Third molar development was assessed using a sample of 1,131 orthopantomograms from a Portuguese population. The methodology applied was the eight stages (A-H) method described by Demirjian et al. The final sample was made of 739 orthopantomograms, 387 (52.5%) of which belonging to females; age ranged between 6.1 and 22.5 years old (mean age = 14.49, S.D. = 4.37). For each developmental stage, mean age, standard deviation, and minimal and maximal age was assessed; evaluation of the rate formation of each tooth, according to sex, was calculated and data distribution expressed in percentiles for each stage; the probability of an individual being 16 was also evaluated. The relationship between tooth development and chronological age had a statistical significance for all teeth and both sexes (p < 0.0001). The data described may provide reference for forensic application and agree with the thesis that each population need specific data.

The study of structure-energetics relationships for active pharmaceutical ingredients has received considerable attention in recent years, due to its importance for the effective production and safe use of drugs. In this work the widely prescribed cholesterol-lowering drug simvastatin was investigated by combining experimental (combustion calorimetry and differential scanning calorimetry, DSC) and computational chemistry (quantum chemistry and molecular dynamics calculations) results. The studies addressed the crystalline form stable at ambient temperature (form I) and the liquid and gaseous phases. Heat capacity determinations by DSC showed no evidence of polymorphism between 293 K and the fusion temperature. It was also found that the most stable molecular conformation in the gas phase given by the quantum chemistry calculations (B3LYP-D3/cc-pVTZ) is analogous to that observed in the crystal phase. The molecular dynamics simulations correctly captured the main structural properties of the crystalline phase known from published single crystal X-ray diffraction results (unit cell dimensions and volume). They also suggested that, while preferential conformations are exhibited by the molecule in the solid at 298.15 K, these preferences are essentially blurred upon melting. Finally, the experiments and calculations led to enthalpies of formation of simvastatin at 298.15 K, in the crystalline (form I) ΔfH(m)(o) (cr I) = -1238.4 ± 5.6 kJ · mol(-1), liquid ΔfH(m)(o) (l) = -1226.4 ± 5.7 kJ · mol(-1), and gaseous ΔfH(m)(o) (g) = -1063.0 ± 7.1 kJ · mol(-1) states.

Simvastatin is one of the most widely used active pharmaceutical ingredients for the treatment of hyperlipidemias. Because the compound is employed as a solid in drug formulations, particular attention should be given to the characterization of different polymorphs, their stability domains, and the nature of the phase transitions that relate them. In this work, the phase transitions delimiting the stability domains of three previously reported simvastatin forms were investigated from structural, energetics, and dynamical points of view based on single crystal X-ray diffraction (SCXRD), hot stage microscopy (HSM), and differential scanning calorimetry (DSC) experiments (conventional scans and heat capacity measurements), complemented with molecular dynamics (MD) simulations. Previous assignments of the crystal forms were confirmed by SCXRD: forms I and II were found to be orthorhombic ( P222, Z'/ Z = 1/4) and form III was monoclinic ( P2, Z'/ Z = 2/4). The obtained results further indicated that (i) the transitions between different forms are observed at 235.9 ± 0.1 K (form III → form II) and at 275.2 ± 0.2 K (form II → form I) in DSC runs carried out at 10 K min and close to these values when other types of techniques are used (e.g., HSM). (ii) They are enantiotropic (i.e., there is a transition temperature relating the two phases before fusion at which the stability order is reversed), fast, reversible, with very little hysteresis between heating and cooling modes, and occur under single crystal to single crystal conditions. (iii) A nucleation and growth mechanism seems to be followed since HSM experiments on single crystals evidenced the propagation of an interface, accompanied by a change of birefringence and crystal contraction or expansion (more subtle in the case of form III → form II), when the phase transitions are triggered. (iv) Consistent with the reversible and small hysteresis nature of the phase transitions, the SCXRD results indicated that the molecular packing is very similar in all forms and the main structural differences are associated with conformational changes of the "ester tail". (v) The MD simulations further suggested that the tail is essentially "frozen" in two conformations below the III → II transition temperature, becomes progressively less hindered throughout the stability domain of form II, and acquires a large conformational freedom above the II → I transition. Finally, the fact that these transitions were found to be fast and reversible suggests that polymorphism is unlikely to be a problem for pharmaceutical formulations employing crystalline simvastatin because, if present, the III and II forms will readily convert to form I at ambient temperature.

Significant discrepancies in the literature data for the enthalpy of formation of gaseous anisole, ΔfHmo(PhOCH3, g), have fueled an ongoing controversy regarding the most reliable enthalpy of formation of the phenoxy radical and of the gas phase O-H bond dissociation enthalpy, DHo(PhO-H), in phenol. In the present work ΔfHmo(PhOCH3, g) was reassessed using a combination of calorimetric determinations and high-level (W2-F12) ab initio calculations. Static-bomb combustion calorimetry led to the standard molar enthalpy of formation of liquid anisole at 298.15 K, ΔfHmo(PhOCH3, l) = −(117.1 ± 1.4) kJ·mol(-1). The corresponding enthalpy of vaporization was obtained as, ΔvapHmo(PhOCH3) = 46.41 ± 0.26 kJ·mol(-1), by Calvet-drop microcalorimetry. These results give ΔfHmo(PhOCH3, g) = −(70.7 ± 1.4) kJ·mol(-1), in excellent agreement with ΔfHmo(PhOCH3, g) = −(70.8 ± 3.2) kJ·mol(-1), obtained from the W2-F12 calculations. The ΔfHmo(PhOCH3, g) here recommended leads to ΔfHmo(PhO•, g) = 55.5 ± 2.4 kJ·mol(-)1 and DH°(PhO-H) = 368.1 ± 2.6 kJ·mol(-1).

A procedure for the selective and reproducible preparation of the two known 4-hydroxybezaldehyde polymorphs was developed, based on the investigation of their relative stabilities by differential scanning calorimetry and solubility studies. From the obtained results, the stability domains of the two forms could be quantitatively represented in a Δ f G m °−T phase diagram. The system was found to be enantiotropic: form II is more stable than form I up to 277 ± 1 K; above this temperature, the stability order is reversed, and the fusion of form I subsequently occurs at 389.9 ± 0.2 K. Analysis of the crystal structures revealed that in both polymorphs the 4-hydroxybezaldehyde molecule exhibits the OH and C(O)H substituents in a Z conformation, which, according to B3LYP/6-31G(d,p) calculations, is more stable than the E conformation by only 0.4 kJ•mol −1 . The two forms are monoclinic, space group P2 1 /c, Z′/Z = 1/4, and have essentially identical densities at ambient temperature (1.358 g•cm −3 for form I; 1.357 g•cm −3 for form II), but differ in their packing. These differences are discussed, and the dissimilarities in the interactions sustaining the packing are highlighted using Hirshfeld surfaces. Finally, the relative stability and volumetric properties of both forms are analyzed by molecular dynamics simulations.