An investigation into some mechanistic aspects of estrogen biosynthesis

The mechanistic aspects of the 19-hydroxy1ation and aromatization of androgens were investigated. Fungal, bacterial and mammalian enzymatic activities were studied in this regard . The fungus Pell i cular~ fi1amentosa metabolized androst-4-ene-3 , 17-dione to the corresponding 110<' , 11 f and 14 0( hydroxylated derivatives. No ~19- hydroxylated products were isolated, although this transformation was previously observed for the C21-steroids . The intestinal bacterium Clostridi um paraputrific~ had been reported to aromatize androsten-4-ene-3,17-dione. In the present study, however, only the ring A reduced products , 17(3 - hydroxy-5f -andro8tane- 3-one and 5f-androstane-3,17-dione , were recovered . Human placental microsomes contain substantial aromatase activity and were employed in an effort to elucidate some of the mechanistic details of aromatization. Selectively deuterated steroidal substrates were employed as a probe in order to distinguish b'!tween certain of the mechanisms proposed for aromatization . Retention of deuterium at C4 and C6 was observed. It was concluded that no free intermediates allowing for loss of hydrogen from either of these two positions are implicated in this process . The involvement of a Schiff base enzyme-sup strate complex in aromatization was examined using the substrate 17f - hydroxyandrost-4-ene-3-one- 3_ 1BO. Since no loss of label was ob~erved, the implication of a Schiff base was discounted . Mixed label1ir~ studies were performed in order to determine if hydroxylation at C19 is a rate-determining process in aromatization . Isotope effects of 2 .1 and 1.7 were determined for the conversion of 17f - hydroxyandrost-4-ene-J-one-19,19,19-dJ and -19-dl respectively to estrogens. It was concluded from this that 19-hydroxylation is at l east a partially rate-determinjng process in aromatization. A homoenb~ation mechanism for 19-hydroxylation was not supported by the data obtained in this s tudy. In vitro 1JC NMR monitoring using l7f-hydroxyandrost-4-ene-Jone- 19-l3C was found not to be a successful approach in the study of steroid transformations, owing in part t o their low solubility in the incubation medium.

Phospha-adamantanes as ligands for palladium-catalyzed cross-coupling reactions

New and robust methodologies have been designed for palladium-catalyzed crosscoupling reactions involving·a novel·class oftertiary phosphine ligand incorporating a phospha-adamantane framework. It has been realized that bulky, electron-rich phosphines, when used as ligands for palladium, allow for cross-coupling reactions involving even the less reactive aryl halide substrates with a variety of coupling partners. In an effort to design new ligands suitable for carrying out cross-coupling transformations, the secondary phosphine, 1,3,5,7-tetramethyl-2,4,8-trioxa-6phosphaadamantane was converted into a number of tertiary phosphine derivatives. The ability of these tertiary phosphaadamantanes to act as effective ligands in the palladiumcatalyzed Suzuki cross-coupling was examined. 1,3,5,7-Tetramethyl-6-phenyl-2,4,8trioxa- 6-phosphaadamantane (PA-Ph) used in combination with Pdz(dba)3permitted the reaction of an array of aryl iodides, bromides and chlorides with a variety arylboronic acids to give biaryls in good to excellent yields. Subsequently, palladium complexes of PA-Ph were prepared and isolated in high yields as air stable palladium bisphosphine complexes. Two different kinds of crystals were isolated and upon characterization revealed two complexes, Pd(PA-Ph)z.dba and Pd(PA-Ph)zOz. Preliminary screening for their catalytic activity indicated that the former is more reactive than the latter. Pd(PAPh) z.dba was applied as the catalyst for Sonogashira cross-coupling reactions of aryl iodides and bromides and in the reactions of aryl bromides and chlorides with ketones to give a-arylated ketones at mild temperatures in high yields.

Synthetic studies on prostaglandins: "synthesis of a new thia-PGEI analog"

A PGE1 analog, namely (±)-trans-2-(6'-carbomethoxyhexyl)-3- (E-3"-thia-1 "-octene)-4-hydroxycyclopentanone 71, has been prepared for the first time. Towards the synthesis of this compound, several synthetic approaches aimed at the preparation of the required acetylenic and E-halovinylic sulfides as building blocks were investigated. Among all the methods examined, it appeared evident that the best route to ethynyl n.pentyl sulfide 81 is via a double dehydrohalogenation of the corresponding 1,2-dibromoethyl sulfide with sodium amide in liquid ammonia. In addition, the isomerically pure E-2-iodoethenyl n.pentyl sulfide 85 is conveniently prepared in high yield and stereoselectivity by hydrozirconation-iodination of the terminal ethynyl sulfide 81. The classical hydroalumination and hydroboration reactions for the preparation of vinyl halides from alkynes gave only small yields when applied as methods towards the synthesis of 85 . The building block 2-(6'-carbomethoxyhexyl)-4-hydroxy-2- cyclopentenone (±)-1 carrying the upper side-chain of prostaglandin E 1 was prepared by a step-wise synthesis involving transformations of compounds possessing the required carbocyclic framework (see scheme 27). The synthesis proved to be convenient and gave a good overall yield of (±)-1 which was protected as the TH P-derivative 37 or the siloxy derivative 38. With the required building blocks 81 and 37 in hand, the target 1S-thia-PGE1 analog (±)-71 was prepared via the in situ higher cuprate formation-conjugate addition reaction. This method proved to be convenient and stereospecific. The standard cuprate method, involving an organocuprate reagent generated from an isolated vinyl iodide, did not work well in our case and gave a complicated mixture of products. The target compound will be submitted for assessment of bio log ical activity.

The regulation of oat coleoptile phosphoenolpyruvate carboxylase and malic enzyme by Hâ ½ and metabolites : kinetic evidence for and against a cytosolic pH-stat

Phosphoenolpyruvate carboxylase (PEPC) and malic enzyme activities in soluble protein extracts of Avena coleoptiles were investigated to determine whether their kinetics were consistent with a role in cytosol pH regulation. Malic enzyme activity was specific for NADP+ and Mn2+. Maximal labelled product formation from [14C]-substrates required the presence of all coenzymes, cofactors and substrates. Plots of rate versus malate concentration, and linear transformations there- 2 of, indicated typical Michaelis-Menten kinetics at non-saturating malate levels and substrate inhibition at higher malate levels. pH increases between 6.5 and 7.25 increased near-optimal activity, decreased the degree of substrate inhibition and the Kmapp(Mn2+) but did not affect the Vmax or Kmapp(malate). Transformed data of PEPC activity demonstrated non-linear plots indicative of non-Michaelian kinetics. pH increases between 7.0 and 7.6 increased the Vmax and decreased the Km app (Mg2+) but did not affect the Kmapp(PEP). Various carboxylic acids and phosphorylated sugars inhibited PEPC and malic enzyme activities, and these effects decreased with pH increases. Metabolite inhibited malic enzyme activity was non-competitive and resulted mainly from Mn2+ chelation. In contrast, metabolite inhibited PEPC activity was unique for each compound tested, being variously dependent on the PEP concentration and the pH employed. These results indicate that fluctuations in pH and metabolite levels affect PEPC and malic enzyme activities similarly and that 3 the in vitro properties of PEPC are consistent with its proposed role in a pH-stat, whereas the in vitro properties of the malic enzyme cannot be interpreted in terms of a role in pH regulation.

Stereoselective synthesis of substituted hexahydro-3a,4a-diazacyclopentaphenanthren-4-ones and aminoferrocenes

This thesis explored the development of several methodologies for the stereoselective construction of ligand frameworks and some of their applications. The first segment concerns the application of an enantioselective lithiation at an Sp3_ hybridized position adjacent to nitrogen by means of the widely used and typically highly effective enantioselective lithiation with ( -)-sparteine. This investigation was intended to develop a method to install chirality into a system that would be converted into a family of diaminoylidenes for use as phosphine mimics in transition metal catalysis or as nucleophilic reagents. Molecular modeling of the system revealed some key interactions between the substrate and (-)-sparteine that provided general insight into the diamine's mode of action and should lend some predictive value to its future applications. The second portion focuses on the development of methods to access 1,2- disubstituted aminoferrocenes, an underexplored class of metallocenes possessing planar chirality. Two routes were examined involving a diastereoselective and an enantioselective pathway, where the latter method made use of the first BF3-mediated lithiation-substitution to install planar chirality. Key derivatives such as 1,2- aminophosphines, made readily accessible by the new route, were evaluated as ligands for Pd(II), Pt(II) and Ir(I). These complexes show activity in a number of transformations with both achiral and prochiral substrates. Optimization experiments were conducted to prepare enantiomerically enriched 2-substituted-I-aminoferrocenes by direct asymmetric lithiation of BF3-coordinated tertiary aminoferrocenes. A predictive computational model describing the transition state of this reaction was developed in collaboration with Professor Travis Dudding's group (Department of Chemistry, Brock University). The predicted stereochemistry of the process was confirmed by single-crystal X-ray analysis of a 2-phosphino-l-dimethylaminoferrocene derivative. Enantiomerically pure samples of the aminophosphine ligands derived from this new process have given promising preliminary results in the enantioselective hydrogenation of prochiral alkenes and warrant further stUdy in metal-mediated catalysis.

Experimental and Computational Studies on Copper and Hydrobenzoin Derivatives in Catalytic Asymmetric Reactions

The use of theory to understand and facilitate catalytic enantioselective organic transformations involving copper and hydrobenzoin derivatives is reported. Section A details the use of theory to predict, facilitate, and understand a copper promoted amino oxygenation reaction reported by Chemler et al. Using Density Functional Theory (DFT), employing the hybrid B3LYP functional and a LanL2DZ/6-31G(d) basis set, the mechanistic details were studied on a N-tosyl-o-allylaniline and a [alpha]-methyl-[gamma]-alkenyl sulfonamide substrate. The results suggest the N-C bond formation proceeds via a cisaminocupration, and not through a radical-type mechanism. Additionally, the origin of diastereoselection observed with [alpha]-methyl-[gamma]-alkenyl sulfonamide arises from avoidance of unfavourable steric interactions between the methyl substituent and the N -protecting group. Section B details the computationally guided, experimental investigation of two hydrobenzoin derivatives as ligands/ catalysts, as well as the attempted synthesis of a third hydrobenzoin derivative. The bis-boronic acid derived from hydrobenzoin was successful as a Lewis acid catalyst in the Bignielli reaction and the Conia ene reaction, but provided only racemic products. The chiral diol derived from hydrobenzoin successfully increased the rate of the addition of diethyl zinc to benzaldehyde in the presence of titanium tetraisopropoxide, however poor enantioinduction was obseverved. Notably, the observed reactivity was successfully predicted by theoretical calculations.

The Political Economy of St. Catharines' Illicit Taxi Trade

The global restructuring of production has led to increasingly precarious working conditions around the world. Post-industrial work is characterized by poor working conditions, low wages, a lack of social protection and political representation and little job security. Unregulated forms of work that are defined as “irregular” or “illegal”, or in some cases “criminal,” are connected to sweeping transformations within the broader regulated (formal) economy. The connection between the formal and informal sectors can more accurately be described as co-optation and, as a subordinate integration of the informal to the formal. The city of St. Catharines within Niagara, along with much of Ontario’s industrial heartland, has been hard hit by deindustrialization. The rise of this illegal service is thus viewed against the backdrop of heavy economic restructuring, as opportunities for work in the manufacturing sector have become sparse. In addition, this research also explores the paradoxical co-optation of the growing illicit taxi economy and consequences for racialized and foreign credentialed labour in the taxi industry. The overall objective of this research is to explore the illicit cab industry as not only inseparable from the formal economy, but dialectically, how it is as an integrated and productive element of the public and private transportation industry. Furthermore the research examines what this co-optation means in the context of a labour market that is split by race.

SYNTHESIS OF CYCLIC AZOBENZENE ANALOGUES FOR INCORPORATION INTO OLIGONUCLEOTIDES, PEPTIDES AND POLYMERS

(A) In recent years, considerable amount of effort has contributed towards enhancing our understanding of the new photoswitch, cyclic azobenzene, particularly from the theoretical point of view. However, the challenging part with this system was poor efficiency of its synthesis from 2,2’- dinitrodibenzyl and lack of effective methods for further modification which would be useful to incorporate this system into biomolecules as a photoswitch. We report the synthesis of cyclic azobenzene and analogues from 2,2’-dinitrodibenzyl, which would allow for further incorporation of this cyclic azobenzene into biomolecules. Reaction of 2,2’-dinitrodibenzyl with zinc metal powder in the presence of triethylammonium formate buffer (pH-9.5) gave a cyclic azoxybenzene, 11,12-dihydrodibenzo[c,g][1,2]diazocine-5-oxide. The latter compound was converted into cyclic azobenzene analogues (bromo-, chloro-, cyano-, and carboxyl) through subsequent transformations. The carboxylic acid analogue was reacted with D-threoninol to give the corresponding amide, which readily undergoes photo-isomerization upon illumination with light. Upon illumination with light at 400 nm, approximately 70% of cis- isomer of amide was isomerized to trans- isomer. It was observed that cis- to trans- isomerization reached the maximum steady state of light transmission after approximately 40 min, whereas the trans- to cis- isomerization approximately acquired in 2 h to regain full recovery of light transmission. Cyclic azobenzene phosphoramidite was synthesized from DMT-protected D-threoninol linked cyclic azobenzene. (B) In recent years, there has been considerable interest invested towards the synthesis of azobenzene analogues for incorporation into proteins. Among the many azobenzene analogues, the synthesis of bi-functional cyclic azobenzene analogues for the incorporation into proteins is relatively new. In this thesis, we report the synthesis of a cyclic azobenzene biscarboxylic acid from 4-(bromomethyl)benzonitrile. (C) Azobenzene has been widely used in the field of polymer science to study the surface morphology and surface properties of polymers. In this thesis, we report the incorporation of cyclic azobenzene into a commercial polymer 2- (hydroxyethyl)methacrylate. Samples collected after 24 h from the reaction solution showed approximately 9% of incorporation of cyclic azobenzene into polymer compared to samples collected after 10 h, which showed approximately 6% incorporation.

3-O-Demethylation of thebaine and the synthesis of a flacourtia aglycone from benzoic acid.

Two synthetic projects were embarked upon, both fraught with protecting group nuance and reaction selectivity. Transformations of the opiate skeleton remain a valuable tool for the development of new medicines. Thebaine, a biosynthetic intermediate in the expression of morphine, was converted in three steps to oripavine through two parallel modes. Through the use of protecting group manipulations, two irreversible scaffold rearrangements were avoided during aryl methyl ether bond cleavage. This chemistry constitutes a new path in manipulations of the morphinan scaffold through protective groups. A new compound family, the flacourtosides, contains an unusual cyclohexenone fragment. The newly described compounds show in preliminary tests antiviral activity against dengue and chikungunya. This aglycone was approached on three pathways, all beginning with the chemoenzymatic dihydroxylation of benzoic acid. A first attempt from a known vinyl epoxide failed to epimerize and cooperate under deprotective conditions. A second and third attempt made use of a diastereoselective dihydroxylation reaction, which was critical in reaching the correct stereochemistry and oxidation state. The methyl ester of the aglycone was prepared, constituting the first synthesis of the non-trivial natural product framework.

Mirroring Enzymes: The Role of H-Bonding In HQuin-BAM Catalyzed Asymmetric Aza-Henry Reactions: A DFT Study into the Reactivity, Mechanism, and Origins of Selectivity

The exact mechanistic understanding of various organocatalytic systems in asymmetric reactions such as Henry and aza-Henry transformations is important for developing and designing new synthetic organocatalysts. The focus of this dissertation will be on the use of density functional theory (DFT) for studying the asymmetric aza-Henry reaction. The first part of the thesis is a detailed mechanistic investigation of a poorly understood chiral bis(amidine) (BAM) Brønsted acid catalyzed aza-Henry reaction between nitromethane and N-Boc phenylaldimine. The catalyst, in addition to acting as a Brønsted base, serves to simultaneously activate both the electrophile and the nucleophile through dual H-bonding during C-C bond formation and is thus essential for both reaction rate and selectivity. Analysis of the H-bonding interactions revealed that there was a strong preference for the formation of a homonuclear positive charge-assisted H-bond, which in turn governed the relative orientation of substrate binding. Attracted by this well-defined mechanistic investigation, the other important aspect of my PhD research addressed a detailed theoretical analysis accounting for the observed selectivity in diastereoselective versions of this reaction. A detailed inspection of the stereodetermining C-C bond forming transition states for monoalkylated nitronate addition to a range of electronically different aldimines, revealed that the origins of stereoselectivity were controlled by a delicate balance of different factors such as steric, orbital interactions, and the extent of distortion in the catalyst and substrates. The structural analysis of different substituted transition states established an interesting dependency on matching the shape and size of the catalyst (host molecule) and substrates (guest molecules) upon binding, both being key factors governing selectivity, in essence, offering an analogy to positive cooperative binding effect of catalytic enzymes and substrates in Nature. In addition, both intra-molecular (intra-host) and inter-molecular (host-guest, guest-guest) stabilizing interactions play a key role to the high π-facial selectivity. The application of dispersion-corrected functionals (i.e., ωB97X-D and B3LYP-D3) was essential for accurately modeling these stabilizing interactions, indicating the importance of dispersion effects in enantioselectivity. As a brief prelude to more extensive future studies, the influence of a triflate counterion on both reactivity and selectivity in this reaction was also addressed.

High-Spin and Emissive Molecular Materials: Synthesis and Characterization of New Polynuclear Ni(II) Complexes from the Use of Aromatic Schiff Bases as Bridging Ligands

The employment of the bridging/chelating Schiff bases, N-salicylidene-4-methyl-o-aminophenol (samphH2) and N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH2), in nickel cluster chemistry has afforded eight polynuclear Ni(II) complexes with new structural motifs, interesting magnetic and optical properties, and unexpected organic ligand transformations. In the present thesis, Chapter 1 deals with all the fundamental aspects of polynuclear metal complexes, molecular magnetism and optics, while research results are reported in Chapters 2 and 3. In the first project (Chapter 2), I investigated the coordination chemistry of the organic chelating/bridging ligand, N-salicylidene-4-methyl-o-aminophenol (samphH2). The general NiII/tBuCO2-/samphH2 reaction system afforded two new tetranuclear NiII clusters, namely [Ni4(samph)4(EtOH)4] (1) and [Ni4(samph)4(DMF)2] (2), with different structural motifs. Complex 1 possessed a cubane core while in complex 2 the four NiII ions were located at the four vertices of a defective dicubane. The nature of the organic solvent was found to be of pivotal importance, leading to compounds with the same nuclearity, but different structural topologies and magnetic properties. The second project, the results of which are summarized in Chapter 3, included the systematic study of a new optically-active Schiff base ligand, N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH2), in NiII cluster chemistry. Various reactions between NiX2 (X- = inorganic anions) and nacbH2 were performed under basic conditions to yield six new polynuclear NiII complexes, namely (NHEt3)[Ni12(nacb)12(H2O)4](ClO4) (3), (NHEt3)2[Ni5(nacb)4(L)(LH)2(MeOH)] (4), [Ni5(OH)2(nacb)4(DMF)4] (5), [Ni5(OMe)Cl(nacb)4(MeOH)3(MeCN)] (6), (NHEt3)2[Ni6(OH)2(nacb)6(H2O)4] (7), and [Ni6(nacb)6(H2O)3(MeOH)6] (8). The nature of the solvent, the inorganic anion, X-, and the organic base were all found to be of critical importance, leading to products with different structural topologies and nuclearities (i.e., {Ni5}, {Ni6} and {Ni12}). Magnetic studies on all synthesized complexes revealed an overall ferromagnetic behavior for complexes 4 and 8, with the remaining complexes being dominated by antiferromagnetic exchange interactions. In order to assess the optical efficiency of the organic ligand when bound to the metal centers, photoluminescence studies were performed on all synthesized compounds. Complexes 4 and 5 show strong emission in the visible region of the electromagnetic spectrum. Finally, the ligand nacbH2 allowed for some unexpected organic transformations to occur; for instance, the pentanuclear compound 5 comprises both nacb2- groups and a new organic chelate, namely the anion of 5-chloro-2-[(3-hydroxy-4-oxo-1,4-dihydronaphthalen-1-yl)amino]benzoic acid. In the last section of this thesis, an attempt to compare the NiII cluster chemistry of the N-naphthalidene-2-amino-5-chlorobenzoic acid ligand with that of the structurally similar but less bulky, N-salicylidene-2-amino-5-chlorobenzoic acid (sacbH2), was made.

What Is a Commody? Two Axiomatic Anwers

We identify conditions under which preferences over sets of consumption opportunities can be reduced to preferences over bundles of \"commodities\". We distinguish ordinal bundles, whose coordinates are defined up to monotone transformations, from cardinal bundles, whose coordinates are defined up to positive linear transformations only.

Finite-Sample Inference Methods for Simultaneous Equations and Models with Unobserved and Generated Regressors

We propose finite sample tests and confidence sets for models with unobserved and generated regressors as well as various models estimated by instrumental variables methods. The validity of the procedures is unaffected by the presence of identification problems or \"weak instruments\", so no detection of such problems is required. We study two distinct approaches for various models considered by Pagan (1984). The first one is an instrument substitution method which generalizes an approach proposed by Anderson and Rubin (1949) and Fuller (1987) for different (although related) problems, while the second one is based on splitting the sample. The instrument substitution method uses the instruments directly, instead of generated regressors, in order to test hypotheses about the \"structural parameters\" of interest and build confidence sets. The second approach relies on \"generated regressors\", which allows a gain in degrees of freedom, and a sample split technique. For inference about general possibly nonlinear transformations of model parameters, projection techniques are proposed. A distributional theory is obtained under the assumptions of Gaussian errors and strictly exogenous regressors. We show that the various tests and confidence sets proposed are (locally) \"asymptotically valid\" under much weaker assumptions. The properties of the tests proposed are examined in simulation experiments. In general, they outperform the usual asymptotic inference methods in terms of both reliability and power. Finally, the techniques suggested are applied to a model of Tobin’s q and to a model of academic performance.

Projection-Based Statistical Inference in Linear Structural Models with Possibly Weak Instruments

It is well known that standard asymptotic theory is not valid or is extremely unreliable in models with identification problems or weak instruments [Dufour (1997, Econometrica), Staiger and Stock (1997, Econometrica), Wang and Zivot (1998, Econometrica), Stock and Wright (2000, Econometrica), Dufour and Jasiak (2001, International Economic Review)]. One possible way out consists here in using a variant of the Anderson-Rubin (1949, Ann. Math. Stat.) procedure. The latter, however, allows one to build exact tests and confidence sets only for the full vector of the coefficients of the endogenous explanatory variables in a structural equation, which in general does not allow for individual coefficients. This problem may in principle be overcome by using projection techniques [Dufour (1997, Econometrica), Dufour and Jasiak (2001, International Economic Review)]. AR-types are emphasized because they are robust to both weak instruments and instrument exclusion. However, these techniques can be implemented only by using costly numerical techniques. In this paper, we provide a complete analytic solution to the problem of building projection-based confidence sets from Anderson-Rubin-type confidence sets. The latter involves the geometric properties of “quadrics” and can be viewed as an extension of usual confidence intervals and ellipsoids. Only least squares techniques are required for building the confidence intervals. We also study by simulation how “conservative” projection-based confidence sets are. Finally, we illustrate the methods proposed by applying them to three different examples: the relationship between trade and growth in a cross-section of countries, returns to education, and a study of production functions in the U.S. economy.

Lecture sociodémographique de l'évolution de la mortalité par suicide au Québec (1926-2004): la question de l'âge et des générations.

Depuis deux siècles, les transformations les plus remarquables du phénomène du suicide concernent la relation avec la variable âge. En effet, le suicide a longtemps progressé avec l'âge pour culminer à la vieillesse, mais le dernier quart de siècle au Québec a vu ce rapport modifié, suggérant qu'il s'agit désormais d'un phénomène de jeunes. Notre étude examine les tendances récentes de l'évolution de la mortalité par suicide au Québec du point de vue de l'âge, discute des effets respectifs possibles de l'âge, de la période et de la génération de 1926 à 2004 et offre des pistes d'interprétation sociologique. Nous présentons dans un premier temps les transformations de la société québécoise depuis 1930 ainsi qu'un bilan synthétique des connaissances sur le suicide au Québec par rapport aux tendances internationales, ceci du point de vue de différentes variables sociodémographiques. Notre étude rappelle ensuite les grandes théories et idées sur le suicide, de la littérature classique aux réflexions contemporaines. On y remarque que la variable âge est rarement au coeur de ces conceptions, mais plutôt en marge de celles-ci, médiatisées par d'autres variables sociales. Les résultats de notre analyse montrent la présence d'un net effet de génération dans l'évolution de la mortalité masculine due au suicide au Québec. Ce phénomène n'est pas présent chez les femmes. Les générations récentes adoptent toutefois un comportement différent de celles des baby-boomers et il sera intéressant de suivre leur trajectoire dans l'avenir.