ChemInformVolume 21, Issue 3 Reviews ChemInform Abstract: Chiroptical Properties and Absolute Configurations of Chiral Quinones H. E. SMITH, H. E. SMITH Edited by Patai, S. ;Rappoport, Z. ;Wiley, Chichester, UKSearch for more papers by this author H. E. SMITH, H. E. SMITH Edited by Patai, S. ;Rappoport, Z. ;Wiley, Chichester, UKSearch for more papers by this author First published: January 16, 1990 https://doi.org/10.1002/chin.199003331Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue3January 16, 1990 RelatedInformation

AbstractIntroductionAsymmetric SynthesisEstimation of Enantiomeric ExcessElectronic Circular Dichroism (ECD)Vibrational Optical Activity (VOA)

The accuracy of Secondary Ion Mass Spectrometry (SIMS) depth profiles of aluminum (Al) dopant in silicon carbide (SiC) has been investigated. The Al SIMS profile differs in shape depending on whether it was obtained using a cesium (Cs+) or oxygen (O-2(+)) primary ion beam, and depends in the former case on which secondary ion is followed. The matrix signals indicate that the CsAl+ secondary ion yield changes during the Cs+ depth profile, probably because of the work function lowering due to the previously-implanted Al. These same matrix ion signals are used for a depth-dependent empirical correction to increase the accuracy of the Al concentration profile. The physics of these phenomena and the accuracy of the correction are discussed.

A multiple data point version of the industry standard, two data point raster-changing procedure is employed to measure low levels (< 1 x 1017 atoms/cm3) of nitrogen (N) in silicon carbide (SiC) by SIMS (Secondary Ion Mass Spectrometry). A current-changing procedure is also employed. Together, these are used evaluate the assumptions of the standard method, to separate and measure the components of background signal, and to improve upon the precision and accuracy of the standard method. The risk of poor precision in the two-point method is demonstrated, as is the improvement provided by the multiple-point method. Results show that, in addition to the wellknown N memory background, adsorption background can contribute significantly to the N signal. In general, establishing the presence of adsorption gas in this way can be used to warn of the presence of ionization background, which is not measurable per se.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The sign of the 1Lb Cotton effects (CEs) of the benzene chromophore from about 240 to 270 nm in the circular dichroism (CD) of enantiomers of ring-substituted chiral benzylcarbinamines and benzylcarbinamine salts are correlated with their absolute configurations using the benzene sector rule and a consideration of the equilibrium between their two conformers of lowest energy and of oppositely signed rotatory power. These CEs are the result of vibronic borrowing from allowed transitions of the benzene chromophore at shorter wavelength, but an induced rotatory contribution, the sign of which may be predicted using the benzene chirality rule, is small compared to the vibronic contribution and need not be considered when predicting the sign of the 1Lb CEs.

ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTStereochemistry of Radical Reactions: Concepts, Guidelines, and Synthetic Applications By Dennis P. Curran (University of Pittsburgh), Ned A. Porter (Duke University), and Bernd Giese (University of Basel). VCH: New York. 1995. xii + 280 pp. $95.00. ISBN 3-527-29372-8.Howard E. SmithView Author Information Vanderbilt UniversityCite this: J. Am. Chem. Soc. 1996, 118, 51, 13117–13118Publication Date (Web):December 25, 1996Publication History Published online25 December 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja965592thttps://doi.org/10.1021/ja965592tbook-reviewACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views367Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Addition reactions,Cyclization,Hydrocarbons,Molecular structure,Organic reactions Get e-Alerts

The sign of the (1)L(b) Cotton effects (CEs) from about 240 to 270 nm in the circular dichroism (CD) of enantiomers of chiral benzylcarbinamines and benzylcarbinols is correlated with their absolute configurations using the benzene sector rule and a consideration of the equilibrium between their two conformers of lowest energy and of oppositely signed rotatory powers. For chiral benzylalkylcarbinamines, carbinamine salts, and carbinols, which show a single sign for their (1)L(b) CEs, a Shift in the conformational equilibrium can explain a sign reversal of the CEs with a change in solvent, (R)-2-amino-1-phenylpropane showing negative (1)L(b) CEs in methanol but positive ones in cyclohexane. L-Phenylalanine in water shows positive (1)L(b) CEs, but in methanol it shows both negative and positive CD maxima. In methanol, the two longest wavelength maxima comprise a double CE associated with the band origin absorption maximum at 267 nm, the conformational equilibrium shifted from the positive conformer of L-phenylalanine to its negative one and the greater amount of the latter is now detected at slightly longer wavelength in the CD spectrum.

The mechanism by which the hormones 5 alpha-dihydrotestosterone and testosterone differentially regulate such diverse functions as development of male internal and external genitalia and maintenance of prostatic growth via a single androgen receptor (AR) is not well understood. To search for potential AR isoforms, an extensive pharmacological survey of the binding of [3H]mibolerone (7 alpha,17 alpha-[3H]dimethyl-19-nortestosterone) in dog prostate, adrenal gland, testis, liver, kidney, brain, muscle, and spleen cytosolic extracts was carried out. The antagonist androst-4-en-3,17-dione (ATD), as well as a series of unsaturated analogues of testosterone, exhibited marked tissue specificity for binding to mibolerone-binding proteins (MBPs), with ATD having a 10-fold higher affinity for the MBPs present in liver than for those in prostate and testis. The difference in affinity was not due to tissue-specific metabolism of ATD. Competition binding profiles for ATD with mixtures of prostate and liver extracts were consistent with two distinct populations of binding sites. Both wild-type human AR-B and the recently discovered human AR-A isoform were expressed in COS cells and were found to exhibit pharmacology similar to that of the prostatic MBPs in dogs. Analogues of ATD or testosterone could prove to be useful probes for delineating the differential effects of 5 alpha-dihydrotestosterone and testosterone on the biological actions of the AR and related proteins.

Series of 5,11-dicarbo- and 11-carbo-5-oxy-10-(1-alkyl-1,2,3,6-tetrahydro-4 pyridinyl) analogues and a 11-carbo-5-oxy-10-(1-methyl-4-piperidinyl) analogue of the atypical antipsychotic agent clozapine were prepared and tested for binding to the dopamine D-2L and D-4 and serotonin S-2A and S-2C receptors. Some of these analogues were found to have dopamine D-2L and D-4 and serotonin S-2A and S-2C receptor binding activities as high as or higher than those of clozapine, indicating that neither the diazepine structure nor the piperazine ring present in clozapine is essential for high antidopamine activity and or for high dopamine D-4 selectivity (Ki for the dopamine D-2L receptor/Ki for the dopamine D-4 receptor). Increasing in the effective size of the alkyl substituent at the tertiary amine nitrogen atom in the 1,2,3,6-tetrahydro-4-pyridinyl moiety in the 5H-dibenzo[a,d]cycloheptene series reduces the affinity for the dopamine D-4 receptor, but in the dibenz[b,f]oxepin series, no significant change in binding affinity to the dopamine D-4 receptor was observed. Equal or slightly higher affinity for the serotonin S-2A and S-2C receptors was observed for the 10-(1-ethyl-1,2,3,6-tetrahydro-4- pyridinyl) analogues in both series, but for the 10-[1,2,3,6-tetrahydro-1-(2-propenyl)-4- pyridinyl] analogues, any favourable steric factor is overshadowed by an unfavorable electronic effect as a result of change in the basicity of the tertiary amino group in the pyridinyl moiety. Replacement of three of the four nitrogen atoms in clozapine with three carbon or two carbon atoms and an oxygen atom and removal of the chlorine atoms gives 10-(1,2,3,6-tetrahydro-1- methyl-4-pyridinyl)dibenzo[a,d]cycloheptene and 10-(1-methyl-4-piperidinyl)dibenz[b,f]oxepin, each having twice the binding activity to the dopamine D-4 receptor as does clozapine and a dopamine D-4 selectivity equal to that of clozapine.

Androgen-binding protein (ABP) in rat epididymal cytosol and sex hormone-binding globulin (SHBG) in rabbit serum and SHBG purified from human serum were active-site-directed photoaffinity radiolabeled with 17α-[(E)-2-[125I]iodoethenyl]androstan-4,6-dien-17β-ol-3-one ([125I]1). The interaction of this compound with binding components in epididymal cytosol was dependent on exposure of the mixture to ultraviolet light and on the duration of exposure. Photolysis in the presence of [125I]1 and 5α-dihydrotesosterone (5α-DHT) resulted in a 40% inhibition of binding of [125I]1 to cytosolic components. These result indicate that, while [125I]1 interacted with 5α-DHT binding sites, it also formed adducts with other sites. To characterize the labeled species, the photolysis mixture was subjected to electrophoresis under denaturing and reducing conditions. Autoradiography of the gel revealed that ABP and SHBG were labeled with [125I]1, but in cytosol and serum, higher and lower molecular weight components were also labeled. Purified SHBG was labeled, but no labeled contaminating protein was detected. The presence of 5α-DHT completely inhibited [125I]1 photolabeling of human and rabbit SHBG and of ABP. However, in cytosol, the presence of 5α-DHT also eliminated photolabeling to a component that may be albumin, but 5α-DHT did not affect [125I]1 photolabeling of other contaminating proteins in cytosol. Thus, while [125I]1 is an effective photoaffinity radiolabel for ABP and SHBG, the observation that it also photolabels other proteins limits its practical use to the radiolabeling of purified ABP and SHBG preparations.

5H-Dibenzo[b,e][1,4]diazepine, dibenz[b,f]oxepin, and 5H-dibenzo[a,d]cycloheptene analogues of clozapine [8-chloro-11-(4-methylpiperazino)-5H- dibenzo[b,e][1,4]diazepine] were evaluated for their binding affinity to dopamine D-1, D-2, and D-4 and serotonin S-2A (5-HT2A), S-2C (5-HT2C), and S-3 (5-HT3) receptors. The diazepine analogues display selective binding to the dopamine D-4 and serotonin S-2A receptors similar to that of clozapine, but none has a dopamine D-4 selectivity (K-i for the dopamine D-2A receptor/K-i for the dopamine D-4 receptor) greater than that of clozapine. All of the oxepin analogues also show substantial binding to the dopamine D-4 and serotonin S-2A receptors with 10-(4-methylpiperazino)dibenz[b,f]oxepin having a dopamine D-4 selectivity greater than that of clozapine. Some of the 5H-dibenzo-[a,d]cycloheptene analogues also show strong binding to both the dopamine D-4 and serotonin S-2A receptors, 5-methyl-10-(4-methylpiperazino)-5H-dibenzo[a,d]cycloheptene having a dopamine D-4 selectivity of 7.8 as compared to, 10 for clozapine but a serotonin S-2A selectivity (K-i for the dopamine D-2 receptor/K-i for the serotonin S-2A receptor) of 2.0 as compared to 28 for clozapine. The serotonin S-2A selectivity of 2-chloro-10-(4-methypiperazino)-5H-dibenzo[a,d]-cycloheptene is 200. As an extension of these studies, chiral 5-substituted 10-(1,2,3,6-tetrahydro- 1-methyl-4-pyridinyl)-SH-dibenzo[a,d]cycloheptene analogues show a substantial enantiospecificity toward dopamine and serotonin receptor subtypes, (R)-(-)-5-methyl compound having a 2-fold higher dopamine D-4 selectivity than its (S)-(+) enantiomer as the result of enhanced binding to the dopamine D-4 receptor rather than diminished binding to the dopamine D-2 receptor. (pR(a),pS(b))-(+)-5-(2-Propylidene)-10-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-5H-dibenzo[a,d]cycloheptene is 17 times more active in binding to the dopamine D-4 receptor than is its pS(a),pR(b) enantiomer while being only 1.5 times more active in binding to the dopamine D-2 receptor.

Experimental vibrational circular dichroism (VCD) spectra for the dextrorotatory enantiomer and theoretical VCD spectra obtained with localized molecular orbital theory using 6-31G* basis set for the (R) configuration of 2-methylthiirane-3,3-d2 in the 700-1500 cm-1 region are presented. The observed and predicted VCD signs are in very good agreement suggesting that the dextrorotatory enantiomer has the (R) configuration. This conclusion is also supported by the optical rotational data.

Unsaturated analogues of androst-4-en-17 beta-ol-3-one, each with a 17 alpha-iodoethynyl or 17 alpha-(2-iodoethenyl) substituent, were prepared, and their relative binding affinities (RBAs) for androgen-binding protein (ABP) were compared with those of 5 alpha-androstan-17 beta-ol-3-one, androst-4-en-17 beta-ol-3-one, androsta-4,6-dien-17 beta-ol-3-one, and androsta-1,4,6-trien-17 beta-ol-3-one. These binding studies indicate that the iodine[125I] analogues of 17 alpha-iodoethynyl and 17 alpha-[(E)-2-iodoethenyl] derivatives of androsta-4,6-dien-17 beta-ol-3-one and androsta-1,4,6-trien-17 beta-ol-3-one will have RBAs at least twice as great as that of 5 alpha-androstan-17 beta-ol-3-one. They can be prepared from 17 alpha-ethynylandrosta-4-en-17 beta-ol-3-one, the final synthetic step using N-[125I]iodosuccinimide, and are potential radioiodinated, active site-directed photoaffinity ligands for ABP and testosterone-binding globulin.

Experimental and theoretical vibrational Raman optical activity (VROA) spectra of (2R,3R)-2,3-dimethylthiirane in the 200-1500 cm(-1) region are presented. The level of agreement obtained for the observed and predicted VROA signs suggests that the absolute configurations of chiral molecules can be determined confidently using VROA.

Both enantiomers of trans-2,3-dimethyloxirane-d0, trans-2,3-dimethyloxirane-2-d1, and trans-2,3-dimethyloxirane-2,3-d2 are synthesized. Vibrational circular dichroism (VCD) spectra for these compounds are obtained in the 1600-700-cm-1 region. Ab initio theoretical calculations using the localized molecular orbital method (LMO-VCD) and the vibronic coupling theoretical method (VCT) are also obtained for these molecules. A comparison of the theoretical VCD predictions with the corresponding experimental observations demonstrates that the observed VCD features are satisfactorily reproduced by the theories, indicating that absolute configurations can be confidently determined using vibrational circular dichroism.