We demonstrate for the first time that 4H-1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4H-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors.

The reaction of [Mn(O2CMe)2] · 4H2O with pdH2 (1,3-propanediol) or mpdH2 (2-methyl-1,3-propanediol) in the presence of NaN3 in MeCN/py (py = pyridine) results in the formation of two new one-dimensional coordination polymers composed of a [MnIII 6MnII 11(μ4-O)8(μ3-N3)4]25+ octahedral unit. The peripheral ligation is completed by pd2- (or mpd2-), acetate, pyridine and μ-1,3-N3 - ligands. The latter bridges each Mn17 unit to its neighboring one, resulting in the formation of the two 1-D coordination polymers. Variable-temperature dc magnetic susceptibility studies indicate the existence of predominantly ferromagnetic interactions and a resulting giant ground state spin within the Mn17 units and intermolecular antiferromagnetic exchange interactions between the neighboring Mn17 units that result in diamagnetic ground spin states for both polymeric compounds.

The crystal structure of the title compound, C9H 12O4S, was determined in order to investigate the effect of the eclipsed O atoms on the bond length of the vicinal quaternary C atoms. The two quaternary C atoms of the noradamantane skeleton and the two O atoms to which they are connected all located essentially in the same plane (maximum deviation = 0.01 Å), resulting in an eclipsed conformation of the C - O bonds. The C - C bond of the quaternary C atoms is 1.581 (3) Å, considerably longer than the other C - C bonds of the molecule due to the stretch of the cage structure.

The title compound, C18H24I2, has an adamantanoid structure with tetra-hedral cages having four C atoms lying on the same plane [(I-)C-C-C-C(-I) torsion angle = 0°]. The plane is extended by the two I atoms, each having a deviation of 1.0 (6) Å [C-C-C-I torsion angle = 178.9 (4)°]. The central C-C bond connecting the two quaternary carbons seems enlarged [1.593 (9) Å] in comparison to the corresponding bond in [2]diadamantane [1.554 (3) Å]. This is attributed to the presence of the electronegative I atoms, which affect inductively the C atoms of the four-C-atom plane, making the central C-C bond weaker.

Stille coupling of 3,5-bis(5-bromothien-2-yl)-4H-1,2,6-thiadiazin-4-one (10) with 2-(tri-n-butylstannyl)thiazole and Pd(Ph 3 P) 2 Cl 2 in PhMe, at ca. 110 ◦ C, for 2 h, gave 3,5-bis[5-(thiazol-2-yl)thien-2-yl]-4H-1,2,6-thiadiazin-4-one (9) in 81% yield. The latter is evaluated for its electronic properties.

Stille coupling of 5-chloro-4-oxo-4H-1,2,6-thiadiazin-3-yl trifluoromethanesulfonate (7) with tributyl(3-n-hexylthien-2-yl)stannane and Pd(Ph 3 P) 2 Cl 2 in PhMe at ca. 20 ◦ C, for 24 h gave 3-chloro-5-(3-n-hexylthien-2-yl)-4H-1,2,6-thiadiazin-4-one (9) with a 60% yield. The latter is a potentially useful building block for the synthesis of oligomeric and polymeric donors for organic photovoltaics.

Cancer is one of the leading fatal diseases in the western world and many approaches have been proposed for both its treatment and prevention. Several of these approaches are dealing with the use of chemicals or with the use of signaling molecules that interfere with critical pathways in cancer progression. Yet, there is still a lot to be learned for the biology and mechanisms of oncogenesis, tumor progression, and tumor biology in general. What that has been neglected throughout the years is the understanding of biological systems from the physical perspective and the understanding of their mechanisms from the physical point of view. Since living systems could be considered as physical systems, there exists the possibility of examining biological phenomena under this perspective. In the present work we use computational and physical approaches to study and model the tolerance limits and mechanics of cell membranes. Our scope is to gain a better understanding of these phenomena and potentially use them for therapeutic purposes, since we are referring to tumor cells.

This study investigated whether switching from a diet rich in saturated fatty acids (SAFAs) to a diet rich in monounsaturated fatty acids (MUFAs) or to one with equal amounts of MUFAs-SAFAs favorably affects the lipid profile of hypercholesterolemic mice. C57BL/6 mice (n = 82) were allocated into 4 groups. The first group (control, n = 10) was fed standard chow. The 3 remaining groups (n = 24 mice/group) were fed a SAFA-rich diet for 8 weeks and were then allocated for 16 weeks to either a MUFA-rich diet, an equal in MUFAs-SAFAs-rich diet, or continued the previous SAFA-rich diet. After 8 weeks, mice consuming SAFA-rich diet had increased weight, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) levels (P <.05 vs baseline). At week 24, MUFA-rich and MUFA-SAFA rich diets decreased TC and low-density lipoprotein cholesterol (LDL-C) levels (P <.05) compared with week 8. In conclusion, switching to MUFA-rich diets or substituting half of the SAFAs with MUFAs can reverse diet-induced-hypercholesterolemia.

(Figure Presented) Singles networks: The use of 1,3-propanediol and of 2-methyl-1,3-propanediol in manganese carboxylate chemistry leads to two new 3D coordination polymers with an unprecedented Mn19 repeating unit. The polymers have open framework structures with nanometer-sized cavities (see picture; Na not visible, Mn blue, O red, C gray). The Mn19 units have a ground spin state of S = 23/2 and behave as single-molecule magnets.

A large [Mn10Na]4 loop-of-loops aggregate was prepared from the use of 1,3-propanediol (pdH2) in manganese carboxylate chemistry. It is constructed from four [Mn10(μ 3-O)2(O2CMe)13(pd) 6(py)2]- loops linked through Na+ ions and exhibits a saddlelike topology. Magnetic characterization showed that the Mn10 loop has an S ∼ 4 ground-state spin and displays frequency-dependent in-phase and out-of-phase alternating current signals and also hysteresis loops that, however, are not typical of single-molecule magnets because of the existence of intermolecular interactions between the Mn 10 units.

Invited for the cover of this issue is Anastasios Tasiopoulos from the University of Cyprus. The cover image shows photos from the southwestern Cyclades island group of the Aegean Sea, which contain a wealth of minerals and rocks. Some of these exhibit porous structures and interesting magnetic properties.

The synthesis and characterization of {[Co9(INA)18(H2O)6]·11DMF·15H2O}∞ (Co9-INA·11DMF·15H2O) (INA- = the anion of isonicotinic acid) is reported. It exhibits a rigid 3D-porous structure with a Co9 repeating unit consisting of four [CoII2(μ-O2CR)2(μ-H2O)] subunits (two unique) linked through bridging INA- ligands to an isolated CoII ion (half unique). The [CoII2] dimers and the isolated CoII ion have assembled to create a trinodal (6,7,8)-coordinated network with point symbol (32.411.56.62)2(32.418.54.64)2(34.44.54.63). Gas sorption studies revealed that Co9-INA exhibits 910 m2 g-1 BET area, 4.2 mmol g-1 CO2 uptake at 273 K/1 bar, and 6.7 CO2/CH4 selectivity at zero coverage. Furthermore, Co9-INA displays capability for exchange of the guest solvent molecules by various organic molecules in a single-crystal to single-crystal fashion. Direct and alternating current magnetic susceptibility studies revealed the existence of dominant antiferromagnetic interactions between the Co2+ ions that result in a paramagnetic ST = 3/2 spin ground state value. Overall, this work emphasizes the potential of relatively simple and inexpensive polytopic ligands, such as isonicotic acid, to stabilize microporous MOFs with significant CO2 sorption capacity.

A new Cu2+ complex that was isolated from the initial use of 5-((pyridin-4-ylmethylene)amino)isophthalic acid (PEIPH2) in 3d metal-organic framework (MOF) chemistry is reported. Complex {[Cu3(PEIP)2(5-NH2-mBDC)(DMF)]·7DMF}∞ denoted as Cu-PEIP·7DMF was isolated from the reaction of Cu(NO3)2·2.5H2O with PEIPH2 in N,N-dimethylformamide (DMF) at 100 °C and contains both the PEIP2- ligand and its 5-NH2-mBDC2- fragment. After the structure and properties of Cu-PEIP were known an analogous complex was prepared by a rational synthetic method that involved the reaction of Cu(NO3)2·2.5H2O, 5-((pyridin-4-ylmethyl)amino)isophthalic acid (PIPH2-the reduced analogue of PEIPH2) and 5-NH2-mBDCH2 in DMF at 100 °C. Cu-PEIP comprises two paddle-wheel [Cu2(COO)4] units and exhibits a 3D-framework with a unique trinodal underlying network and point symbol (4.52)4(42·54·64·83·92)2(52·84). This network consists of pillared kgm-a layers containing a hexagonal shaped cavity with a relatively large diameter of ∼8-9 Å surrounded by six trigonal shaped ones with a smaller diameter of ∼4-5 Å and thus resembles the structure of HKUST-1. Gas sorption studies revealed that Cu-PEIP exhibits a 1785 m2 g-1 BET area as well as high CO2 sorption capacity (4.75 mmol g-1 at 273 K) and CO2/CH4 selectivity (8.5 at zero coverage and 273 K).

The missing VIV11VV7 oxidation-state member of the polyoxooctadecavanadate(IV/V) - azide family of inorganic host-guest systems has been incorporated in a NaI-containing 3D architecture; the complex shows remarkable inhibition properties on human platelet aggregation and antitumoural activity against cancer cell lines

The initial use of 1,3-propanediol in mixed Mn/3d cluster chemistry has led to a Mn III 28Mn II 8Ni II 4 molecular aggregate which consists of two Mn III 8Ni 2 loops and two Mn III 6Mn II 4 supertetrahedral units and displays a high ground spin state value S T = 26 ± 1.

Two new Mn15 clusters consisting of a supertetrahedron which is incorporated in a loop are reported. The reactions of [Mn(O2CEt) 2]·2H2O with the diols 1,3-propanediol (H 2pd) or 2-methyl-1,3-propanediol (H2mpd) in the presence of KX (X = CN-, Cl-, Br-, NO3 -, ClO4 -, OCN-, SCN-) afforded compounds [Mn15K(μ4-O)4(O 2CEt)11(pd)12(py)2] (1) and [Mn 15K(μ4-O)4(O2CEt) 11(mpd)12(py)2] (2). The structural core of 1 and 2 consists of a Mn11 loop and a Mn9K supertetrahedron sharing a Mn5 triangle. To the best of our knowledge, the structural motif of a supertetrahedron incorporated in a loop appears for the first time in metal cluster chemistry. Variable-temperature, solid-state direct current (dc) magnetic susceptibility studies in the 300-5 K range showed that the χMT value increases with decreasing T suggesting the existence of predominant ferromagnetic exchange interactions and a relatively large ground state spin. This was confirmed by field-variable temperature magnetization measurements which were fitted using a matrix diagonalization method to give S∼ 23/2, g = 1.92(1) and D = -0.071(2) cm-1. In addition, compound 1 displays frequency-dependent alternating current (ac) signals suggesting single-molecule magnetism (SMM) behaviour. This was proven by magnetization vs. dc field sweeps on single-crystals of 1·0.7py·1. 3MeCN, which displayed sweep rate- and temperature-dependent hysteresis loops

A [Mn lll 11Mn ll 6(μ 4-O) 8(μ 3-L) 4] 25+ (L = N 3 - or OCN -) octahedral unit is reported, occurring within 1D (1)∞ and 2D (2)∞ coordination polymers, as well as the corresponding 0D discrete cluster 3. It possesses a giant ground-state spin value, determined in the case of 3 to be S= 37, the second largest to be reported to date. In addition, compound 3 displays single-molecule magnet (SMM) behavior, and is thus the largest-spin SMM.

Despite the progress in the area of food safety, foodborne diseases still represent a massive challenge to the public health systems worldwide, mainly due to the substantial inefficiencies across the farm-to-fork continuum. Here, we report the development of a nano-carrier platform, for the targeted and precise delivery of antimicrobials for the inactivation of microorganisms on surfaces using Engineered Water Nanostructures (EWNS). An aqueous suspension of an active ingredient (AI) was used to synthesize iEWNS, with the ‘i’ denoting the AI used in their synthesis, using a combined electrospray and ionization process. The iEWNS possess unique, active-ingredient-dependent physicochemical properties: i) they are engineered to have a tunable size in the nanoscale; ii) they have excessive electric surface charge, and iii) they contain both the reactive oxygen species (ROS) formed due to the ionization of deionized (DI) water, and the AI used in their synthesis. Their charge can be used in combination with an electric field to target them onto a surface of interest. In this approach, a number of nature-inspired antimicrobials, such as H2O2, lysozyme, citric acid, and their combination, were used to synthesize a variety of iEWNS-based nano-sanitizers. It was demonstrated through foodborne-pathogen-inactivation experiments that due to the targeted and precise delivery, and synergistic effects of AI and ROS incorporated in the iEWNS structure, a pico-to nanogram-level dose of the AI delivered to the surface using this nano-carrier platform is capable of achieving 5-log reductions in minutes of exposure time. This aerosol-based, yet ‘dry’ intervention approach using iEWNS nano-carrier platform offers advantages over current ‘wet’ techniques that are prevalent commercially, which require grams of the AI to achieve similar inactivation, leading to increased chemical risks and chemical waste byproducts. Such a targeted nano-carrier approach has the potential to revolutionize the delivery of antimicrobials for sterilization in the food industry.

Quantitative NMR spectroscopy is always an attractive goal as the identity and quantity could be simultaneously determined. Although significant advancements have been achieved in this field it is common that all reported quantitative NMR methods perform the analysis by utilizing the average integral intensities of selected signals. During the calculation of the area under NMR peaks several response problems can occur which should always be treated carefully to overcome inaccuracies. In the method proposed in this work the quantitative information is obtained utilizing the measurement of selected protons chemical shift displacements which is a quite straightforward and highly reproducible process. The 1H NMR spectra of multiple fluoroquinolone (FQ) solutions revealed that the chemical shifts of protons, especially the aromatic ones, were concentration dependent for all tested compounds, as a result of extensive self-association phenomena. In the present work a novel methodology is described for the quantitation of several FQs based on this dependence. The proposed method was applied to Ciprofloxacin solutions over a wide range of concentrations. Evaluation of the obtained data presented acceptable characteristics regarding accuracy, precision, and robustness. The applicability limitations of this method were found to be posed by current instrumentation, mainly by the magnetic field frequency e.g. the slope of the response function achieved with a 400 MHz instrument was twice the one achieved at 200 MHz. The pH effect was negligible from pD 2.5 to 5.5. The phenomenon appeared in a pattern that can be applied for a plethora of drug categories revealing self-association phenomena in a range of concentration determined by the magnet strength of the instrument.

Three new octanuclear compounds were prepared from reactions of [Mn(O2CR)2]·2H2O (R = Et or Ph) with the diols 1,3-propanediol (pdH2) or 2-methyl-1,3-propanediol (mpdH2) in the presence of NaN3. All three compounds [Mn8(N3)4(O2CR)6(L)4(py)6] (L = pd2-, R = Et 1; L = mpd2-, R = Et 2; L = pd2-, R = Ph 3) (py = pyridine) possess a novel near-planar, rod-like topology. Dc and ac magnetic susceptibility studies in the 2-300 K range for complexes 1 and 2 revealed the presence of dominant antiferromagnetic exchange interactions, leading to diamagnetic ground spin states.