Charge-Density Distribution and Electrostatic Flexibility of ZIF‑8 Based on High-Resolution X‑ray Diffraction Data and Periodic Calculations

The electron-density distribution in a prototypical porous coordination polymer ZIF-8 has been obtained in an approach combining high-resolution X-ray diffraction data and Invariom refinement. In addition, the periodic quantum-chemical calculation has been used to describe the theoretical density features of ZIF-8 in the same geometry (<b>m1</b>) and also in a “high-pressure” form of ZIF-8 (<b>m2</b>) characterized by conformational change with respect to the methylimidazolate linker. A thorough comparison of the electronic and electrostatic properties in two limiting structural forms of ZIF-8 proposes additional aspects on diffusion and adsorption processes occurring within the framework. The dimensions of the four-membered (FM) and six-membered (SM) apertures of the β cage are reliably determined from the total electron-density distribution. The analysis shows that FM in <b>m2</b> becomes competitive in size to the SM aperture and should be considered for the diffusion of small molecules and cations. Bader’s topological analysis (quantum theory of atoms in molecules) shows similar properties of both ZIF-8 forms. On the other hand, analysis of their electrostatic properties reveals tremendous differences. The study suggests exceptional electrostatic flexibility of the ZIF-8 framework, where small conformational changes lead to a significantly different electrostatic potential (EP) distribution, a feature that could be important for the function and dynamics of the ZIF-8 framework. The cavity surface in <b>m1</b> contains 38 distinct regions with moderately positive, negative, or neutral EP and weakly positive EP in the cavity volume. In contrast to <b>m1</b>, the <b>m2</b> form displays only two regions of different EP, with the positive one taking the whole cavity surface and the strong negative one localized entirely in the FM apertures. The EP in the cavity volume is also more positive than that in <b>m1</b>. A pronounced influence of the linker reorientation on the EP of the ZIF-8 forms is related to the high symmetry of the system and to an amplification of the electrostatic properties by cooperative effects of the proximally arranged structural fragments

Cytotoxic 14-Membered Macrolides from a Mangrove-Derived Endophytic Fungus, <i>Pestalotiopsis microspora</i>

Seven new 14-membered macrolides, pestalotioprolides C (<b>2</b>), D–H (<b>4</b>–<b>8</b>), and 7-<i>O</i>-methylnigrosporolide (<b>3</b>), together with four known analogues, pestalotioprolide B (<b>1</b>), seiricuprolide (<b>9</b>), nigrosporolide (<b>10</b>), and 4,7-dihydroxy-13-tetradeca-2,5,8-trienolide (<b>11</b>), were isolated from the mangrove-derived endophytic fungus <i>Pestalotiopsis microspora</i>. Their structures were elucidated by analysis of NMR and MS data and by comparison with literature data. Single-crystal X-ray diffraction analysis was used to confirm the absolute configurations of <b>1</b>, <b>2</b>, and <b>10</b>, while Mosher’s method and the TDDFT-ECD approach were applied to determine the absolute configurations of <b>5</b> and <b>6</b>. Compounds <b>3</b>–<b>6</b> showed significant cytotoxicity against the murine lymphoma cell line L5178Y with IC₅₀ values of 0.7, 5.6, 3.4, and 3.9 μM, respectively, while compound <b>5</b> showed potent activity against the human ovarian cancer cell line A2780 with an IC₅₀ value of 1.2 μM. Structure–activity relationships are discussed. Coculture of <i>P. microspora</i> with <i>Streptomyces lividans</i> caused a roughly 10-fold enhanced accumulation of compounds <b>5</b> and <b>6</b> compared to axenic fungal control