Acylhydrazone-based dynamic combinatorial libraries : study of the thermodynamic / kinetic evolution , configurational and coordination dynamics

Resumo The kinetic and thermodynamic selectivity of acylhydrazone formation in dynamic combinatorial libraries N7JLM is describedó Jompetition reactions were generated from hydrazidesO isoniazidé çánitroábenzohydrazideé çádimethylaminoábenzohydrazideé and nicotinic hydrazide as well as the aldehyde derivativesO benzaldehyde and Éápyridineá carboxaldehydeó The obtained species and the distribution of the 7JLs were monitored by qUáNMR spectroscopy finding that those acylhydrazones containing the çá dimethylaminoábenzohydrazide moiety are both the kinetic and thermodynamic product of their respective librariesó Jonfigurational and coordination dynamics for some of these libraries were also investigatedó The obtained results allowed the study of the redistribution of components and the amplification of one or more products using light and metal ions as physical and chemical templatesé respectivelyó Se describe la selectividad cinética y termodinámica de la formación de acilá hidrazona en bibliotecas combinatorias dinámicas N7JLMó Se generaron reacciones competitivas a partir de hidrazidasO isoniazidaé çánitroábenzohidrazidaé çá dimetilaminoábenzohidrazida y hidrazida nicotínica3 así como a partir de los derivados de aldehídoO benzaldehído y Éápiridiná carboxaldehidoó Las especies obtenidas y la distribución de los 7JLs fueron monitoreados mediante espectroscopia qUá NMRé encontrándose que las aciláhidrazonas que contenían la çádimetilaminoá benzohidrazida son tanto el producto cinéticoé como el termodinámico de sus respectivas bibliotecasó También se investigaron las dinámicas de configuración y de coordinación para algunas de estas bibliotecasó Los resultados obtenidos permitieron estudiar la redistribución de los componentes y la amplificación de uno o más productos usando luz e iones metálicos como plantillas físicas y químicasé respectivamenteó É descrita a seletividade cinética e termodinâmica da formação de acilá hidrazonas em livrarias combinatórias dinâmicas N7LJMó Qoram geradas reações competitivas a partir das hidrazidasO isoniazidaé çánitroábenzohidrazidaé çá dimetilaminoábenzohidrazida e hidrazida nicotínica3 além dos derivados de aldeídoO benzaldeído e Éápiridinácarboxaldeídoó 6s espécies obtidas e a distribuição dos 7LJs foram monitorados mediante espectroscopia qUáNMRé foi encontrado que as acilá hidrazonas que continham à çádimetilaminoá benzohidrazida são tanto o produto cinético como o termodinâmico de suas respectivas livrariasó Também investigaramáse as dinâmicas de configuração e coordenação para algumas destas livrariasó Os resultados obtidos permitem estudar a redistribuicao dos componentes e a amplificação de um ou mais produtos usando luz e íons metálicos como modelos físicos e químicosé respectivamenteó

The kinetic and thermodynamic selectivity of acylhydrazone formation in dynamic combinatorial libraries N7JLM is describedó Jompetition reactions were generated from hydrazidesO isoniazidé çánitroábenzohydrazideé çádimethylaminoábenzohydrazideé and nicotinic hydrazide as well as the aldehyde derivativesO benzaldehyde and Éápyridineá carboxaldehydeó The obtained species and the distribution of the 7JLs were monitored by q UáNMR spectroscopy finding that those acylhydrazones containing the çá dimethylaminoábenzohydrazide moiety are both the kinetic and thermodynamic product of their respective librariesó Jonfigurational and coordination dynamics for some of these libraries were also investigatedó The obtained results allowed the study of the redistribution of components and the amplification of one or more products using light and metal ions as physical and chemical templatesé respectivelyó Se describe la selectividad cinética y termodinámica de la formación de acilá hidrazona en bibliotecas combinatorias dinámicas N7JLMó Se generaron reacciones competitivas a partir de hidrazidasO isoniazidaé çánitroábenzohidrazidaé çá dimetilaminoábenzohidrazida y hidrazida nicotínica3 así como a partir de los derivados de aldehídoO benzaldehído y Éápiridiná carboxaldehidoó Las especies obtenidas y la distribución de los 7JLs fueron monitoreados mediante espectroscopia q Uá NMRé encontrándose que las aciláhidrazonas que contenían la çádimetilaminoá benzohidrazida son tanto el producto cinéticoé como el termodinámico de sus respectivas bibliotecasó También se investigaron las dinámicas de configuración y de coordinación para algunas de estas bibliotecasó Los resultados obtenidos permitieron estudiar la redistribución de los componentes y la amplificación de uno o más productos usando luz e iones metálicos como plantillas físicas y químicasé respectivamenteó É descrita a seletividade cinética e termodinâmica da formação de acilá hidrazonas em livrarias combinatórias dinâmicas N7LJMó Qoram geradas reações competitivas a partir das hidrazidasO isoniazidaé çánitroábenzohidrazidaé çá dimetilaminoábenzohidrazida e hidrazida nicotínica3 além dos derivados de aldeídoO benzaldeído e Éápiridinácarboxaldeídoó 6s espécies obtidas e a distribuição dos 7LJs foram monitorados mediante espectroscopia q UáNMRé foi encontrado que as acilá hidrazonas que continham à çádimetilaminoá benzohidrazida são tanto o produto cinético como o termodinâmico de suas respectivas livrariasó Também investigaramáse as dinâmicas de configuração e coordenação para algumas destas livrariasó Os resultados obtidos permitem estudar a redistribuicao dos componentes e a amplificação de um ou mais produtos usando luz e íons metálicos como modelos físicos e químicosé respectivamenteó Figure 1.Formation of a DCL from "building blocks" and the addition of a template, which causes amplification of the member forming the more stable complex.

Introduction
Dynamic combinatorial chemistry RDCCk is a powerful tool to study and create complex chemical systems in a relative simple manner7 DCC was defined by Sanders as molecular or supramolecular combinatorial chemistry under thermodynamic control R1k7 When a system is formed by molecular fragments that can react with each otherU combining themU a mixture of many compounds that interconverts constantlyU will be obtainedU i7e7 building blocks are connected together by reversible bonds which are continuously forming and breaking in the reaction medium RFigure xk7 This product mixture is known as Dynamic Combinatorial Library RDCLk7 The system is reversible and it is in equilibriumU thusU any external effect could shift this equilibrium7 ó cleanVcut example of these systems and relating Emil Fisher's concept is placing a template in the systemU which fits precisely with one member of the libraryU and subsequently amplify or shift the equilibrium towards the formation of a product R2k7 Materials and methods DCC and DCLMs have been widely used for the synthesis and identification of small molecular receptors R3-7k7 These tools have also helped to generate effective ligands for biomacromolecules and biosensors R8-10kU synthesis of catalysts R11-13kU crosslinked materials R14-16kU capsules and cages R17-19kU selfVreplication R20kU nanomachines R21kU among others7 Yased on previous work done by Lehn's group R22-24kU we have chosen a set of four hydrazides and two aldehydes as building blocks in order to generate several dynamic combinatorial libraries7 These building blocks were selected since the acylhydrazonesU which can be formedU have a number of characteristics that make them attractive for DCLMs formation; ik unlike the hydrazonesU the acylhydrazones have a much weaker double bond making them favorable to perform exchange reactionsO iik these compounds have an imino double bondU which has been widely investigated in our research group and it is known that is sensitive to light R25-26kO iiik some of these compounds have coordination sites in their chemical structure that serve as tridentate ligand to coordinate to cation metals7 Having in mind these characteristicsU we have analyzed how the distributions of the formed libraries vary by the presence of the metals and UV light as external stimuli7 For this purposeU nuclear magnetic resonance technique was used as a tool for monitoring the evolution of the dynamic library7 One eq of aldehyde A-B was added to an ethanol solution Rq7D mLk of the corresponding hidrazide 1-4 Rx eqk with q7D μL of glacial acetic acid7 The mixture was heated under reflux of ethanol for F to E h7 The resulting precipitate was collected by vacuum filtration and recrystallized from cold ethanol to afford the pure acylhydrazones in their EVconfiguration7

Standard procedure for the preparation of DCLs
The DCLs were prepared by mixing in a sealed NMR tube Runder inert atmosphere of N W U done in a óldrich ótmosYagk x eq of the corresponding aldehydes RWWq μLk and acylhydrazines RWWq μLk in DMSOVd 6 or CD F OD at Wq °C7 The starting time of reaction Rt 2 Dk was considered as the time in which the solution of aldehydes was poured into the NMR tube and entered in contact with the hydrazines solution7 x HVNMR spectroscopy was used as a tool to monitor the evolution of the library7 For those experiments involving UV radiationU a WqD W mercury lamp was used as an UV source7 The NMR tube was irradiated while pouring the reagentsO in a second experiment the NMR tube with the compounds was allowed to equillibrate during WL h7 ófterwardsU the tube was irradiated during x h7 For the addition of metal ionsU solutions of the corresponding M WB ion were standarized by atomic absorption spectroscopy calculating the concentration in a calibration curve7 When mixing aldehydes and hydrazines redacción; a large number of x HVNMR signals are obtained making difficult to identify the products7 ThereforeU each possible acylhydrazoneU as part of the libraryU was synthesized from each corresponding hydrazide and aldehyde derivativesU according to a methodology reported previously R22k RFigure Wk7 The reactions were monitored by thin layer chromatography RTLCkU and the spectroscopic data were consistent with the proposed structures RE configurationk of compounds A-1 to B-4 RFigure Fk7 Details of the synthesis were described in the Materials and methods section7 The synthesis was performed with the aim to identify characteristic signals in the x HVNMR spectra of each acylhydrazone7 Signals found in the region between xx7q and xW7q ppmU which correspond to the NVH protons Ras determined by WD NMR techniqueskU were chosen to determine the distribution of the products on the libraries Rsee Characterization data for acylhydrazonesk and further confirmed by DOSY experiments to corroborate the asignment of the NVH proton signals7   Characterization data for acylhydrazones

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Benzaldehyde nicotinoyl hydrazone CB-4ES Using the method described aboveN the compound was synthesized and obtained in a /41 yield6 M6p6S 8FDO8T4°C6 Elemental analysis calcd6 C1E for C 8T H 88 N T OS CN KD6TFJ HN I6DFJ NN 8=6KKJ foundS CN K/6I/J HN I6DIJ NN 8/6K=6 FTOIR CKBrE ν;cm O8 TF/4 CNOHEN 8KRT CC=OEN 8RR4 CC=NE6 Two competitive reactionsR named DCLF1 and DCLF2R were carried out from the hydrazides 1F4 and aldehyde A qDCLF1k or B qDCLF2k by mixing equimolar amounts of the respective building blocks in a NMR tube and using a deuterated solvent qFigure 2kH The libraries with A and B were monitored for 326 min by 1 HFNMR spectroscopyR further time did not showed any changes in the relative concentration of the DCLH The relative amount of acylhydrazone formed was calculated from the relative intensities of the corresponding signals and compared to an internal standart q1R4FdioxanekH As shown in Figure 4 for DCLF1 and Figure 5 for DCLF2R the appearance of four new signals in the aforementioned region shows the formation of the four corresponding acylhydrazones qA-1R A-2R A-3 and A-4kH Competitive reactions of acylhydrazines 1-4 with aldehydes A and B Figure 4. 1 H-NMR spectra at three selcted (aleatorially) times of the DCL-1 formed by 1-4 and A in DMSO-d 6 .
From the NMR dataR kinetic traces for acylhydrazones formation were plotedH AditionallyR equillibrium distributions of the different acylhydrazones are shown in Figure 6H From these resultsR it is observed that A-3 and B-3 are the acylhydrazones kinetically and thermodynamically favored in their respective DCLsH The latter is understood based on the greater nucleophilicity of acylhydrazine 3H LikewiseR the highest rate of formation and stability of A-3 and B-3 may also be explained if we consider that the precursors of the other acylhydrazones have in their structure either one electron withdrawing group or an electronegative nitrogen in the aromatic ringR which by both inductive and resonance effects generate an electronic deficiency in the moleculeR making it less reactive towards the nucleophilic attack of the nitrogen to the carbonyl group of the aldehyde q2kH

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While in A-3 and B-36 the dimethylamine group makes the molecule more electronHrich6 thus confering a higher reactivity for the nucleophilic attack6 which is reflected in the greater proportion and the greater stability of this acylhydrazonesN Although equillibrium was confirmed by a control experiment using different starting concentrations of previously prepared acylhydrazones reaching the same final distributions6 it is important to remark that those distributions are reached in longer times which implies a slow amine interchange in the DCLN Despite that amine interchange can be increased by changing the nature of the solvent6 this was not considered in this study to avoid issues with the solubility of the reagentsN

DCL-3: hydrazides 1-4 plus aldehydes A and B
Aldehydes A-B were added to an equimolar mixture of hydrazides 1-4N The reaction was monitored for 8F7 min6 resulting in F68 F HH NMR spectra in total Tsome of them are shown in Figure 78N Figure 8 shows the kinetic trace of the competition DCL reactionN According to the results6 A-3 is the kinetic product6 not only for the larger nucleophilicity of acylhydrazine 3 but also for the larger electrophilicity of aldehyde A6 which plays an important role in the reaction kineticsN Likewise6 acylhydrazones formed from A were found in larger amounts than the ones formed from BN This can be attributed to the electronegative nitrogen present in A2 which by inductive effect causes the carbonyl group to be more electron deficient2 making it more susceptible to nucleophilic attackU Noteworthy2 data fit to a kinetic model is quite difficult for this system2 however2 within the first O% of the reaction2 the DCL follows a second order reaction with a MIW% error2 this allows to estimate that acylhydrazone A-3 is generated in around H=Ifold faster than its B-3 counterpartU Interestingly2 electrophilicity of the aldehyde is more important than acylhydrazine nucleophilicity in both2 kinetic and thermodynamic control of the DCLU Upon equilibrium2 AIcontaining acylhydrazones exhibit similar concentrations2 which supports the dynamic character of the DCLU The evident acylhydrazine interchange is probably due to the conjugation of the hydrazonic nitrogen LINHI4 with the carbonyl group which reduces the conjugation of this one with the imino group LC=N42 making the latter a more reactive bond towards nucleophiles such as hydrazides or water L274U Therefore2 the exchange reaction promotes another product to be formed at the expense of A-32 but still2 at the end of the experiment Lt = OHF min42 this acylhydrazone continues to be the one with the highest percentage yield2 therefore A-3 is the thermodynamic product in the libraryU The difference between the greater proportion of acylhydrazones formed from A2 as compared with the generated from B2 confirms the higher reactivity of =Ipyridinecarboxaldehyde over benzaldehyde2 due to the presence of an electronegative nitrogen atom in the ringU

Effect of UV light irradiation
Acylhydrazones formed from the aldehyde A exhibit2 in the Z configuration2 a thermodynamic stabilization by the formation of an intramolecular hydrogen bond between the amine hydrogen and the pyridine nitrogen upon photochemical isomerizationU Meanwhile2 the Z configuration of acylhydrazones from B do not exhibit this thermodynamic stabilization L25, 264U With this in mind2 it was interesting to observe the effect of UV light irradiation on the acylhydrazone distribution of the DCLsU For this purpose2 the library was formed only with hydrazides 1 and 4 as well as the aldehydes A and B2 due to their solubility in MeOHId 4 U The latter was used instead of DMSOId 6 because photoisomerization experiments in DMSOId 6 did not exhibit any appreciable changes2 even after HWj min of UV irradiation2 contrary to MeOHId 4 LFigure S4U This contrasting result is due to the viscosity of DMSO which slows down the photoisomerization of hydrazoneI based compounds L25-284U In a typical procedure2 a competition reaction was carried out until equillibrium was reachedU Afterwards2 the mixture was irradiated with UV light using a mercury lamp of =Wj WU The competition reaction was monitored for ==O minU The relative concentrations of each acylhydrazone were calculated only at the end of the experiment and the results were 7SxHWx=SxHF% of A-1xA-4x B-1xB-42 respectivelyU The fact that those products containing the hydrazide 1 are in greater proportion2 suggests that hydrazide 4 is less nucleophilic by the overall inductive effect that the N of the pyridine ring in position 7 has on the R groupU Once the equilibrium was reached2 the library was subjected to UV irradiation for H h and then was monitored by H HINMRU It is remarkable the appearance of new signals in the spectra shown in Figures HjIH= which correspond to the Z isomers of compounds A-1 and A-4U The relative percentages shown in Table H were calculated by integrating those signals obtained in Figure HH that are not overlapped and then by the substraction between these and the overlapped ones2 the integrals and therefore the percentages of the latters were obtainedU From the distribution of acylhydrazones it can be observed that the product which is amplified after Vj min of UV light irradiation is the Z isomer of A-12 suggesting the adaptation of the library when a stimulus is appliedU Vantomme et al.L274 also observed the same photoselection in a different DCL with similar yields of photoisomerizationU A second DCL was generated from the same building blocks Lacylhydrazines 1 and 2 and aldehydes A and B4 in the presence of UV light irradiationU For this purpose2 the NMR tubes were irradiated with a mercury vapor lamp during H h before the reaction startedU Afterwards2 the H HINMR spectra were taken to observe the distribution of the library LFigure H74U The amplified product for this DCL was the acylhydrazone B-1 LTable H4U The presence of A-1 and A-4 Z isomers on the library proved that UV light is part of the system2 however2 this also indicates that whether UV light is added at the beginning or at the end of the reaction2 the amplified product will be a different oneU

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NoteworthyC in both cases the resulting product distribution is quite difficult to analyze even by the use of OD NMR experimentsC besidesC once the UV light is removed the products concentrations do not go back to the previous distributionsF These results imply that the system is in a metastable thermodynamic point due to the hydrogen bond formation V22, 25kF In any caseC these experiments proved the use of UV light as an irreversible template in DCL amplification and deserves further explorationF

Effect of the introduction of metal cations on DCL distributions
FinallyC we wanted to explore the role of metal ions on DCL distributionsC since it is well known that hydrazones and acylhydrazones derived from OLpyridinecarboxaldehydes and OL pyridinehydrazines or acylhydrazines are able to coordinate metal cations in a terpyrdineLlike fashion V22, 25, 26kF In this regard it can be thought that the introduction of metal ions can be used as a template to amplify acylhydrazones derived from aldehyde AF AccordinglyC hydrazines 1 and 4 and aldehydes A y B were used to form the DCL; in additionC ;F4 eq of ZnVOTfk O were added to the mixtureC the reaction was monitored for WO; minF Comparing this library with other DCL in the present work VFigure Z1k it was observed from the beginning of the reaction the apearence of only four NLH signals instead of eight corresponding to the formation of every possible acylhydrazoneF The ones that disappearC correspond to those acylhydrazones derived from aldehyde AC those which have a propitious structure to form a complex with Zn OI by their tridentate NNO coordination site V28-32kF These signals disappearance are proof of the formation of ML O type complexes usually formed with this kind of ligands V22, 25-27kF When they form a complexC these ligands are deprotonatedC either because there is a relatively basic environment or because the enol form of the ligand predominates V32kF Although it is known that the addition of this template VM OI ionsk results in the formation of such complexesC it is not possible to know which component is amplifiedC because the signals from each product are highly overlappedF ThereforeC it is necessary to determine the binding and stability constants to have a clearer idea of what it is inside the solutionF Although DCLs have been studied with some detail over the last yearsC it is difficult to compare our results with the literatureF SinceC on one handC most reports deal with the use of biological chemical templates and only one article introduces UV light to a DCL Vbased on aldehydes and hydrazinesk obtaining similar results V27kF On the other handC metal ion selection has been studied for a more simple system V23k and similar to the present work a metalloselection was observedF üeneration of dynamic combinatorial libraries derived from acylhydrazines 1-4 and aldehydes A and B were monitored by U éL NMR spectroscopyC achieving the calculation of the products distribution in time in most cases= The acylhydrazone A-3 was both the kinetic and thermodynamic product of two of the formed librariesC confirming the greater nucleophilicity of the corresponding hydrazide due to the electron releasing character of the dimethylamino group and the higher electrophilicity of VLpyridinL carboxaldehyde as compared with benzaldehydeC because of the presence of an electronegative nitrogen atom in its structure= In competitive B8L reactions acylhydrazone products derived from hydrazide 1 2versus hydrazide 4x were found in higher yieldsC suggesting that the reduced nucleophilicity of hydrazide 4 is due to the overall inductive effect that the pyridine ring N in position F has on the R group 2RKL28OxLNéLNé V x= 7xposure to a physical stimulus such as irradiation with UV lightC demostrated that B8Ls respond or adapt themselves to that stimulusC reorganizing and leading to the formation of a new library= In this particular caseC it was also observed that depending on the time when the stimulus is addedC the amplified product changeC because the formation of the E isomer occurs first that the Z oneC still in the presence of UV light= _inallyC the disappearance of the signals corresponding to the acylhydrazones Né V fragment derived from VL pyridinecarboxaldehydeC by adding Zn VD C demostrates the formation of ML V type complexes and its amplification= Conclusions /uthors are grateful to Vicerrectoría de Investigaciones and 8entro de 7xcelencia en Nuevos Materiales 287NMx from Universidad del Valle 28olombiax for the financial support of this project= We also thank professor Julien Wist for his collaboration regarding NMR spectroscopy experiments= FNpyridinecarboxaldehyde nicotinoyl hydrazone °A-4CS Using the method described aboveH the compound was synthesized and obtained in a D;M yieldO MOpOS ;I=N;R7°CO Elemental analysis calcdO °MC for C ;F H ;7 N I OS CH ATO/;J HH IOIAJ NH FIO/AJ foundS CH R=OATJ HH IO/IJ NH FFO=;O FTNIR °ATRC ν6cm N; TI/I °NNHCH ;AA=°CBOCH ;RDT °CBNCO ; HNNMR °I77 MHzH DMSONd6C δ ;FOFI °sH ; HCH DO7= °dH J B ;ORA HzH ; HCH =O=F-=O/R °mH ; HCH =OAT °dH J B IOA= HzH ; HCH =OIA °sH ; HCH =OF= °dH J B /O=7 HzH ; HCH =O77 °dH J B /O=7 HzH ; HCH /ODI-/O=A °mH ; HCH /ORD °ddH J B /O=7H IO== HzH ; HCH /OI=-/OI7 °mH ; HCO ;T CN NMR °;77OA7 MHzH DMSONd6C δ ;AFO;FH ;RTO;7H ;RFOA;H ;IDO/7H ;I=O/RH ;I=O/TH ;T/O;TH ;TRO/TH ;FDO7RH ;FIO/AH ;FTO=TH ;F7OF7O Benzaldehyde isonicotinoyl hydrazone °B-1CS Using the method described aboveH the compound was synthesized and obtained in a /;M yieldO MOpOS ;D=N;DD°CO Elemental analysis calcdO °MC for C ;T H ;; N T OS CH ADOTFJ HH IODFJ NH ;=OAAJ foundS CH A=O/TJ HH IO=DJ NH ;=OT=O FTNIR °KBrC ν6cm N; TIRR °NNHCH ;ADF °CBOCH ;RAA °CBNCO ; HNNMR °I77 MHzH DMSONd6C δ ;FO;; °sH ; HCH =O/D °dH J IO;7 HzH F HCH =OIA °sH ; HCH /O=T °dH J TOD7 HzH F HCH /O/=-/O/I °mH F HCH /OI/ °brO sOH T HCO ;T CNNMR °;77OA7 MHzH DMSONdAC δ ;A;OARH ;R7OTTH ;IDO7/H ;I7OI/H ;TIO7;H ;T7OI;H ;F=OD7H ;F/OF/H ;F;ORTO Benzaldehyde pNnitrobenzoyl hydrazone °B-2CS Using the method described aboveH the compound BNF was obtained with a /DM yieldO MOpOS FA7NFAF°CO Elemental analysis calcdO °MC for C ;I H ;; N T O T S CH AFOIRJ HH IO;FJ NH ;ROA;J foundS CH A;OARJ HH IO;RJ NH ;ROTRO FTNIR °KBrC ν6cm N; TIR7 °NNHCH ;ARA °CBOCH ;RRI °CBNCO ; HNNMR °I77 MHzH DMSONd6C δ ;FO;/ °sH ; HCH =OI/ °sH ; HCH =OT/ °dH J =ORD HzH F HCH =O;R °dH J =O/= HzH F HCH /O/=-/O/T °mH F HCH /OID-/OIR °mH T HCO

Figure 8 .
Figure 8. Kinetic trace of relative product formation over time of the library DCL-3.

Figure 9 .
Figure 9.A portion of 1 H-NMR k400 MHz, DMSO-d 6 U spectrum at t = 817 min and the assignment of signals.

Figure 10 .
Figure 10.A portion of the 1 H-NMR k400 MHz, MeOH-d 4 U spectra of acylhydrazones A-1 ktopU and A-4 kbottomU taken at different times under UV irradiation.

Figure 12 .
Figure 12.A portion of 1 H-NMR b400 MHz, MeOH-d 4 ´spectrum after irradiation with UV light.

Figure 11 .
Figure 11.A portion of the 1 H-NMR spectra of the DCL-1 after 1h of irradiation in MeOH-d 4 .

Table 1 .
Relative percent of products observed in two DCL´s Figure 13.A portion of the 1 H-NMR spectra of the DCL in MeOH-d 4 irradiated with UV light at the beginning of reaction.Figure 14.A portion of the 1 H-NMR spectra of the library formed from four hydrazides, both aldehydes and Zn 2+ , in DMSO-d 6 and the spectrum of DCL-3.