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This paper summarizes the design considerations and developmental status of a wideband holographic system breadboard designed to prove the feasibility of recording and reproducing digital data at 400 Mbits/sec and 40 Mbits/sec, respectively. The following critical system elements were investigated: multiplexer–demultiplexer electronics, linear data composer, polygonal mirror scanner, holographic recording techniques, and data readout devices. The feasibility of recording digital data in multichannel holographic form at high densities has been demonstrated on a subsystem basis.

Various new metalloporphyrins, including both Fe(II) and Fe(III), Co(II), and Co(III) complexes of p-substituted-tetraphenylporphines, were synthesized for use as possible model compounds in the study of the mechanisms of the oxidation-reduction of the heme-enzymes and cobalamines. Characteristic differences were observed in the near-ultraviolet, visible, and infrared spectra of the complexes of different metal ions. These compounds may also be of interest as specific radiation sensitizing or protecting agents.

The molecular structure of 5-[1-(2′-deoxy-α-d-ribofuranosyl) uracilyl] disulfide (I) has been determined by X-ray crystallographic analysis. The molecule crystallizes in the orthorhombic space group P212121, with the following cell dimensions: a= 9.492 Å., b= 14.061 Å., c= 16.328 Å. The valence state about the S-S linkage appears to be markedly different from that observed in other disulfide structures. The torsional angle about this bond is 49° and the S-S bond length was found to be 2.108 å. The configurations of both the uracil and the deoxyribosyl residues are different in the two nucleoside units of the molecule. The crystal is bound together by hydrogen bonds.

Procedures were developed for the quantitative estimation of 2,2-dimethylaziridine containing alkylating agents in blood and urine. Rapid alkalinization of the biological samples, followed by protein precipitation and extraction of the compounds at high salt concentration into acetophenone, resulted in good recoveries. The use of a nonaqueous solvent (acetophenone) and the adoption of N-phenylpiperazine as the proton-accepting reagent significantly improved the sensitivity and reproducibility of the colorimetric assay with 4-(p-nitrobenzyl)pyridine. These improvements appear to be generally applicable to the quantitative determination of aziridine-type alkylating agents. The 2,2-dimethylaziridine agents were shown to undergo extremely rapid hydrolysis under neutral or acidic conditions and were stable only in alkaline solution. The half-lives of tris(2,2-dimethyl-1-aziridinyl)phosphine oxide, bis(2,2-dimethylaziridinyl)phosphinylurethan, and ethyl bis(2,2-dimethyl-1-aziridinyl)phosphinate in whole blood, at 37°, pH 7.38, were 7, 11, and 18 min., respectively; the corresponding half-lives in plasma were approximately four times longer.

The syntheses of a series of ring-substituted ethyl [bis(1-aziridinyl)phosphinyl]-carbamates are reported. Several of these compounds showed significant tumor inhibitory activities in experimental animals, and one of them, ethyl [bis(2,2-dimethyl-1-aziridinyl)phosphinyl]carbamate (AB-132), is currently under clinical investigation as an experimental antineoplastic agent.

ALKYLATING agents have been used in the Ltreatment of neoplastic disease since 1931, when Adair and Bagg1 described experiences with topical application of sulfur mustard. Intensive investigation during World War II resulted in a greater appreciation of the usefulness of these compounds. Pharmacological studies of mechlorethamine (methyl-bis [β-chloroethyl] amine) hydrochloride have been conducted almost entirely with biological tests, relying upon the lethality of the agent in the experimental animal to indicate potency.Recently, a colorimetric chemical determination has been developed2 by which it is possible to quantitate the presence of alkylating agents in aqueous biological media. With this test, many aspects of the basic reactions of mechlorethamine have been studied in order to confirm or repudiate concepts established by less accurate techniques.To gain knowledge as to the final applicability of the alkylating agent test and to determine its potential importance regarding the testing of new alkylating substances

Methylation of 2,4-diamino-6,7-dimethylbenzo(g)pteridine (I) with excess methyl iodide in boiling cellosolve gave a red methyl-methiodide derivative (II) which, on treatment with hot aqueous sodium carbonate solution was converted to the N1-methyl derivative (III), as shown by hydrolysis of the product to the corresponding dioxo-compound (IV) and its further degradation to the quinoxaline derivative (V). Reaction of I with methyl iodide in nitromethane solution afforded a quaternary methiodide derivative (VI) which, through a series of reactions with cold, concentrated acid and base reagents, was converted to III. On several occasions, the latter was obtained in what appeared to be a different, unstable tautomeric form. Hydrolysis of the corresponding intermediate methiodide (VI) or, of the hydrochloride salt (VII), with acid or alkali, gave IV; thus the methylation of I in nitromethane, as in cellosolve, appears to have occurred exclusively in the N1-position of the pyrimidine ring.

5-Mercaptouracil (1) and 5-mercaptodeoxyuridine (II), structural analogs of thymine and thymidine, respectively, are effective growth inhibitors in various biological systems and under study as potential antineoplastic and antiviral agents. Both compounds were found to be extremely unstable in aqueous solutions as they undergo rapid autoxidation to the corresponding disulfides. Determination of the ultraviolet spectra and pKa values of the thiols was possible only by special techniques, using dithiothreitol (DTT) as a “protecting” agent. Both I and II have very low pKa's, and their anionic forms show characteristic absorption maxima in the 330-mμ region. These results are discussed in comparison with the spectra and ionization equilibria of related compounds including some new S-substituted derivatives of I and II. DTT was found to be also a uniquely suitable reagent for the preparation of pure I and II by stoichiornetric reduction of the corresponding disulhdes. A special technique was developed for the quantitative determination of the free thiols.

Bis(trans-2,3-dimethylaziridinyl)phosphinyl urethan (IV) was synthesized and compared with the corresponding cis-2,3-dimethyl derivative (III). The comparative alkylating activities and rates of hydrolysis of these two stereoisomeric aziridine derivatives, III and IV, were determined and compared with corresponding data for the monomethyl derivative (V) and two other clinically tested members of this series of antineoplastic agents (dual antagonists), AB-100 (I) and AB-132 (II). The structures of the final hydrolysis products of III, IV, and V were determined and confirmed by direct synthesis. The results indicate that the mechanisms of hydrolysis of III, IV, and V (as that of the unsubstituted aziridine derivative, AB-100) are essentially SN2, in contrast to the much faster hydrolysis of the 2,2-dimethylaziridine analog, AB-132, which involves a carbonium-ion mechanism. These studies give further support to the hypothesis that the unique pharmacologic properties of AB-132, as compared to other members of this series, may be related to the unique chemical properties of the 2,2-dimethyl-aziridine moieties.

The title compound, a new analog of the experimental anticancer agent, AB-132, was synthesized and tested against a spectrum of transplanted animal tumors. It was found to have significant chemotherapeutic activity in all of the tumor systems studied. In these assays, the new compound was a much more effective antitumor agent than AB-132.

5-MERCAPTOURACIL, a structural analogue of thymine, was synthesized several years ago1,2. This compound (and its disulphide) inhibited the growth of Lactobacillus leichmannii at 1–3 µgm./ml. concentration, and this inhibition could be reversed ‘competitively’ with thymine. It was tested in several experimental mouse tumours; in some cases, it caused tumour inhibition of borderline significance, at less than the maximum tolerated dose3.

THE concept of combination chemotherapy in the treatment of neoplastic diseases has been receiving considerable attention during the past few years. Some see the only theoretically possible solution to the problem of cancer chemotherapy in the simultaneous use of several synergistic drugs blocking several consecutive and/or alternative metabolic pathways, while others vigorously object to this thesis, from practical considerations or disappointing experiences.

THE R-phase was first found1in the chromium–molybdenum–cobalt ternary system. Its crystal structure has been determined by Shoemaker et al.2. Additional R-phases were later found in the molybdenum–manganese–cobalt and molybdenum–manganese–iron ternary systems3, as well as in the titanium–manganese binary system4. Recently, in the investigation of several ternary systems with silicon a number of new R-phases have been identified. Table 1 gives the approximate composition and the lattice parameters of these new R-phases: