We report the first cocrystal as an intermediate in a solidstate organic reaction wherein molecules of barbituric acid and vanillin assume a favorable orientation for the subsequent Knoevenagel condensation.The Knoevenagel condensation is an important carbon-carbon bond forming reaction. More than a hundred years after the original report by Knoevenagel, 1 Suzuki 2 and Kaupp 3 demonstrated an efficient and quantitative Knoevenagel condensation in the solid state achieved by milling. Other studies of solvent-free Knoevenagel condensation reactions soon followed. 4-10 The reaction of barbituric acid (barb) and vanillin (van) was even used as a model mechanochemical organic reaction for assessing energetics of milling, 11,12 to test twin-screw extrusion for solid-state organic synthesis, 13 and latest, to reveal a peculiar deviation of solid-state reaction kinetics from the one observed in solution, stemming from changes in the rheology of the milled sample. 14 However, studies of barb-van Knoevenagel condensation were thus far limited to ex situ reaction monitoring by, e.g., solution UV-Vis 11 or NMR spectroscopies. 14 In this work, we employ real-time in situ Raman spectroscopy monitoring 15,16 to reveal that the solid-state Knoevenagel condensation (Scheme 1) of barb and van proceeds through a cocrystal intermediate. In the cocrystal, packing of barb and van is such that molecules of barb are suitably positioned for the nucleophilic

Tetratopic porphyrin-based MOFs represent a particularly interesting subclass of zirconium MOFs due to the occurrence of several divergent topologies. The control over the target topology is a demanding task and reports often show products containing phase contamination. We demonstrate how mechanochemistry can be exploited for controlling the polymorphism in 12-coordinated porphyrinic zirconium MOFs, gaining pure hexagonal (shp) PCN-223 and cubic (ftw) MOF-525 phases in 20-60 minutes of milling. The reactions are mainly governed by the milling additives and the zirconium precursor. In situ monitoring by synchrotron powder X-ray diffraction (PXRD) revealed that specific reaction conditions resulted in the formation of MOF-525 as an intermediate, which rapidly converted to PCN-223 upon milling. Electron spin resonance (ESR) measurements revealed significant differences between the spectra of paramagnetic centers in two polymorphs, showing a potential of polymorphic Zr-MOFs as tunable supports in spintronics applications. Metal-organic frameworks (MOFs) received wide attention due to their potential for applications in gas storage 1-3 and separation, 4,5 catalysis, 6,7 drug delivery, 8 light-harvesting, 9,10 and destruction of harmful compounds such as chemical warfare agents. 11 Their superior performance stems from the existence of pores and channels enabling easy access of substrates to the active sites inside the MOF crystals. The use of MOFs as heterogeneous catalysts and catalysts supports is broadened after the introduction of Zr-MOFs based on zirconium [Zr6(OH)4O4] 12+ oxo-clusters and carboxylate linkers, 12 which provided a way to overcome challenges related to the robustness of MOFs under humid, acidic or basic media. 11,13 They also drew significant interest in an area of MOF-polymorphism. Zr-MOFs based on tetratopic tetrakis(4-carboxyphenyl) porphyrin (TCPP) linkers displayed unprecedented flexibility in topological ordering. They are known to exist in six different topologies, 14,15-22 12-connected cubic ftw (MOF-525) 21 and hexagonal shp (PCN-223), 16 8-connected sqc (PCN-225), 17 csq (PCN-222/MOF-545), 19,21 and scu (NU-902), 15 and 6-connected she (PCN-224). 20 Recent studies have been focused on establishing different reaction

Using tandem in situ monitoring and isotope-labeled solids, we reveal that mechanochemical ball-milling overcomes inherently slow solid-state diffusion through continuous comminution and growth of milled particles. This process occurs with or without a net chemical reaction and also occurs between solids and liquid additives which can be practically used for highly efficient deuterium labeling of solids. The presented findings reveal a fundamental aspect of milling reactions and also delineate a methodology that should be considered in the study of mechanochemical reaction mechanisms.

PurposeThe assessment of ovarian reserve by antral folicule count (AFC) following electrocoagulation versus suture after laparoscopic stripping of ovarian endometriomas. MethodsForty-five patients between 18 and 35 years, with unilateral endometriomas were randomly analyzed. Laparoscopic cystectomy was performed by the stripping method. Ovarian haemostasis was obtained either by suturing (group A, n = 23) or by bipolar electrocoagulation (group B, n = 22). AFC was performed by ultrasound on the third day of the three postoperative menstrual cycles. The sum of AFC was compared between sutured (A1) and electrocoagulated (B1) ovaries, as well as between intact ovaries of both groups (A0 -intact ovaries in sutured group; B0 -intact ovaries in electrocoagulated group). ResultsThe median of AFC was significantly lower in operated ovaries than in intact ovaries in both groups of patients, regardless of suturing (A1 median: 12 (range 9-19) versus A0 median: 21.0 (range 15-27), p<0.05) or electrocoagulation (B1:5.0 (2-10) vrs B0:18.5 (8-29) p<0.05). The median AFC was significantly higher in sutured ovaries than in electrocoagulated ovaries (A1:12 (9-19) vrs B1:5.0 (2-10), p<0.05). ConclusionOur preliminary data show that operation on ovarian endometriomas could reduce ovarian reserve. The AFC value suggests that the ovarian reserve was less reduced in sutured ovaries than in those electrocoagulated. Suturing as a method of haemostasis could be a better choice after stripping ovarian endometriomas.