THE EFFECT OF THE PROTONATION STATE OF THE HYDROXYL-ETHYLTHIAMIN DIPHOSPHATE INTERMEDIATE, HETHDP, ON THE ENZYME-SUBSTRATE INTERACTIONS AND THEIR CONSEQUENCES ON THE BIOSYNTHESIS OF R-PHENYLACETYLCARBINOL, R-PAC, BY THE ACETOHYDROXY ACID SYNTHASE, AHAS, IS ADDRESSED BY MOLECULAR DYNAMICS SIMULATIONS. IT IS FOUND THAT THE FORM OF HETHDP, WHICH FAVORS THE FORMATION OF R-PAC, IS THAT HAVING THE 4-AMINOPYRIMIDINE RING WITH THE N1 ATOM PROTONATED AND THE N4 ATOM AS AMINOPYRIMIDINIUM ION. UNDER THIS FORM BOTH ACTIVE SITES OF AHAS HAVE THE ABILITY TO PERFORM THE CATALYSIS, UNLIKE THAT OBSERVED FOR THE OTHER POSSIBLE PROTONATION STATES OF N1? AND N4? ATOMS.

THE MOLECULAR STRUCTURE OF THE LIQUID?VAPOR INTERFACES OF AQUEOUS SOLUTIONS OF ALKALI METAL HALIDES AND METHYL ISOBUTYL CARBINOL (MIBC, (CH3)2CHCH2COCH3) IS DETERMINED BY USING MOLECULAR DYNAMICS SIMULATIONS WITH POLARIZABLE FORCE FIELDS FOR THE FIRST TIME. THE SALTS ARE CHLORIDES, AND IODIDES, SOME OF WHICH ARE FOUND IN RAW AND PARTIALLY DESALINATED SEAWATER INCREASINGLY USED IN FLOTATION OPERATIONS IN REGIONS AFFECTED BY SEVERE AND PROLONGED DROUGHT. THE DENSITY PROFILES AT THE INTERFACES SHOW THAT ALL IONS PREFER THE INTERFACE; HOWEVER, WITH MIBC, NON-POLARIZABLE IONS, GENERALLY SMALL ONES, ARE INCREASINGLY PUSHED INTO THE LIQUID BULK. A FEW IONS OF COMPARATIVELY LESS IONIC NACL THAN KCL AND CSCL, PERSIST AT THE INTERFACE, CONSISTENT WITH SPECTROSCOPY OBSERVATIONS. ON THE OTHER HAND, STRONGLY POLARIZABLE IONS SUCH AS I? ALWAYS SHARE THE INTERFACE WITH MIBC. IN THE PRESENCE OF CHLORIDES, THE FROTHER CHAINS AT THE INTERFACE STRETCH SLIGHTLY MORE TOWARD VAPOR THAN IN FRESHWATER; HOWEVER, IN THE PRESENCE OF IODIDES, THE CHAINS STRETCH SO MUCH THAT THEY BECOME ORTHOGONAL TO THE INTERFACE, GIVING RISE TO A WELL-PACKED MONOLAYER, WHICH IS THE MOST EFFECTIVE CONFIGURATION. THE DOMINANT WATER CONFIGURATIONS AT THE INTERFACE ARE DOUBLE DONOR AND SINGLE DONOR, WITH HYDROGEN ATOMS POINTING TOWARD THE LIQUID, CONSISTENT WITH STUDIES WITH SUM-FREQUENCY GENERATION EXPERIMENTS AND EXTENSIVE AB INITIO SIMULATIONS. THIS PICTURE CHANGES RADICALLY IN THE PRESENCE OF MIBC AND SALTS. DEPENDING ON THE HALIDE AND MIBC CONCENTRATION, THE DIFFERENT MOLECULAR CONFIGURATIONS AT THE INTERFACE LEAD TO VERY DIFFERENT SURFACE TENSIONS. THE STRUCTURE AND PROPERTIES OF THESE NEW SALT-RICH INTERFACES AND THEIR IMPACT ON THE LOCATION AND ARRANGEMENT OF FROTHER MOLECULES SHOULD SERVE THE FLOTATION PRACTITIONER, ESPECIALLY IN THE SEARCH FOR THE BEST FROTHER AND DOSING IN POOR-QUALITY WATER

THE STAUDINGER KETENE-IMINE [2?+?2] CYCLOADDITION PROVIDES AN EFFICIENT STRATEGY TO PRODUCE POLYSUBSTITUTED ?-LACTAM RINGS, RESULTING IN TWO PAIRS OF ENANTIOMERS WITH CIS/TRANS CONFIGURATIONS. THIS REACTION IS ALSO BIOMEDICALLY RELEVANT AS IT PROVIDES ACCESS TO CARBAPENEM ANTIBIOTICS. GIVEN THE IMPORTANCE OF CONTROLLING THE DIASTEREOSELECTIVITY AND ENANTIOSELECTIVITY OF THIS TRANSFORMATION, OUR COMPUTATIONAL EFFORTS FOCUSED ON INVESTIGATING THE EFFECT OF ORIENTED EXTERNAL ELECTRIC FIELDS (OEEFS) ON THE STAUDINGER REACTION BETWEEN TERT-BUTYLCYANOKETENE AND BENZYLIDENEANILINE. WE INITIALLY STUDIED THE THEORETICAL MECHANISM FOR THIS REACTION IN THE ABSENCE OF ELECTRIC FIELDS IN GAS-PHASE CONDITION. THEN, WE PERFORMED IN-SILICO STUDIES TO EVALUATE THE EFFECT OF ELECTRIC FIELDS ON THE OUTCOME OF THE STAUDINGER REACTION. OUR RESULTS INDICATED THAT APPLYING AN ELECTRIC FIELD ALONG ANY OF THE THREE CARTESIAN AXES LEADS TO A KINETIC AND THERMODYNAMIC EFFECT FAVORING THE CIS ?-LACTAM PRODUCTS OVER THE TRANS, MIRRORING THE REACTION WITHOUT AN EXTERNAL ELECTRIC FIELD. REMARKABLY, OUR RESULTS ALSO SHOWED THAT THE EFFECTS OF OEEFS ALONG THE Y-AXIS IS THE SOLE CONTRIBUTOR TO ENANTIOSELECTIVITY CONTROL. THUS, WE OBSERVED THAT IN THE STAUDINGER REACTION BETWEEN TERT-BUTYLCYANOKETENE AND BENZYLIDENEANILINE, THE OEEF INFLUENCES THE KINETICS, THERMODYNAMICS AND ENANTIOSELECTIVITY, WHILE THE DIASTEREOSELECTIVITY REMAINS UNAFFECTED.

THE RESISTANCE OF KAOLIN AGGREGATES TO SHEARING IN WATER CLARIFICATION AND RECOVERY OPERATIONS IS A CRITICAL INPUT IN DESIGNING THICKENER FEED WELLS. A RECENTLY FORMULATED BUT ALREADY AVAILABLE CRITERION IS USED TO DETERMINE THE SHEAR STRENGTH OF FLOCCULATED KAOLIN AGGREGATES. THE FLOCCULANT IS A HIGH MOLECULAR WEIGHT ANIONIC POLYELECTROLYTE. THE RESISTANCE OF THE AGGREGATES IS EVALUATED AS A FUNCTION OF FLOCCULATION TIME, FLOCCULANT DOSAGE, AND WATER QUALITY. THE DETERMINATION IS BASED ON A STANDARDIZED EXPERIMENTAL METHOD. FIRST, THE TIME EVOLUTION OF THE AVERAGE SIZE OF KAOLIN FLOCS IS MEASURED WHEN AGGREGATES ARE EXPOSED TO INCREMENTAL SHEAR RATES FROM A PREDETERMINED BASE VALUE. THEN, THE RESULTS ARE FITTED TO A PSEUDO-FIRST-ORDER MODEL THAT ALLOWS DERIVING A CHARACTERISTIC VALUE OF THE SHEAR RATE OF RUPTURE ASSOCIATED WITH THE UPPER LIMIT OF THE STRENGTH OF THE AGGREGATES. IN SEAWATER, AT A GIVEN DOSE OF FLOCCULANT, THE STRENGTH OF THE AGGREGATES INCREASES WITH TIME UP TO A MAXIMUM; HOWEVER, AT LONGER TIMES, THE RESISTANCE DECREASES UNTIL IT SETTLES AT A STABLE VALUE CORRESPONDING TO STABLE AGGREGATES IN SIZE AND STRUCTURE. A HIGHER FLOCCULANT DOSAGE LEADS TO STRONGER AGGREGATES DUE TO MORE BRIDGES BETWEEN PARTICLES AND POLYMERS, LEADING TO A MORE INTRICATE AND RESISTANT PARTICLE NETWORK. IN INDUSTRIAL WATER WITH VERY LOW SALT CONTENT, THE RESISTANCE OF THE KAOLIN AGGREGATES IS HIGHER THAN IN SEAWATER FOR THE SAME DOSE OF FLOCCULANT. THE SALT WEAKENS THE RESISTANCE OF THE AGGREGATES AND WORKS AGAINST THE EFFICIENCY OF THE FLOCCULANT. THE STUDY SHOULD BE OF PRACTICAL INTEREST TO CONCENTRATION PLANTS THAT USE SEAWATER IN THEIR OPERATIONS.

THE BIOSYNTHESIS OF R-PHENYLACETYLCARBINOL (R-PAC) BY THE ACETOHYDROXY ACID SYNTHASE, (AHAS) IS ADDRESSED BY MOLECULAR DYNAMICS SIMULATIONS (MD), HYBRID QUANTUM MECHANICS/MOLECULAR MECHANICS (QM/MM), AND QM/MM FREE ENERGY CALCULATIONS. THE RESULTS SHOW THE REACTION STARTS WITH THE NUCLEOPHILIC ATTACK OF THE C2? ATOM OF THE HETHDP INTERMEDIATE ON THE C? ATOM OF THE CARBONYL GROUP OF BENZALDEHYDE SUBSTRATE VIA THE FORMATION OF A TRANSITION STATE (TS1) WITH THE HETHDP INTERMEDIATE UNDER 4-AMINOPYRIMIDIUM (APH+) FORM. THE CALCULATED ACTIVATION FREE ENERGY FOR THIS STEP IS 17.4 KCAL MOL-1 AT 27 °C. FROM THIS POINT, THE REACTION CONTINUES WITH THE ABSTRACTION OF H? ATOM OF THE HETHDP INTERMEDIATE BY THE O? ATOM OF BENZALDEHYDE TO FORM THE INTERMEDIATE I. THE REACTION IS COMPLETED WITH THE CLEAVAGE OF THE BOND C2?-C2 TO FORM THE PRODUCT R-PAC AND TO REGENERATE THE YLIDE INTERMEDIATE UNDER THE APH+ FORM, ALLOWING IN THIS WAY TO REINITIATE TO THE CATALYTIC CYCLE ONCE MORE. THE CALCULATED ACTIVATION BARRIER FOR THIS LAST STEP IS 15.9 KCAL MOL-1 AT 27 °C.

METHYL ISOBUTYL CARBINOL (MIBC) IS A HIGH-PERFORMANCE SURFACTANT WITH UNUSUAL INTERFACIAL PROPERTIES MUCH APPRECIATED IN INDUSTRIAL APPLICATIONS, PARTICULARLY IN MINERAL FLOTATION. IN THIS STUDY, THE STRUCTURE OF AIR?LIQUID INTERFACES OF AQUEOUS SOLUTIONS OF MIBC-NACL IS DETERMINED BY USING MOLECULAR DYNAMICS SIMULATIONS EMPLOYING POLARIZABLE AND NONPOLARIZABLE FORCE FIELDS. DENSITY PROFILES AT THE INTERFACES AND SURFACE TENSION FOR A WIDE RANGE OF MIBC CONCENTRATIONS REVEAL THE KEY ROLE OF POLARIZABILITY IN DETERMINING THE SURFACE SOLVATION OF CL? IONS AND THE EXPULSION OF NON-POLARIZABLE NA+ IONS FROM THE INTERFACE TO THE LIQUID BULK, IN AGREEMENT WITH SPECTROSCOPIC EXPERIMENTS. THE ORIENTATION OF MIBC MOLECULES AT THE WATER LIQUID?VAPOR INTERFACE CHANGES AS THE CONCENTRATION OF MIBC INCREASES, FROM PARALLEL TO THE INTERFACE TO PERPENDICULAR, LEADING TO A WELL-PACKED MONOLAYER. SURFACE TENSION CURVES OF FRESH WATER AND AQUEOUS NACL SOLUTIONS IN THE PRESENCE OF MIBC INTERSECT AT A REPRODUCIBLE SURFACTANT CONCENTRATION FOR A WIDE RANGE OF SALT CONCENTRATIONS. THE SIMULATION RESULTS FOR A 1 M NACL AQUEOUS SOLUTION WITH POLARIZABLE WATER AND IONS CLOSELY CAPTURE THE MIBC CONCENTRATION AT THE INTERCEPT. THE INCREASE IN SURFACE TENSION OF THE AQUEOUS MIBC/NACL MIXTURE BELOW THE CONCENTRATION OF MIBC AT THE INTERSECTION SEEMS TO ORIGINATE IN A DISTURBANCE OF THE INTERFACIAL HYDROGEN BONDING STRUCTURE OF THE SURFACE LIQUID WATER CAUSED BY NA+ IONS ACTING AT A DISTANCE AND NOT BY ITS PRESENCE ON THE INTERFACE.