre with a position that was offset slightly from the carbon position, in order to reflect the presence of the hydrogen atoms. Toxvaerd has developed such a model that gives superior performance for alkemes than do the simple united atom models, particularly for simulations at high pressures [Toxvaerd 1990]. In... 

Section 17 2 The carbonyl carbon is sp hybridized and it and the atoms attached to It are coplanar Aldehydes and ketones are polar molecules Nucleophiles attack C=0 at carbon (positively polarized) and electrophiles especially protons attack oxygen (negatively polarized)... 

As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. 

Nucleophilic Addition. Nucleophilic reagents attack the -carbon position in the conjugated maleic and fumaric frameworks. Basic reaction conditions favor these condensations for the addition of glycolate (21) to maleate [142-44-9] (22) ... 

Antimony Trioxide. Antimony(III) oxide (antimony sesquioxide) [1309-64-4] Sb203, is dimorphic, existing in an orthorhombic modification valentinite [1317-98-2] is colorless (sp gr 5.67) and exists in a cubic form and senarmontite [12412-52-17, Sb O, is also colorless (sp gr 5.2). The cubic modification is stable at temperatures below 570°C and consists of discrete Sb O molecules. The molecule is similar to that of P40 and As O and consists of a bowed tetrahedron having antimony atoms at each corner united by oxygen atoms lying in front of the edges. This solid crystallizes in a diamond lattice with an Sb O molecule at each carbon position. 

Reactions with strongly basic nucleophiles such as potassium amide in liquid ammonia may prove much more complex than direct substitution. 2-Chloro-4,6,7-triphenylpteridine reacts under these conditions via an S ANRORC mechanism to form 2-amino-4,6,7-triphenylpteridine and the dechlorinated analogue (78TL2021). The attack of the nucleophile exclusively at C-4 is thereby in good accord with the general observation that the presence of a chloro substituent on a carbon position adjacent to a ring nitrogen activates the position meta to the chlorine atom for amide attack. 

An ipso attack on the fluorine carbon position of 4-fIuorophenol at -40 °C affords 4-fluoro-4-nitrocyclohexa-2 5-dienone in addtion to 2-nitrophenol The cyclodienone slowly isomenzes to the 2-nitrophenol Although ipso nitration on 4-fluorophenyl acetate furnishes the same cyclodienone the major by-product is 4 fluoro-2,6-dinitrophenol [25] Under similar conditions, 4-fluoroanisole pnmar ily yields the 2-nitro isomer and 6% of the cyclodienone The isolated 2 nitro isomer IS postulated to form by attack of the nitromum ion ipso to the fluorine with concomitant capture of the incipient carbocation by acetic acid Loss of the elements of methyl acetate follows The nitrodienone, being the keto tautomer of the nitrophenol, aromatizes to the isolated product [26] (equation 20) Intramolecular capture of the intermediate carbocation occurs in nitration of 2-(4-fluorophenoxy)-2-methyIpropanoic acid at low temperature to give the spiro products 3 3-di-methyl-8 fluoro 8 nitro-1,4 dioxaspiro[4 5]deca 6,9 dien 2 one and the 10-nitro isomer [2d] (equation 21)... 

Substitution at the vinylcnc carbon position of PPV derivatives reduce their tendency to oxidation. Examples (see Table 13-1) are CN-PPV 12 and DPOP-PPV... 

In the postulated bioluminescence mechanism, firefly luciferin is adenylated in the presence of luciferase, ATP and Mg2+. Luciferyl adenylate in the active site of luciferase is quickly oxygenated at its tertiary carbon (position 4), forming a hydroperoxide intermediate (A). 

Fluoride ion catalyzed reaction of the cyclic nitronate 1 with benzaldehyde provides a cyclic hcmiaeetal 2 in 95% diastereoselectivity18 with tra ,v,tr u.v-relationship of the protons in positions 2, 3 and 4. The relative configuration of the hemiacetal carbon position was not assigned. Upon reaction of the diastereomeric nitronate 3 at 25 °C the 4a-stereocenter is epimerized by fluoride ion such that hemiacetal 2 is once again obtained. In contrast, reaction of 3 at 0°C furnishes the diastereomeric product 4 in 23% yield 8. 

The shifts at the para carbon position for substituted benzenes (and for fris-p-substituted triphenylmethanols) also support the scale as shown by the fitting results of sets 26 (and 27). 

Uniformly labeled 2,4-dichlorophenol- C (purchased from New England Nuclear Corp, Boston, Mass.) was used in the tracer preparation. This provided a label at all carbon positions in the dibenzo-dioxin structure. 2,7-Dichlorodibenzo-p-dioxin- C after initial cleanup by fractional sublimation, contained approximately 5% of an impurity, detected by thin layer chromatography (TLC) which gave mass peaks at 288, 290, 292, and 294 in the mass spectrometer, consistent with a trichloro-hydroxydiphenyl oxide. This is probably the initial condensation product of the Ullman reaction and is most likely 2-(2,4-dichlorophenoxy)-4-chlorophenol. It was removed easily by extractions with aqueous... 

Examination of the multipole populations gives no indication of the discrepancy observed in the model maps, all populations from parallel refinements agreeing to within two esd s (Table 5). The one striking exception is the monopole population (P,) for carbon. This must be a simple difference in the partitioning of the charge density between atom centers in the model as there is no discernible difference in the model maps around the carbon position. 

The Use of deuterium has revealed interesting mechanistic details. Over Rh/C, Pt/C, and Pd/C, the butanone resulting from the deuteriumation of methyl vinyl ketone contains substantially more deuterium at position 4 than at 3 (Table 2.7). This can generally be accounted for by the classic mechanism assuming the a-carbon (position 3) remains preferentially attached to the surface while the P-carbon (position 4) undergoes multiple exchange by repeated second-point attachment (Fig. 2.27). However, over Pd/C, even less deuterium... 

The narrow, resolved lines observed in the H-ENDOR spectrum of P-carotene indicated that the methyl protons at the 5 or 5 and the 9 or 9 carbon positions were undergoing rapid rotation. 

These results were somewhat unexpected in view of the possible decrease in the reactivity of 5-methyl-l,4-hexadiene due to methyl substitution at the 5-carbon position. To differentiate the effect of the double bond at the 4-carbon position... 

The reduced reactivity of 5-methy1-1-hexene is consistent with the expected steric effect due to methyl substitution at the 5-carbon position. Apparently, the internal double bond in 5-methyl-l,4-hexadiene assists in its complexation at the active site(s) of the catalyst prior to its polymerization and thereby the "local concentration" of this monomer is higher than the feed concentration during copolymerization with 1-hexene. This view is consistent with the observation that the overall rates of polymerization, under the same conditions, are much lower for the system containing 5-methyl-1,4-hexadiene. 

These data support the expectation that the substitution of a methyl group at the 4-carbon position has a significantly greater effect in reducing the reactivity than does similar substitution at the 5-carbon atom. 

The iodoacetamido derivatives of fluorescein possess a sulfhydryl-reactive iodoacetyl group (Chapter 1, Section 4.2 and Chapter 2, Section 2.1) at either the 5- or 6-carbon position on their lower ring. The isomers are commercially available in purified form, since some reactivity and specificity differences between the 5- and 6-derivatives toward various sulfhydryl sites in proteins may be observed. Both iodoacetamido derivatives are among the most intense fluoro-phores available for labeling biomolecules due to high QY. 

Texas Red hydrazide is a derivative of Texas Red sulfonyl chloride made by reaction with hydrazine (Invitrogen). The result is a sulfonyl hydrazine group on the No. 5 carbon position of the lower-ring structure of sulforhodamine 101. The intense Texas Red fluorophore has a QY that is inherently higher than either the tetramethylrhodamine or Lissamine rhodamine B derivatives of the basic rhodamine molecule. Texas Red s luminescence is shifted maximally into the red region of the spectrum, and its emission peak only minimally overlaps with that of fluorescein. This makes derivatives of this fluorescent probe among the best choices of labels for use in double-staining techniques. 

BODIPY fluorophores are a class of probes based on the fused, multi-ring structure, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (Figure 9.27) (Invitrogen) (U.S. patent 4,774,339). This fundamental molecule can be modified, particularly at its 1, 3, 5, 7, and 8 carbon positions, to produce new fluorophores with different characteristics. The modifications cause spectral shifts in its excitation and emission wavelengths, and can provide sites for chemical coupling to label biomolecules. 

A mixture of exo- and endo-isomers of 5-methylbicylo[2.2.1]hept-2-ene is hydrogenated with the aid of five equivalents of triethylsilane and 13.1 equivalents of trifluoroacetic acid to produce a 45% yield of < <7o-2-methylbicylo[2.2.1] heptane (Eq. 71). The same product is formed in 37% yield after only five minutes. The remainder of the reaction products is a mixture of three isomeric secondary exo-methylbicylo[2.2.1]heptyl trifluoroacetates that remains inert to the reaction conditions. Use of triethylsilane-l-d gives the endo-2-methylbicylo-[2.2.1]heptane product with an exo-deuterium at the tertiary carbon position shared with the methyl group. This result reflects the nature of the internal carbocation rearrangements that precede capture by the silane.230... 

The GIAO-MP2/TZP calculated 13C NMR chemical shifts of the cyclopropylidene substituted dienyl cation 27 show for almost all carbon positions larger deviations from the experimental shifts than the other cations 22-26. The GIAO-MP2/TZP method overestimates the influence of cr-delocalization of the positive charge into the cyclopropane subunit on the chemical shifts. Electron correlation corrections for cyclopropylidenemethyl cations such as 27 and 28 are too large to be adequately described by the GIAO-MP2 perturbation theory method and higher hierarchies of approximations such as coupled cluster models are required to rectify the problem. 

In the case of boron impurities a complementary situation occurs. Boron has only three outer bonding electrons instead of the four found on carbon. Each boron impurity atom occupies a carbon position, forming Be, which results in the creation of a set of new acceptor energy levels just 0.64 x 10 19 J (0.4 eV) above the valence band. The transition of an electron from the valence band to this acceptor level has an absorption peak in the infrared, but the high-energy tail of the absorption band spills into the red at 700 nm. The boron-doped diamonds therefore absorb some red light and leave the gemstone with an overall blue color. 

The alcohol moiety is produced in a different manner from that of the acid moiety. The alcohol moiety resembles the plant hormone jasmonic acid (JA) (26) generated from linolenoyl moiety of lipids via (13,S )-hydroperoxy-linolenic acid (22), (12.13,S )-epoxylinolenic acid (23), and 12-oxo-cis-10.15-phytodienoic acid (24) by the oxylipin or octadecanoid pathway (Fig. 3) [31]. In fact, 13C was incorporated at pyrethrolone (1) carbon positions that agreed with those predicted to be labeled when the alcohol moiety is produced via the pathway (Fig. 3) [30]. Figure 3 illustrates that m-jasmone (25) is hydroxylated to yield jasmololone (4), which is then dehydrogenated to yield pyrethrolone (5). However, it has not yet been determined if this is actually the case. 

In the intervening years, indoleboronic acids substituted at all indole carbon positions have found use in synthesis. For example, Claridge and co-workers employed 94 in a synthesis of isoquinoline 95 under standard Suzuki conditions in high yield [114], Compound 95 was subsequently converted to the new Pd-ligand l-methyl-2-diphenylphosphino-3-(l -iso-quinolyl)indole. 

Experiments by Kenyon and Blois, with samples of phenylalanine labelled with i4C at each of the three aliphatic carbon positions, showed that the molecule could photolyse at each of the three exocyclic carbon-carbon bonds. Decarboxylation was also thought to be an important process, but unfortunately no resulting phenylethylamine was detected during this work. Mechanisms for the production of the observed products were suggested [24],... 

The measurements of the labeled metabolites may be performed with GC- or LC-MS, or by NMR. Because it is the most commonly used method, we will only consider GC-MS based approaches here. Obviously and unfortunately, it is not possible to directly measure the isotopomer enrichments by GC-MS, because the apparatus only yields total masses of molecules or fractions thereof, but not directly the position of a label. Each MS peak is produced by all isotopomers with the same molecular weight that is, the same number of labeled carbon positions. Sometimes this concept is also called mass isotopomers [264]. In a so-called retrobiosynthetic approach, it has been shown that the labeling state of many intracellular pools can be determined indirectly by measuring the labels in macromolecular biomass components at steady state for example, the labeling state of alanine from hydrolyzed protein reflects the label of pyruvate [265]. Using this approach, it is possible to quantify fluxes into storage components. 

FlC. 64. The tightly associated domains (one shown light and the other dark) of elastase. Figures 64 through 66 use a space-filling representation with a sphere around each a-carbon position they were photographed from Richard Feldmann s molecular graphics display at the National Institutes of Health. 

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