Charles L. Watkins

Synthesis, separation and characterization of the mono- and diazide analogs of ethidium bromide

Ethidium bromide is used to characterize nucleic acid secondary and tertiary structural properties and the biological consequences of drug interactions. The mono- and diazido analogs of ethidium have proven valuable as photoaffinity probes in chemical and biological studies on nucleic acids, since they render the ethidium-nucleic acid interaction covalent. Although both of these compounds have been synthesized previously, the published synthesis procedure for the monoazide is inadeqlate since a major portion of the product has been identified as the diazide analog. This lack of purity severely limits the usefulness for nucleic acid research. The procedure presented here for the synthesis, separation, purification and crystallization of these analogs should provide the quantities and quality of these important reagents needed to perform a variety of chemical and biological experiments.

Synthesis, reactions and X-ray crystal structures of metallacrown ethers with unsymmetrical bis(phosphinite) and bis(phosphite) ligands derived from 2-hydroxy-2′-(1,4-bisoxo-6-hexanol)-1,1′-biphenyl

Abstract Chlorodiphenylphosphine and 2,2′-biphenylylenephosphorochloridite react with 2-hydroxy-2′-(1,4-bisoxo-6-hexanol)-1,1′-biphenyl to yield the new α,ω-bis(phosphorus-donor)-polyether ligands, 2-Ph 2 PO(CH 2 CH 2 O) 2 –C 12 H 8 -2′-OPPh 2 ( 1 ) and 2-(2,2′-O 2 C 12 H 8 )P(CH 2 CH 2 O) 2 –C 12 H 8 -2′-P(2,2′-O 2 C 12 H 8 ) ( 2 ). These ligands react with Mo(CO) 4 (nbd) to form the monomeric metallacrown ethers, cis -Mo(CO) 4 {2-Ph 2 PO(CH 2 CH 2 O) 2 –C 12 H 8 -2′-OPPh 2 } ( cis - 3 ) and cis -Mo(CO) 4 {2-(2,2′-O 2 C 12 H 8 )P(CH 2 CH 2 O) 2 –C 12 H 8 -2′-P(2,2′-O 2 C 12 H 8 )} ( cis - 4 ), in good yields. The X-ray crystal structures of cis - 3 and cis - 4 are significantly different, especially in the conformation of the metal center and the adjacent ethylene group. The very different 13 C-NMR coordination chemical shifts of this ethylene group in cis - 3 and cis - 4 suggest that the solution conformations of these metallacrown ethers are also quite different. Both metallacrown ethers undergo cis – trans isomerization in the presence of HgCl 2 . Although the cis – trans equilibrium constants for the isomerization reactions are nearly identical, the isomerization of cis - 3 is more rapid. Phenyl lithium reacts with cis - 3 to form the corresponding benzoyl complexes but does not react with either trans - 3 or cis - 4 . Both the slower rate of cis – trans isomerization of cis - 4 and its lack of reaction with PhLi are consistent with weaker interactions between the hard metal cations and the carbonyl oxygens in both trans - 3 and cis - 4 .

Reactions of As(NMe2)3 and Sb(NMe2)3 with aluminum and magnesium alkylating agents

Abstract The reactions of aluminum alkyls, R 3 Al (R  Me, Et, Pr n , Bu n and Bu i , with As(NMe 2 3 and Sb(NMe 2 ) 3 have been used to synthesize the respective tertiary arsines, R 3 As, and tertiary stibines, R 3 Sb, in good yields. As(NMe 2 ) 3 also reacts with Grignard reagents RMgX (R  Et, Pr n , Pr i , Bu n , Bu i , Bu t , Ch 2 CH, CH 3 CHCH, Me 3 SiCH 2 , Ph, p -tolyl and mesityl), to give R 3 As. Complete 13 C and 1 H NMR spectral data on the synthesized R 3 Sb and [R 2 AlNMe 2 ] 2 are also reported.

Synthesis and characterization of Me3Ga and Me3In: Adducts of secondary amines

Abstract The reactions of trimethylgallium and trimethylindium with a variety of secondary amines [HNMe 2 , HNEt 2 , HNPr 2 n , HNPr 2 i , HNBu 2 i , HNBu 2 s , HN(CH 2 Ph) 2 , HN( c -C 6 H 11 ) 2 , HNC 4 H 8 , HNC 5 H 10 , HNC 6 H 12 and HN(CH 2 CH 2 ) 2 NMe], produce a series of room-temperature stable liquid or solid adducts. These were characterized by 1 H and 13 C NMR, IR, mass spectrometry and elemental analysis. Spectroscopic comparisons are made between these and the corresponding trimethylaluminum derivatives. 1 H and 13 C NMR data for all three series of adducts indicate a correlation between the chemical shifts of the methyl groups on the metal and the relative steric requirements of the amines. The data show a general downfield movement of these chemical shifts with increasing steric bulk.

The chemical dynamics of 1,4,8,11-tetraazacyclotetradecane nickel(II) perchlorate with several solvents. I. Thermodynamics of base adduct formation

Abstract A solvent adduct study of 1,4,8,11-tetraazacyclotetradecane nickel(II) perchlorate with the coordinating solvents acetonitrile, N,N-dimethylformamide (DMF), methyl sulfoxide (DMSO), and water by optical and nmr techniques is reported. The thermodynamic parameters ΔH°, ΔS°, and K eq for adduct formation are given for each solvent system. At 25 °C, the stability order is found to be DMF > CH 3 CN > DMSO > H 2 O. A comparison of the observed stability order and stabilities predicted by single optical measurements and solvent donicity is presented.

Reactivity of (Me3Al)2 with selected aminoarsines and secondary amines

Abstract The reactions of (Me3Al)2 with 11 aminoarsines, Me2AsR (R = Et2N, Prn2N, Pri2N, Bun2N, Bui2N, C4H8N, C5H10N, C6H12N, CH3NC4H8N, Ph2N and Bzl2N, where Bzl = PhCH2), have been studied by multinuclear NMR spectroscopy. The results are compared with those of our previous studies on the Me3Al/Me2AsNMe2 system. In each case, except Me2AsNPh2, the final reaction products are [Me2AlR]2 and Me3As. The reaction intermediates have been identified and, in most cases, the AsNAl adducts and Me2AlR·AlMe3 are observed. With Me2AsNPh2 the product is Me3As·Me2AlNPh2. The influence of steric and electronic effects on arsenic vs nitrogen bonding site preference, adduct stability, complexity of overall reaction and ease of forming Me3As and [Me2AlR]2 are discussed. [Me2AlR]2, Me2AlR·AlMe3 and Me3Al·HR have been independently synthesized and characterized. A comparison of the 13C NMR chemical shift values for Me2AsR and Me2AsR·AlMe3 provides information on steric interactions that influence adduct stability.

Multinuclear NMR studies of the reactions of MeAsH2 with Me2AsNMe2 and Me2AsNMe2·BH3

Abstract The reactions of MeAsH2 with Me2AsNMe2 and Me2As NMe 2 ·B H3 have been carried out in toluene-d8 solution as a function of temperature and time. The progress of the reactions was monitored by multi- nuclear (1H, 11H, and 13C) NMR spectroscopy over the temperature range of −80 and −10 °C. NMR spectral data analysis suggests the initial formation of an unstable intermediate, Me2AsAs(H)Me, which undergoes multiple condensation reactions to give (MeAs)5. The other products of the reactions are Me2AsAsMe2, Me2AsH, MeAsH2, Me2NH or Me2NH· BH3 and uncharacterized, condensed, AsAs bonded compounds. Several competitive exchange reactions involving compounds capable of exchanging H-, Me2As-, and Me2N- units influence the rate of reaction, as well as the product yields. The reactions involving , and (Me/As)5/AsH2, systems have been examined to determine their relative significance in the reactions of MeAsH2 with Me2AsNMe2 and its NB bonded BH3 adduct.

Synthesis and characterization of a series of aminogallanes, [Me2GaR]2 The crystal structures of [Me2GaN(CH2Ph)2]2 and [Me2GaN(CH2CH2)2NMe]2

Abstract Me3Ga was allowed to react with a series of ten amines at 110°C in toluene to give 75 to 90% yields of the corresponding aminogallanes, [Me2GaR]2 [R  NMe2, NEt2, NPr2n, NBu2n, NBu2i, N(c-C6H11)2, NC4H8, NC5H10, NC6H12, and N(CH2CH2)2 NMe], via a 1,2-elimination of CH4. Similarly, [Me2AlNBu2s]2 and [Me2AlN(c-C6H11)2]2 were prepared by an analogous thermolysis reaction. On the other hand, synthesis of [Me2GaNPr2i]2, [Me2GaNBu2s]2, and [Me2GaN9CH2Ph2]2 was achieved by the reaction of Me2GaCl with the respective lithium amide. A comparison of the 1H and 13C NMR chemical shifts for the aminogallanes with those previously obtained for the analogous series of aminoalanes indicates a similar sensitivity to the influence of the amide moiety. X-ray crystal structures were determined for [Me2GaN(CH2Ph)2]2, which has a slightly puckered four-membered Ga2N2 core, and [Me2GaN(CH2CH2)2NMe]2, which has a planar four-membered Ga2N2 core.

Chemical esterification of 5'-AMP occurs predominantly at the 2' position.

SummaryWe describe experiments here which show that chemical esterification of 5′-adenylic acid (5′-AMP) withN-acetylD-orL-phenylalanine (Ac-D- or Ac-L-Phe) imidazolide occurs principally, if not exclusively, at the 2′ position. Furthermore, in experiments with the formation of the 2′–3′ diester with butyric acid andN-acetyl glycine (Ac-Gly), we found the second esterification was also predominantly at the 2′ position. This means that mixed diesters can be predictably prepared with the positions of the substituents known. The results are consistent with a model for the preferential catalytic synthesis ofL-based peptides via a 2′–3′ diester intermediate of purine monoribonucleotides.

Multinuclear NMR studies of the reactions of (Me3Al)2 with Me2AsNMe2, MeAs(NMe2)2 and As(NMe2)3

Abstract The reactions of (Me 3 Al) 2 with Me 2 AsNMe 2 , MeAs(NMe 2 ) 2 and As(NMe 2 ) 3 were studied as a function of time at room temperature and over the temperature range of −95 to 24°C by using 1 H and 13 C NMR spectroscopy. At −95°C, all the aminoarsines form the respective mono AlN bonded adducts. In addition, MeAs(NMe 2 ) 2 and As(NMe 2 ) 3 form bis AlN bonded adducts and As(NMe 2 ) 3 forms an AlAs bonded adduct. The bis adducts readily decompose and the AlAs bonded adduct dissociates at low temperature. All the mono AlN bonded adducts decompose by a pathway that transfers a methyl group from the aluminium to the arsenic atom, cleaves the AsN bond, and yields the next higher methyl homologue in the arsine series [MeAs(NMe 2 ) 2 ,Me 2 AsNMe 2 or Me 3 As]. The bis AlN bonded adducts decompose to the next higher methyl homologue in the mono adduct series [MeAs(NMe 2 )NMe 2 ·AlMe 3 or Me 2 AsNMe 2 ·AlMe 3 ]. The other product in both cases is the unstable Me 2 AlNMe 2 , which dimerizes or undergoes further reaction with excess (Me 3 Al) 2 or aminoarsine. The role of numerous competing side reactions and adduct/aminoarsine exchange equilibria in affecting the rate of adduct decomposition, overall rate of formation of the final product arsine, and final product distribution was established for each aminoarsine/(Me 3 Al) 2 system. The initial stoichiometry of the reaction greatly influences the relative importance of the various reactions that occur in solution. Only when the moles of available Me 3 Al molecules equal those of Lewis base nitrogen sites, do the reactions proceed in a straightforward manner to give Me 3 As and (Me 2 AlNMe 2 ) 2 . The results from the NMR studies were used to design a new, high yield synthetic route to Me 3 As.