A new method for the assessment of the π-acceptor strength of N-heterocyclic carbenes is presented. The 77Se chemical shifts of the easily available selenium carbene adducts 1·Se–7·Se correlate with the π-acceptor character of the respective carbenes. The observed δ(77Se) values cover a range of almost 800 ppm, with increasing π-acidity leading to a downfield shift of the signal.

Key indicatorsSingle-crystal X-ray study T = 293 K Mean (C-C) = 0.003 Å R factor = 0.035 wR factor = 0.100 Data-to-parameter ratio = 10.9For details of how these key indicators were automatically derived from the article, see

parallel orientation with respect to the plasma membrane. However, after integrating published experimental data on glycan chain length distribution and the degree of peptide side chain cross-linking into this computer simulation, we now report that the proposed planar network of murein appears largely dysfunctional. In contrast, a scaffold model of murein architecture, which assumes that glycan strands extend perpendicularly to the plasma membrane, was found to accommodate published experimental evidence and yield a viable stress-bearing matrix. Moreover, this model is in accordance with the wellestablished principle of murein assembly in vivo, i.e., sequential attachment of strands to the preexisting structure. For the first time, the phenomenon of division plane alternation in dividing bacteria can be reconciled with a computer model of the molecular architecture of murein.The biological role, chemical structure, physical properties, and principles of biogenesis of cell walls of both gram-positive and gram-negative bacteria have been extensively reviewed since the mid-1960s (1, 8, 17-19, 26, 29, 33, 44, 51, 53, 56, 57). The major structural component of all types of bacterial walls is murein, the terms murein and peptidoglycan being synonymous. Although its composition and fine chemical structure vary in different bacteria (52), the general principle of its structural organization holds constant. The material, regardless of the bacterial cell morphology and the wall thickness, is invariably composed of peptidoglycan strands cross-linked via peptide bridges. Other polymers that are associated with the sacculus in different bacteria (teichoic acids, lipoteichoic acids, polysaccharides, proteins, and lipoproteins) are not essential to the mechanical firmness of murein and, therefore, are not further discussed here.To date, the crucial question of how the three-dimensional organization of murein can be visualized remains unanswered. Since there is no methodology that allows investigation of the architecture of murein in intact cells, researchers have had to deduce the tertiary structure on the basis of indirect evidence, the unambiguous interpretation of which is often difficult.Currently, three models of the architecture of murein are discussed in the literature. (i) The predominant concept considers the peptidoglycan strands to run regularly and in parallel with the plasma membrane, furnishing a planar network (8,29). (ii) An analogous model assumes an irregular orientation of peptidoglycan strands in the planar network (33,34). (iii) The scaffold model proposes that peptidoglycan strands are oriented perpendicular to the plasma membrane (12, 13). The radial orientation of glycan strands within bacterial walls was hypothetically contemplated but rejected by Keleman and Rogers (32). It is important to note that the planar network models consider the thin gram-negative cell walls to consist of one major stress-bearing layer in combination with newly synthesized (innermost) and almost degraded (outermost) loosely...

The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I(50) values compared to those obtained previously against Plasmodium berghei- and E. coli-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I(50) values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.

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