molecules Article Isonicotinamide-Based Compounds: From Cocrystal to Polymer Francisco Sánchez-Férez 1 , Daniel Ejarque 1 , Teresa Calvet 2 , Mercè Font-Bardia 3 and Josefina Pons 1, * 1 Departament de Química, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; francisco.sanchez.ferez@uab.cat (F.S.-F.); daniel.ejarque@e-campus.uab.cat (D.E.) 2 Cristal·lografia, Mineralogia i Dipòsits Minerals, Universitat de Barcelona, 08028 Barcelona, Spain; mtcalvet@ub.edu 3 Unitat de Difracció de Raig-X, Centres Científics i Tecnològics de la Universitat de Barcelona (CCiYUB), Universitat de Barcelona, 08028 Barcelona, Spain; mercef@ccit.ub.edu * Correspondence: josefina.pons@uab.cat (J.P.); Tel.: +34-935-812-895  Received: 2 November 2019; Accepted: 15 November 2019; Published: 17 November 2019  Abstract: The reaction between [Cu(µ-OAc)(µ-Pip)(MeOH)]2 (1) (OAc = acetate; Pip = 1,3-benzodioxole- 5-carboxylate) and isonicotinamide (Isn) in MeOH as solvent yielded two mixture pairs of three compounds: {(HPip)2 (Isn) (2), [Cu(Pip)2 (Isn)2 ] (3)} and {(3), {[Cu3 (Pip)2 (OAc)2 (µ-Isn)2 (Isn)2 (µ- OCH3 )2 (MeOH)2 ]·2MeOH}n (4)}. Modifying the reaction conditions (t, T, molar ratio), 2 and 3 have been successfully isolated, whereas 3 and 4 had to be mechanically separated. The recrystallization of 3 in pentanol yielded single crystals of compound [Cu(Pip)2 (Isn)2 ]·C5 H11 OH (3a). The X-ray crystal structure of 2, 3a, and 4 has been elucidated showing a cocrystal, a monomer, and an unusual coordination polymer, respectively. The Pip ligand exhibited a chelate (3a) or a monodentate (4) coordination mode, but the Isonicotinamide (Isn) ligand is the one that promoted the arrangement of different structures and also mainly directs the formation of the 2D and 3D supramolecular assemblies. All the structures have been analyzed by Hirshfeld surface. In addition, the energy frameworks and lattice energy values of 2 and 3a have been calculated. Keywords: cocrystal; Cu(II) compounds; isonicotinamide; amide–amide pattern; coordination polymer 1. Introduction The design of new organic and inorganic materials linked by intermolecular forces is a topic of current interest as models for biological systems and in materials science [1,2]. In this sense, hydrogen bonds are the main directing motif and are raised as one of the strongest and most used tools for crystal engineering [3,4]. Their large electrostatic components facilitate its ordering as first suggested by Etter’s rules—the best hydrogen bond donor will associate with the best hydrogen bond acceptor [5] and subsequently superseded by supramolecular suitable directing motifs (synthons), which imply functional groups [6,7]. Synthons are the backbone to design novel structures based on hierarchical, and therefore predictable, associations of the parts involved in them. Above all, carboxylic acids can form strong hydrogen bonds through their acidic moiety, which in combination with N-containing groups (amines, amides, or pyridines) are replaced by the corresponding N-H···O interactions. The strength of this association is governed by the acidic and basic character of both parties involved in it [8]. This has led to the formation of single and multi-component crystals made of organic molecules named cocrystals [9]. The importance of cocrystals lies in the possibility to modify the physical properties of their components (melting point, solubility, or conductivity, among Molecules 2019, 24, 4169; doi:10.3390/molecules24224169 www.mdpi.com/journal/molecules Molecules 2019, 24, 4169 2 of 18 others) while keeping their chemical properties unaltered. This goal is achieved by the rearrangement of the intermolecular interactions promoted by the components and, thus, the formation of a new crystal structure [10,11]. It should be noted that during the formation of these assemblies, and in presence of a metal ion, the Isonicotinamide (Isn) units can interact either with the acidic moiety or with the metal center, wherefore a competition with the final complex formation occurs [12,13]. Among all the possible coformers, Isn stands out from the rest for its potential acceptor ability and therefore, it is considered a valuable component in the formation of cocrystals [14]. The Isn synthon itself promotes the amide···amide hydrogen bond interaction, ordering in a linear fashion but pointing in opposite direction. The pKa rule allows to ascertain if the combination of the selected acid and base will form a salt or a cocrystal. If ∆pKa < 0, the carboxylic acid···pyridine (O–H···N) interaction will be neutral [15,16]. For this reason, 1,3-benzodioxole-5-carboxylic acid (HPip, pKa = 4.35) has raised as a prospective candidate, owing to the fact that it obeys this rule and, thus, should form cocrystals with Isn (pKb = 10.87). Besides, Isn formed numerous coordination complexes promoting their assembly in supramolecular structures mainly directed by the amide···amide pattern, even in competitive interactions with additional directing motifs [17–20]. In turn, carboxylates have a large versatility of coordination modes and can be used as a building block including Isn [21,22]. Among them, Cu(II) nodes possess high affinity toward oxygen donor atoms, especially belonging to carboxylate motifs and formed thousands of complexes. For this reason, metal carboxylates have been raised as one of the major interesting research items concerning their structural versatility and labile nature [23,24]. Previously, our group evinced the solvent-dependent formation of five Cu(II) compounds—one monomer and four dimers—resulting from the reaction between [Cu(µ-OAc)(µ-Pip)(MeOH)]2 (1) and Isn in different solvents. It should be noted that, in all of them, the Pip ligands were displaced, and only acetate ligands remained coordinated [25]. As a continuation, in this contribution we have assayed the reactions between 1 and Isn in order to synthesize compounds containing both Pip and Isn ligands in their structures. With this aim, we have modified the reaction conditions (reaction time, temperature, concentration, etc.). This made it possible to isolate three compounds: one cocrystal ((HPip)2 (Isn), 2), one Cu(II) monomer ([Cu(Pip)2 (Isn)2 ], 3), and a Cu(II) coordination polymer ({[Cu3 (Pip)2 (OAc)2 (µ-Isn)2 (Isn)2 (µ-OCH3 )2 (MeOH)2 ]·2MeOH}n , 4) (Scheme 1). Compound 3 was recrystallized in pentanol yielding [Cu(Pip)2 (Isn)2 ]·C5 H11 OH (3a). Hirshfeld surfaces analysis as well as Energy frameworks and Lattice energy calculations facilitated the better understanding of the Isn role in these systems. 2. Results and Discussion 2.1. Synthesis and Characterization of Cocrystal 2 The reaction of 1 [26,27] with Isn in MeOH as solvent at room temperature (r.t.) for 2h yielded a mixture of compounds (HPip)2 (Isn) (2) and [Cu(Pip)2 (Isn)2 ] (3). Otherwise, when the reaction was performed under reflux, only compound 3 was obtained. Following this, compound 2 was isolated by crystallizing a mixture of HPip:Isn (2:1 molar ratio) in MeOH at r.t. In this work, the reactions were performed without adding acetic acid, and the experimental conditions (t, T or concentration) have been modified in order to incorporate the Pip units in the structure of the complexes [28]. Compound 2 was characterized by EA, FTIR-ATR, 1 H- and 13 C{1 H}-NMR spectroscopies, and single crystal X-ray diffraction method. The FTIR-ATR and 1 H- and 13 C{1 H}-NMR spectra in dmso-d6 solution displays the characteristic bands of the two molecules (Figures S1–S3). In the FTIR-ATR spectrum (Figure S1a), the ν(N-H) bands appear at 3321 and 3140 cm−1 and are shifted with respect to the free Isn (3359 and 3179 cm−1 , respectively) (Figure S1b). There is a broad signal at 1680 cm−1 , assigned to the ν(C=O)Isn and ν(COOH)HPip , which is also shifted compared to the HPip- (Figure S1c) and Isn-free molecules (1667 and 1655 cm−1 , respectively). Molecules 2019, 24, 4169 3 of 18 Additional Molecules 2019, peaks 24, x FORcan PEERbe identified as δ(O=CN), δip (C-H) and δoop (C-H) [29]. The REVIEW 1 H- and 3 of 18 13 C{1 H}-NMR spectra show no displacement of the bands respect to the free molecules. The H-NMR 1 Additional peaks can be identified as δ(O=CN), δip(C-H) and δoop(C-H) [29]. The 1H- and 13C{1H}- spectrum confirms the 2:1 proportion of the coformers (Figures S2 and S3). NMR spectra show no displacement of the bands respect to the free molecules. The 1H-NMR Therefore, the EA, FTIR-ATR, and 1 H- and 13 C{1 H}-NMR data are in agreement with the structures spectrum confirms the 2:1 proportion of the coformers (Figures S2-S3). determined by singlethe Therefore, crystal EA, X-ray diffraction FTIR-ATR, method. and 1H- The and 13C{ ∆pKa (pK 1H}-NMR a conjugate data acid of pyridine—pK are in agreement with the a carboxylic acid)) structures betweenbythe determined parties single which crystal X-rayform the association diffraction method. The is ΔpKa determining a (pKa conjugate factor acid offor the formation of a salta or pyridine—pK a cocrystal. carboxylic acid)) If ∆pKa the between < 0 parties or ∆pKawhich> 3.75, formathe cocrystal or aissalt association will be formed, a determining respectively. If 0 < ∆pKa < 3.75, there is an intermediate interaction, and either cocrystal or factor for the formation of a salt or a cocrystal. If ΔpKa < 0 or ΔpKa > 3.75, a cocrystal or a salt will saltbecan be formed, found [16]. respectively. If 0 < ΔpK a < 3.75, there is an intermediate interaction, and either cocrystal or salt can be found [16]. Scheme Scheme 1. 1. Outlineof Outline ofthe the synthesis synthesis ofofcompounds compounds2–4.2–4. 2.2. Crystal 2.2. Crystal Structure Structure of Compound of Compound 22 Compound Compound 2 crystallizes 2 crystallizes in in thethe triclinicP1 triclinic P1 space space group. group.ItsItscrystal structure crystal can be structure candescribed as be described as the sum of the interactions between its functional groups. The position and nature of each the sum of the interactions between its functional groups. The position and nature of each functionality functionality generates the particular interactions, which dictate the crystal arrangement [4,29]. The generates the particular interactions, which dictate the crystal arrangement [4,29]. The association of association of HPip and Isn leads to the formation of a cocrystal [30], in which there is not any HPip and Isn homomericleads to the formation interaction of a cocrystal and therefore, [30], has the assembly in which grownthere is not mixing any homomeric molecules. interaction In this kind of and therefore, the assembly multi-component hasor solids, salts grown mixing cocrystals molecules. can be In this on formed depending kind of multi-component where the proton is locatedsolids, salts or cocrystals can be formed depending on where the proton is located and hence the drift in the bond distances of the parties involved. In this case, the C=O, C-N and C-O distances of Isn and HPip molecules have been analyzed and compared with the values from the anionic Pip ligand present in Molecules 2019, 24, 4169 4 of 18 the complexes, which suggested for both of them a neutral charge (Table 1). In addition, the ∆pKa between both, the conjugated acid of Isn (pKa = 3.61), and HPip (pKa = 4.35) has a value of −0.74 and thus, they are prospective candidates for generate a cocrystal [16]. Table 1. Comparative of bond lengths (C=O, C-N, C-N) between cocrystal and monomer and polymer compounds. 2 3a 4 BSM A BSM B Bond Length (Å) Distance (Å) Bond Length (Å) Bond Distance (Å) C=OIsn 1.253(4) 1.241(5) C=OIsn 1.236(2) C=OIsn coord 1.234(4) C=OHPip ···Npy 1.233(4) 1.226(4) C=OPip 1.281(3) C=OIsn 1.240(5) C=OHPip ···H-Namide 1.217(5) 1.228(5) C=OPip 1.250(3) C=OPip 1.330(5) C-N 1.321(4) 1.326(4) C-N 1.328(3) C=OPip 1.317(6) C-OHHPip ···Npy 1.300(5) 1.314(4) C-NIsn coord 1.276(6) C-OHHPip ···H-Namide 1.324(4) 1.318(4) C-N 1.257(5) Selected distances are highlighted in bold. The basic structural motifs (BSMs) [31], also called long-range synthon Aufbau modules (LSAMs), are two crystallographically independent trimeric large synthons (A and B) constructed by three subunits—two HPip and one Isn. These BSMs are fastened through basic molecules (BSMs) [32]. Those are two small synthons: a type III dimeric square motif (N-HIsn ···O=CHPip ; O-HHPip ···O=C-N-HIsn ) and a type I dimeric chain motif (O-H···NIsn ) with distances similar to other reported cocrystals (Table 2) (Figure 1a). In contrast, type II motifs (amide···amide) are not present, probably induced by the MeOH solvent, which is polar enough to break this interaction [33]. Moreover, Isn molecule holds together two adjacent HPip units, from contiguous BSMs, via the remaining amidic Hanti and the Hortho and Hmeta from opposite sides. Protons at the same flank merge with the same oxygen atom of the carbonyl, while the Hortho pyridil interacts with the protonated oxygen atom of other HPip molecule (Table 2) (Figure 1b). Table 2. Supramolecular interactions present in compound 2. Intra-BSM A H···A (Å) D···A (Å) D-H (Å) >D-H···A (◦ ) O6-H6O···N2 1.916 2.611 0.840 139.37 N1-H1A···O1 1.979 2.840 0.881 165.44 O2-H2O···O5 1.835 2.645 0.840 161.52 Intra-BSM B O6A-H6AA···N2A 1.778 2.615 0.841 173.73 N1A-H1AA···O1A 1.969 2.831 0.881 166.02 O2A-H2OA···O5A 1.819 2.634 0.840 163.11 Inter-BSM A N1-H1B···O7A 2.033 2.880 0.880 161.48 C14-H14···O7A 2.342 3.279 0.950 168.81 C12-H12···O2A 2.374 3.099 0.950 132.81 Inter-BSM B N1A-H1AB···O7 2.031 2.879 0.880 161.40 C13A-H13A···O2 2.376 3.097 0.950 132.40 C11A-H11A···O7 2.344 3.281 0.950 168.84 Molecules 2019, 24, x FOR PEER REVIEW 5 of 18 Molecules 2019, 24, 4169 5 of 18 Molecules 2019, 24, x FOR PEER REVIEW 5 of 18 Figure 1.1. Basic Figure Basic molecules molecules (BSMs) composed by two HPip HPip and and one one Isn Isn subunits subunits (left, (left, A; A; right, right, B) B) Figure 1. Basic molecules (BSMs) composed by two HPip and one Isn subunits (left, A; right, B) presentinin present compound compound 2. interactions 2. (a) (a) interactions forming forming the trimeric the trimeric BSM BSM (A, B). (b) (A, B). (b) Intermolecular Intermolecular interactions present in compound 2. (a) interactions forming the trimeric BSM (A, B). (b) Intermolecular between the BSMs. interactions between the BSMs. interactions between the BSMs. BSMs BSMs are aredisposed BSMs disposed along along are disposed the alongthe(1 001/2) (1(1 the 1/2)and 01/2) and(1/2 and (1/20003/4) (1/2 planes 3/4)planes 3/4) planes(A (A (A andand andB,B, B, respectively), andand respectively), respectively), eacheach and one one each one of them of them associates associates of them with with associates a closely a closely with packed a closelypacked α-helix packedα-helix shape (Figure shape (Figure α-helix shape 2a). (Figure2a).2a). These These These chains chains chains are are are joined joined joined via the via the via the central central Isn Isnunits, central units, which which Isn units, forms forms which 2D forms grid 2D2Dgrid gridshape shapelayers shape layersparallel layers parallelto parallel theacacac totothe the plane plane plane (Figure (Figure (Figure 2b). 2b).2b). Figure 2. (a) α-helix shape through the assembly of A and B chains. (b) b axis view of the 2D layers along the ac plane. Figure2.2.(a) Figure α-helixshape (a)α-helix shapethrough through thetheassembly ofAAand assembly of andBBchains. (b) bbaxis chains. (b) axisview viewof ofthe the2D 2Dlayers layers along theac the acplane. 2.3. Synthesis along and Characterization of the Coordination Complexes 3 and 4 plane. 2.3. The andsynthesis of [Cu(Pip) (Isn)Coordination ofof2the 2] (3) and {[Cu3(Pip)2(OAc)2(μ-Isn)2(Isn)2(μ-OCH3)2(MeOH)2] 33and 44 2.3. Synthesis Synthesis 2MeOH}nand Characterization Characterization (4) was performed mixing the 1Coordination Complexes and Isn in a 1:7Complexes molar ratio andwith MeOH as solvent and under The refluxsynthesis conditions of [Cu(Pip) for a week. 2 (Isn) In these 2 ] (3) and {[Cu conditions, The synthesis of [Cu(Pip)2(Isn)2] (3) and {[Cu3(Pip)2(OAc)2(μ-Isn) (Pip) both 3 (OAc) compounds 2 2 (µ-Isn) 2 (Isn) simultaneously 2 (µ-OCH 2(Isn) 3 )32)(MeOH) crystallized 2(μ-OCH in a 22]] 2(MeOH) 2MeOH} 2MeOH} (4) was performed 1.5:1n proportion (violet (3) andmixinggreen 1 and Isn in aand (4) crystals) 1:7they molar wereratio with MeOH mechanically n (4) was performed mixing 1 and Isn in a 1:7 molar ratio with MeOH as solvent and under as solvent separated. Compound and under reflux 3conditions was successfully for a isolated week. In under these reflux conditions conditions, both and modifying compounds the compoundcrystallized simultaneously 1:Isn (1:2) molar in a 1.5:1 reflux conditions for a week. In these conditions, both compounds simultaneously crystallized in a ratio. proportion Compound (violet (3) 3 andwas recrystallized green (4) in crystals) a MeOH/pentanol and they were (1:1) mixture mechanically yielding single separated. crystals Compound of 3 1.5:1 compound proportion[Cu(Pip)(violet 2(3) and (Isn) green (4) crystals) and they were mechanically separated. Compound 2]·C5H11OH (3a). Unfortunately, 4 could not be obtained as a pure product was successfully 3 waschanging successfully isolated isolated under reflux under reflux conditions and conditions modifying the compound 1:Isn (1:2) molar ratio. the reaction conditions. Compounds 3 and 4and weremodifying characterized thebycompound EA, FTIR-ATR, 1:Isnand (1:2) UV-molar Compound ratio.Vis Compound 3 was recrystallized 3 was in a recrystallized MeOH/pentanol (1:1) mixture yielding single crystals of compound spectroscopies. The violet crystals in of 3a from MeOH/pentanol the mixture were(1:1) mixture yielding characterized by EA and single FTIR-ATR crystals of [Cu(Pip) compound 2 (Isn) 2 ]·C5 H211 [Cu(Pip) OH2]·C (Isn) (3a). Unfortunately, 4 could not be obtained as a pure product changing 5H11OH (3a). Unfortunately, 4 could not be obtained as a pure product the reaction changing theconditions. Compounds reaction conditions. Compounds 3 and 43were and 4characterized were characterized by EA, by FTIR-ATR, EA, FTIR-ATR, and and UV-Vis UV- spectroscopies. The violet crystals of 3 from the mixture were characterized Vis spectroscopies. The violet crystals of 3 from the mixture were characterized by EA and FTIR-ATR by EA and FTIR-ATR spectroscopies, while single crystals of 3a were characterized by FTIR-ATR spectroscopy. Complex 4 Molecules 2019, 24, 4169 6 of 18 Molecules 2019, 24, x FOR PEER REVIEW 6 of 18 unavoidably suffers a loss of the occluded MeOH molecules after manipulations required for the EA. spectroscopies, In addition, while single the structure of 3a crystals and 4 was of 3aelucidated were characterized by single bycrystal FTIR-ATR spectroscopy. X-ray diffractionComplex method.4 The FTIR-ATR spectra of compounds 3–4 (Figures S4–S6) display two pairs of bands atthe unavoidably suffers a loss of the occluded MeOH molecules after manipulations required for EA.cm−1 1557 In addition,−1 the structure of 3a and −1 4 was elucidated by −1 single crystal X-ray diffraction method. (3) and 1602 cm (4) and at 1435 cm (3) and 1387 cm (4) assigned to [νas (COO)] and [νs (COO)], The FTIR-ATR spectra of compounds 3–4 (Figures S4–S6) display two pairs of bands at 1557 cm−1 respectively, from the carboxylate groups. The difference between these bands (∆ = νas (COO) − (3) and 1602 cm−1 (4) and at 1435 cm−1 (3) and 1387 cm−1 (4) assigned to [νas(COO)] and [νs(COO)], νs (COO)) [34] is 121 respectively, from (3)theand 215 (4), attributable carboxylate groups. Thetodifference a chelatebetween and a monodentate these bands (Δ coordination = νas(COO) mode, - respectively. The ν(C=O) band is present at 1694 cm −1 in compound 3, while in 4, it is split in two at νs(COO)) [34] is 121 (3) Isnand 215 (4), attributable to a chelate and a monodentate coordination mode, 1696 and 1631 cmThe−1 , which suggests the presence of two different Isn 3, ligands. respectively. ν(C=O)Isn band is present at 1694 cm−1 in compound while inLikewise, 4, it is splitthe in [δ(O=CN)] two at vibrational mode −1 (3) and at 627 and 582 cm−1 (4). Additional bands as ν(N-H), 1696 and 1631iscm identified −1 at 629 cm , which suggests the presence of two different Isn ligands. Likewise, the [δ(O=CN)] vibrational δip (C-H) and δoopmode(C-H)is identified are alsoatassigned 629 cm−1 (3) (seeand exp.at 627 and 582[28]. section) cm−1If(4).the Additional FTIR-ATR bandsof as3 isν(N-H), compared δ (C-H) and δ (C-H) are also assigned (see exp. section) [28]. If the FTIR-ATR to 3a, the unique difference arises in the solvent region in which the alcohol group of the pentanol ip oop of 3 is compared to 3a, the unique difference arises in the solvent region in which the molecule promoted the formation of broader bands overlapped with those deriving from the amino alcohol group of the pentanol molecule promoted the formation of broader bands overlapped with those deriving from the amino group (Figure S5). group (Figure S5). The electronic spectra of compounds 3 and 4 have been recorded in MeOH as solvent. All spectra The electronic spectra of compounds 3 and 4 have 9been recorded in MeOH as solvent. All spectra 2 showshow one band in the one band visible in the region, visible region, characteristic characteristicof of dd9 Cu(II) Cu(II)complexes complexes which which is assigned is assigned to theto 2the Eg Eg → T→2 2g electronic transition 2T2g electronic transition (Figure (Figure S7)S7)[35]. [35].Compound Compound 33 has its λλmax has its maxatat713 713nmnm (ε (ε = 77 = 77 −1 M−1M× cm×−1cm ), −1 ), nm (ε ==404 −1 −1 whilewhile 4 displayed this this 4 displayed d–dd–d electronic electronictransition transition single singleband bandatat706 706 nm 404MM−1 × cm× cm−1). The). high ε The high ε valuevalue of 4 respect to 3 could of 4 respect be explained to 3 could be explained by the larger by the number larger number of Cu(II) of Cu(II)centers centers ininthe thepolymeric polymericarray. array. 2.4. Crystal and Extended Structure of Compound 3a 2.4. Crystal and Extended Structure of Compound 3a Compound 3a crystallizes in the triclinic P1 space group. It has a monomeric structure with a [CuO4 NCompound 3a crystallizes in the triclinic P1 space group. It has a monomeric structure with a 2 ] core that is composed by two pairs of Pip and Isn ligands (Figure 3). The average twist [CuO4N2] core that is composed by two pairs of Pip and Isn ligands (Figure 3). The average twist angle angle (ata) is a useful tool to differentiate between a trigonal prismatic and an octahedral geometry but (ata) is a useful tool to differentiate between a trigonal prismatic and an octahedral geometry but it it must be noted that ata value does not give information about how much the geometry is deviated. must be noted that ata value ◦ does not give information about how much the geometry is deviated. If◦ If thisthis value value is iscloser closertoto6060°the the geometry will be geometry will beoctahedral octahedralwhile whileforfor values values proximate proximate to 0°tothe 0 the geometry probe to be trigonal prismatic [36,37]. geometry probe to be trigonal prismatic [36,37]. Figure Figure 3. 3.Molecular Molecular structure structure of ofcompound compound3a.3a. Thevalue The ata ata value forfor thiscomplex this complex is 60◦being is 60° beingthethe three torsion three angles: torsion O2-Cg1-Cg2-O1, angles: −79.26◦ ; −79.26°; N1- O2-Cg1-Cg2-O1, Cg1-Cg2-O2, −46.55 N1-Cg1-Cg2-O2, −46.55°◦ and and O1-Cg1-Cg2-N1, O1-Cg1-Cg2-N1,−54.19°. −54.19This six six ◦ . This coordinated Cu(II) coordinated ion has Cu(II) ion ahas distorted a distorted octahedral geometry with two chelate Pip units and two monodentate Isn ligands. The axial positions octahedral geometry with two chelate Pip units and two monodentate Isn ligands. The axial positions of the octahedron are occupied by the oxygen chelate atoms with the longer Cu-O distance at of the octahedron are occupied by the oxygen chelate atoms with the longer Cu-O distance at 2.5069(16) 2.5069(16) Å, which is usually exhibited 9 by d9 Cu(II) ions due to the Jahn-Teller effect [38,39], while Å, which is usually exhibited by d Cu(II) ions due to the Jahn-Teller effect [38,39], while the remaining oxygen atoms of the chelate Pip units and the nitrogen atoms of the Isn ligands sets the equatorial plane (Table 3). The chelate coordination mode of the Pip ligands promotes the distortion of the octahedral Molecules 2019, 24, 4169 7 of 18 geometry resulting in angles ranging from 57.69(6)◦ to 122.31(6)◦ , and the metal node is out of the equatorial plane (0.522 Å) toward the apical site. Table 3. Selected bond lengths (Å) and bond angles (◦ ) for compound 3a. Molecules 2019, 24, x FOR PEER REVIEW 7 of 18 Bond Length (Å) the remaining oxygen atoms of the chelate Pip units and the nitrogen atoms of the Isn ligands sets Cu(1)-O(1)#1 1.9673(14) Cu(1)-N(1)#1 1.9988(16) the equatorial plane (Table 3). The chelate coordination mode of the Pip ligands promotes the Cu(1)-O(2) 2.5069(16) Cu···Cu 8.023to 122.31(6)°, and the distortion of the octahedral geometry resulting in angles ranging from 57.69(6)° metal node is out of the equatorial plane (0.522 BondÅ) toward Angles ◦ ( ) the apical site. O(1)#1-Cu(1)-O(1) 180 O(2)-Cu(1)-O(1) 57.69(6) Table 3. Selected bond lengths (Å) and bond angles (°) for compound 3a. O(1)#1-Cu(1)-N(1) 89.88(6) O(2)-Cu(1)-O(1)#2 122.31(6) Bond Length (Å) O(1)-Cu(1)-N(1) Cu(1)-O(1)#1 90.12(6) 1.9673(14) N(1)-Cu(1)-O(2) Cu(1)-N(1)#1 91.26(6) 1.9988(16) Cu(1)-O(2) N(1)-Cu(1)-N(1)#1 2.5069(16) 180 Cu···Cu N(1)-Cu(1)-O(2)#1 8.023 88.74(6) Bond Angles (ᵒ) O(2)-Cu(1)-O(2)#1 O(1)#1-Cu(1)-O(1) 180 180 O(2)-Cu(1)-O(1) 57.69(6) #1: −x, −y +89.88(6) O(1)#1-Cu(1)-N(1) 1, −z + 1; O(2)-Cu(1)-O(1)#2 #2: −x, 1 − y, 1 − z. 122.31(6) O(1)-Cu(1)-N(1) 90.12(6) N(1)-Cu(1)-O(2) 91.26(6) N(1)-Cu(1)-N(1)#1 180 N(1)-Cu(1)-O(2)#1 88.74(6) The monomeric units O(2)-Cu(1)-O(2)#1 of 3a are held together 180 via two double hydrogen bond interactions (Table 4). The main pair of interactions is the #1:Isn···Isn −x, −y + 1, pattern; the,1 amide −z + 1; #2: −x − y, 1 − z.moieties engage in a head-to-head disposition, with carbonyl and amide groups pointing in opposite directions. This cooperation expands The through the structure monomeric theunits [110]ofdirection 3a are held together forming 1Dviachains. two double hydrogen The other bond set of interactions interactions are(Table promoted 4). The main pair of interactions is the Isn···Isn pattern; the amide moieties engage in a head-to-head by the furthest coordinated carboxylate oxygen atom of the Pip units that interacts with both hydrogen disposition, with carbonyl and amide groups pointing in opposite directions. This cooperation atoms from the same side of the Isn ligand throughout the [100] direction: one belongs to the amine expands the structure through the [110] direction forming 1D chains. The other set of interactions are moiety (N2-H2B···O2), promoted and the by the furthest other derives coordinated from oxygen carboxylate the aromatic atom ofC-H themeta (C12-H12···O2) Pip units (Figure that interacts with 4a). Theseboth twohydrogen groups of interactions form 2D layers along the ab plane (Figure 4b). atoms from the same side of the Isn ligand throughout the [100] direction: one belongs to the amine moiety (N2-H2B···O2), and the other derives from the aromatic C-Hmeta (C12-H12···O2) Table (Figure 4a). These two 4. Selected groups intermolecular of interactions interactions form 2D for the layers along compound ab plane3a. (Figure 4b). 3b H···A Table 4. Selected (Å) D···Ainteractions intermolecular (Å) D-Hfor(Å) >D-H···A (◦ ) compound 3a. N2-H2A···O5 2.013 2.887 0.880 172.27 3b H···A (Å) D···A (Å) D-H (Å) >D-H···A (ᵒ) N2-H2B···O2 N2-H2A···O5 1.986 2.013 2.842 2.887 0.880 172.27 164.42 0.880 N2-H2B···O2 1.986 2.842 0.880 164.42 C12-H12···O2 2.330 3.251 0.950 163.28 C12-H12···O2 2.330 3.251 0.950 163.28 Figure Figure 4. Representation 4. (a) (a) Representationofofthe theintermolecular intermolecular interactions interactionspromoted promoted by by 3a.3a. Only carboxylate Only carboxylate group of Pip units are shown for clarity. (b) View of the 2D nets generated by the Isn···Isn Isn···Pip group of Pip units are shown for clarity. (b) View of the 2D nets generated by the Isn···Isn and and Isn···Pip interactions along the ab plane. interactions along the ab plane. Molecules 2019, 24, 4169 8 of 18 Molecules 2019, 24, x FOR PEER REVIEW 8 of 18 2.5. Crystal and Extended Structure of Compound 4 2.5. Crystal and Extended Structure of Compound 4 Compound 4 crystallizes in the triclinic P1 space group. It presents a 1D polymeric structure Compound composed 4 crystallizes of alternated in theand monomeric triclinic P1 units, dimeric spacewhich group.expands It presents a 1D the through polymeric structure [1 11] direction composed of alternated monomeric and dimeric units, which expands through (Figure 5a). In this polymer, there are three Cu(II) centers with different arrays and coordination the [1 11] direction (Figure 5a). Indisplaying this polymer,boththere [CuOare three Cu(II) centers with different arrays and coordination environments, 4 N2 ] and [CuO4 N] cores. The first one pertains to monomeric environments, displaying both [CuO 4N2] and [CuO4N] cores. The first one pertains to monomeric units, in which the O atoms belong from two acetate and two MeOH molecules while the N atoms units, from derive in which the ligands two Isn O atoms(Figure belong5b). from In two acetatecore, the second and the twoOMeOH atoms molecules stem from while the N atoms one monodentate derive from two Isn ligands (Figure 5b). In the second core, the O atoms stem Pip unit, two methoxy and one carbonyl group from an Isn unit. The remaining N atoms pertain to from one monodentate Pipdifferent two unit, twoIsn methoxy ligands.and one methoxy These carbonyl groups group from frameantheIsndimeric unit. The remaining unit via a µ2 -ηN1 -O atoms pertain to coordination two different mode Isn The (Figure 5c). ligands. These linkage methoxy of the monomeric groups andframe the units dimeric dimeric for unit via a μ2-ղ growth, the polymeric 1-O coordination results mode (Figure 5c). The linkage of1the 1 monomeric and dimeric units for the polymeric from the bidentate bridging µ2 -η -η -N, O coordination mode of the Isn ligand. It simultaneously growth, results from the bidentate coordinates bridging Cu(II) to the monomeric μ2-η1-ηion 1-N, O coordination mode of the Isn ligand. It simultaneously by the pyridyl N atom and held together via coordination of coordinates the carbonyl O to the monomeric Cu(II) ion by the pyridyl N atom and held together via coordination of Isn atom to one Cu(II) center of the dimeric unit. the carbonyl OIsn atom to one Cu(II) center of the dimeric unit. Figure5.5. Molecular Figure Molecular structure structure of compound 4. (a)(a)Polymeric Polymeric1D 1Dchain chainalong alongthe the[1[111] 11]direction. In direction. Indetail, detail,aaview viewofof(b) (b)monomeric monomeric units units and and (c) dimeric units of of the the polymeric polymericarray. array.Hydrogen Hydrogenatoms atoms areomitted are omittedfor forclarity. clarity. All Allthe thelengths lengthsand andangles angles(Table (Table5)5)are areininrange rangeofofother othercarboxylate carboxylateandandpyridil-containing pyridil-containing Cu(II) Cu(II) compounds [20]. These dimeric units display a distorted square pyramidal geometrywith compounds [20]. These dimeric units display a distorted square pyramidal geometry withaaττ value valueofof0.03 0.03[40]. [40].The Thehindered hindereddisposition dispositionofofthe thecarbonyl carbonylOO IsnIsnatom atomininthe thedimeric dimericarrays arraysforces forcesthe the geometry 1 1 coordination modes of the methoxy geometryatatthetheapical apicalposition. position.AtAtthe thesame sametime, time,thetheµ2μ-η 2-ղ-O-O coordination modes of the methoxy groups groupsdrift driftthe theequatorial equatorialangles anglesand andpromote promoteits itsdeviation deviationfrom fromthetheperfect perfectsquare squarepyramid pyramid(the(the apical-equatorial ◦ ◦ apical-equatorialangles anglesrange rangefrom from84.80(10) 84.80(10)°toto104.73(10) 104.73(10)°).). TheTheIsnIsnmolecule moleculehas hasa amore morebasic basicpK pKbb value value(10.87) respect (10.87) to other respect to common pyridine derivatives other common pyridine (2-benzylpyridine, 5.13; 3-phenylpyridine, derivatives (2-benzylpyridine, 5.13; 3- 4.8; 4-acetylpyridine, phenylpyridine, 4.8;3.51), which can promote 4-acetylpyridine, 3.51), the formation which of methoxide can promote molecules that the formation drive the of methoxide molecules that drive the arrangement of the polymeric array. The additional reflux period in combination with the basic pKb of the Isn ligand could drive the MeOH groups deprotonation, and their consequent coordination to the Cu(II) ions in 4. Molecules 2019, 24, 4169 9 of 18 arrangement of the polymeric array. The additional reflux period in combination with the basic pKb of the Isn ligand could drive the MeOH groups deprotonation, and their consequent coordination to the Cu(II) ions in 4. Molecules 2019, 24, x FOR PEER REVIEW 9 of 18 Table 5. Selected bond lengths (Å) and bond angles (◦ ) for compound 4. A further consideration is a large Cu···O bond Bond length Length (Å)of 2.672 Å, which would provide a pseudo- octahedral geometry to the Cu(II) Cu(1A)-O(6A) center of the dimeric 1.936(3) unit. This distance between Cu(1B)-N(1B)#1 the metal ion and 2.006(3) the uncoordinated Cu(1A)-O(1A) carboxylate oxygen atom of the Pip unit 1.957(3) seems to be too long Cu(1B)-O(2W) to be considered as 2.546(3) a Cu-O bond but Cu(1A)-O(6A)#2 not to the extent of being negligible.Cu(1A)···Cu(1A) 1.957(2) Other reported longer distances have been 3.052(9) Cu(1A)-O(1B) previously taken into consideration, as in2.395(3) Cu(1A)···Cu(1B) the case of catena-(bis(μ-D-Hydrogen10.820(9) malato)-copper(II) Cu(1A)-N(1A) 2.011(3) Cu(1A)···Cu(1B) 9.139(9) dihydrate [41]. Different from most of complexes containing Cu(II) and Isn found in the literature, to Cu(1B)-O(2B)#1 1.964(3) the best of our knowledge, there is only one reference in which Isn synthon avoids the Bond Angles (◦ ) supramolecular amide···amide pattern at expense of the coordination of the amidic oxygen atom [42]. O(6A)-Cu(1A)-O(1A) 167.18(11) O(1A)-Cu(1A)-O(1B) 84.80(10) O(6A)-Cu(1A)-O(6A)#2 76.74(11) O(6A)#2-Cu(1A)-O(1B) Table 5. Selected bond lengths (Å) and bond angles (°) for compound97.61(10) 4. O(1A)-Cu(1A)-O(6A)#2 93.70(11) N(1A)-Cu(1A)-O(1B) 90.83(11) O(6A)-Cu(1A)-N(1A) Bond Length 94.18(12) (Å) O(2B)#1-Cu(1B)-O(2B) 180.00(15) Cu(1A)-O(6A) O(1A)-Cu(1A)-N(1A) 1.936(3) 94.24(12) Cu(1B)-N(1B)#1 O(2B)#1-Cu(1B)-N(1B) 2.006(3) 91.01(12) Cu(1A)-O(1A) O(6A)#2-Cu(1A)-N(1A) 1.957(3) 168.90(12) Cu(1B)-O(2W) O(2B)#1-Cu(1B)-N(1B)#1 2.546(3) 88.99(12) Cu(1A)-O(6A)#2 O(6A)-Cu(1A)-O(1B) 1.957(2) 104.73(10) Cu(1A)···Cu(1A) N(1B)-Cu(1B)-N(1B)#1 3.052(9) 180.0 Cu(1A)-O(1B) O(1B)-Cu(1A)-O(6A) 2.395(3) 104.71(10) Cu(1A)···Cu(1B) O(1B)-Cu(1A)-N(1A) 10.820(9) 90.82(11) Cu(1A)-N(1A) 2.011(3) Cu(1A)···Cu(1B) 9.139(9) #1: −x + 1, −y, −z + 1; #2: −x, −y + 1, −z + 2. Cu(1B)-O(2B)#1 1.964(3) Bond Angles (ᵒ) A further consideration is a large167.18(11) O(6A)-Cu(1A)-O(1A) Cu···O bond length of 2.672 Å, O(1A)-Cu(1A)-O(1B) which would provide 84.80(10) O(6A)-Cu(1A)-O(6A)#2 76.74(11) O(6A)#2-Cu(1A)-O(1B) 97.61(10) a pseudo-octahedral geometry to the Cu(II) center of the dimeric unit. This distance between O(1A)-Cu(1A)-O(6A)#2 93.70(11) N(1A)-Cu(1A)-O(1B) 90.83(11) the metal ion and the uncoordinated carboxylate oxygen atom of the Pip unit seems to be too long O(6A)-Cu(1A)-N(1A) 94.18(12) O(2B)#1-Cu(1B)-O(2B) 180.00(15) to be considered as O(1A)-Cu(1A)-N(1A) a Cu-O bond but not to the extent 94.24(12) of being negligible. O(2B)#1-Cu(1B)-N(1B) Other reported longer 91.01(12) distances have beenO(6A)#2-Cu(1A)-N(1A) previously taken into consideration, 168.90(12) as in the case of catena-(bis(µ-D-Hydrogen O(2B)#1-Cu(1B)-N(1B)#1 88.99(12) O(6A)-Cu(1A)-O(1B) malato)-copper(II) dihydrate [41]. Different104.73(10) from mostN(1B)-Cu(1B)-N(1B)#1 of complexes containing 180.0 Cu(II) and Isn found in O(1B)-Cu(1A)-O(6A) 104.71(10) O(1B)-Cu(1A)-N(1A) 90.82(11) the literature, to the best of our knowledge, there is only one reference in which Isn synthon avoids the #1: −x + 1, −y, −z + 1; #2: −x, −y + 1, −z + 2. supramolecular amide···amide pattern at expense of the coordination of the amidic oxygen atom [42]. The supramolecular structure of 4 is based on the Isn ligand, which acts as a pillar of the expansion The supramolecular structure of 4 is based on the Isn ligand, which acts as a pillar of the joining 1D chains and forming the 3D net (Figure 6). These polymeric chains are non-aligned but expansion joining 1D chains and forming the 3D net (Figure 6). These polymeric chains are non- consecutively disposed in an alternate monomeric-dimeric manner. aligned but consecutively disposed in an alternate monomeric-dimeric manner. Figure 6. Supramolecular 3D expansion of compound 4. The monodentate Isn ligand of the dimeric arrays associate the chains by two hydrogen bond interactions. The mentioned amide···amide pattern holds together dimeric arrays through the b direction (Figure 7a), and this Isn units also participate in the expansion via a double N-Hanti/C- Hortho···O=C interaction with a monodentate Pip unit of other dimeric array in the bc direction. Besides, the carbonyl of this Isn ligand also forms an O···H-C interaction with the occluded MeOH molecule (Figure 7b). The final 3D net is supported by the bidentate bridged Isn linkers, which interact along Molecules 2019, 24, 4169 10 of 18 The monodentate Isn ligand of the dimeric arrays associate the chains by two hydrogen bond interactions. The mentioned amide···amide pattern holds together dimeric arrays through the b direction (Figure 7a), and this Isn units also participate in the expansion via a double N-Hanti /C-Hortho ···O=C interaction with a monodentate Pip unit of other dimeric array in the bc direction. Besides, the carbonyl of this Isn ligand also forms an O···H-C interaction with the occluded MeOH molecule (Figure 7b). The final 3D net is supported by the bidentate bridged Isn linkers, which interact along the a axis by means of their N-Hanti with the non-coordinated carbonyl oxygen atom of the monodentate OAc units pertaining to the monomeric arrays (Table 6) (Figure 7c). Molecules 2019, 24, x FOR PEER REVIEW 10 of 18 Figure Figure7.7.Hydrogen Hydrogenbond bondinteractions interactionspresent presentinincompound compound4.4.(a) (a)Amide-amide Amide-amideassociation associationalong alongthe the bbaxis. axis.(b)(b)N-H N-H anti /C-H anti/C-H ortho···O=C(Pip) ortho interaction ···O=C(Pip) between interaction Isn between and Isn Pip and ligands Pip through ligands the through bc theplane. bc (c) plane. N-H anti ···O=C(OAc) (c) N-H anti ···O=C(OAc)interaction promoted interaction by bridging promoted Isn ligand. by bridging Isn ligand. Selectedintermolecular Table6.6.Selected Table intermolecularinteractions interactionsfor forcompound compound4.4. H···A (Å) H···A (Å) D···A (Å) D-H D···A (Å) D-H >D-H···A (Å)(Å)>D-H···A (ᵒ) (◦ ) N(2B)-H(2BA)···O(6A) 2.14 2.883(4) 0.88 142 N(2B)-H(2BA)···O(6A) 2.14 2.883(4) 0.88 142 O(1W)-H(1W)···O(5A) 1.90 2.739(6) 0.84 173 O(1W)-H(1W)···O(5A) 1.90 2.739(6) 0.84 173 N(2B)-H(2BB)···O(3B) 2.02 2.791(4) 0.88 145 N(2B)-H(2BB)···O(3B) 2.02 2.791(4) 0.88 145 O(2W)-H(2W)···O(3B) 1.86(7) 2.654(5) 0.81(7) 167(7) O(2W)-H(2W)···O(3B) 1.86(7) 2.654(5) 0.81(7) 167(7) N(2A)-H(2AA)···O(5A) 2.04 2.916(5) 0.88 178 N(2A)-H(2AA)···O(5A) 2.04 2.916(5) 0.88 178 N(2A)-H(2AB)···O(2A) 1.92 2.781(5) 0.88 164 N(2A)-H(2AB)···O(2A) 1.92 2.781(5) 0.88 164 2.6. Hirshfeld Surfaces Analysis and Energy Frameworks Calculations 2.6. Hirshfeld Surfaces Analysis and Energy Frameworks Calculations Hirshfeld surfaces analysis of all the structures, energy frameworks and lattice energy Hirshfeld calculations of surfaces complexes analysis 2 andof3aall have the structures, energy frameworks been performed and lattice energy with CrystalExplorer calculations 17.5 [43]. All the of complexes 2 and 3a have been performed with CrystalExplorer 17.5 [43]. All the surfaces surfaces have been calculated at an isovalue of 0.5 e × au−3. The crystal structures of the (HPip)2(Isn) have been calculated −3 of 0.5 eby×energy (2) adduct and 3aat an isovalue have been examined au . The crystal structures framework of the (HPip) based on TONTO, (Isn) (2) adduct using2CE-B3LYP(d,p) and 3a have been examined by energy framework based on TONTO, using CE-B3LYP(d,p) molecular molecular wave-functions, calculated using .cif files obtained from the single crystal X-ray diffraction data. The disorder present in 3a has been identified, and the fractional occupancy has been corrected to 1 in the .cif file. It has not been possible to perform the same calculations with 4 owing to its polymeric structure. Hirshfeld surface, in combination with 2D fingerprint plot, are powerful graphical tools to evaluate intra- and intermolecular interactions present in crystal structures. The surface mapping Molecules 2019, 24, 4169 11 of 18 wave-functions, calculated using .cif files obtained from the single crystal X-ray diffraction data. The disorder present in 3a has been identified, and the fractional occupancy has been corrected to 1 in the .cif file. It has not been possible to perform the same calculations with 4 owing to its polymeric structure. Hirshfeld surface, in combination with 2D fingerprint plot, are powerful graphical tools to evaluate intra- and intermolecular interactions present in crystal structures. The surface mapping facilitates their identification while the fingerprint plot outlines the distances between the atoms involved in these interactions. All these calculations required the generation of the Hirshfeld surface with electron density mapping to construct the wave-function of each selected molecule. Owing to 2 being a multi-component crystal, this surface mapping has been performed for each unique molecule in the unit cell (four HPip and two Isn), verifying that there is one computed wave-function for each unique molecule. Hence, energies were calculated separately for each unique molecule in the unit cell (those from the asymmetric unit), and the energy framework was constructed based on crystal symmetry. In the same way, Hirshfeld surface with electron density mapping and energy calculation of 3a have been performed for each unique molecule in the unit cell (one monomer and one pentanol molecule), and the energy frameworks were constructed based on crystal symmetry. The selection of the appropriate radius for the energy calculation depends on the polarity of the parts involved in the interactions. More polar groups will need a bigger radius, while less polar molecules require a smaller one. Pairwise interaction energies between molecules were computed considering radius of 20.0 Å for 2 and 3a from the centroid of the selected molecule to an atom belonging to its nearest neighbor. Energy framework is a unique tool to visualize the supramolecular architecture of crystal structures. The total energy (Etot ) is divided into electrostatic (Eele ), polarization (Epol ) and dispersion (Edis ) components in which cylinders represent the relative strength of the molecular packing based on a scale factor. The comparison between these components is only possible if the scale factor is the same. For 2 and 3a, the scale factor has been fixed at 240. The main interactions present in compound 2 are identified and highlighted by Hirshfeld surface analysis (Figure S8a). The shape of the 2D fingerprint plot as well as the percentage of surface implied in the interactions suggests a difference between those which held the A and B BSMs (Figure S8b). This data was not sufficiently clear, so a further study including energy calculations was required (vide infra). By comparison, the main interactions and the percentage of surface implied present in compounds 3a and 4 are pinpointed in the Figure S9. In both, the majority involved belongs to the Isn ligand (amide···amide and N-Hanti /C-H···O interactions) and therefore have similar values of surface area implied in them. Energy frameworks of 2 exhibited that the most important energy component is electrostatic (Figure 8a). These attractive forces derive from the amide···acid heterosynthon, while the dispersion energy is comparatively low and is mainly generated by the interaction between HPip units itself (Figure 8b). The total energy framework shows the association of BSMs in pairs that are stacked along the b axis (Figure 8c). The assembly of this cocrystal is dominated by O-H···N and N-H···O hydrogen bonds from the heterosynthons. The strongest associations in both A and B BSMs arise from the amide···acid dimeric square motifs (−68.3 kJ·mol−1 for B and −68.0 kJ·mol−1 for A) with similar but not identical energy values. Followed by the N···H-O chain motifs with energy values of −47.9 kJ·mol−1 (B) and −33.9 kJ·mol−1 (A) (Figure 8d). As suggested by the 2D fingerprint plot with percentage values, there was a difference in the interaction that associates the BSMs. The energy of the N···H-O interaction in A and B presented a difference of ∆EB-A (N···H-O) = 14.0 kJ·mol−1 , which is not negligible and is probably driven by the neighboring interaction in which the carbonyl group participates. These two BSMs are fastened by the central Isn unit, which forms this mentioned C-H/N-H···O double interaction with an acid of the neighboring BSMs with an energy value of −37.4 kJ·mol−1 . Molecules 2019, 24, 4169 12 of 18 Molecules 2019, 24, x FOR PEER REVIEW 12 of 18 Figure 8. Energy Energyframework frameworkdiagram diagram(E(E , E,disEdis eleele andandEtot)Efor tot ) compound for compound2. All2.diagrams use the All diagrams same use the energy cylinder same energy scale of cylinder 240,ofand scale 240,the andenergy threshold the energy is 6.00iskJ·× threshold 6.00mol −1 .Electrostatic −1. (a) kJ·mol energy. (a) Electrostatic (b) energy. Dispersion (b) energy. Dispersion (c) (c) energy. Total energy. Total energy.(d)(d) BSMs BSMsAAand andBBpinpointing pinpointingthethemain main interactions interactions and and their energy values in kJ·mol kJ·× mol−1−1 .. The computed computed lattice latticeenergy energy(E (Elatlat))value valueofofeach eachunique uniquemolecule moleculehashasbeen beencalculated according calculated to according Equation to (1), (1), Equation in which Ni is N in which the number i is the number of molecule pairs in pairs of molecule the cluster in thewith that particular cluster with that interaction particular energy and E is interaction energy i the interaction energy value. and Ei is the interaction energy value. 11 X 𝑁 𝐸 n E𝐸lat = 2 (Ni ·Ei ) (1) (1) 2 i=1 The average Elat value of each HPip and Isn coformers has been calculated, and the crystal Elat is The average Elat value of each HPip and Isn coformers has been calculated, and the crystal computed considering the 2:1 (HPip:Isn) molar ratio. The crystal structure Elat value of 2 is −362.8 kJ·× Elat is computed considering the 2:1 (HPip:Isn) molar ratio. The crystal structure Elat value of 2 is mol−1, which is comparable to other reported energies of multicomponent cocrystals [44]. −362.8 kJ·mol−1 , which is comparable to other reported energies of multicomponent cocrystals [44]. The energy frameworks of 3a are also driven by the electrostatic component, in which weaker The energy frameworks of 3a are also driven by the electrostatic component, in which weaker destabilizing energies (1.0 and 2.2 kJ·× −1 mol−1) belong to the occluded pentanol molecules (Figure destabilizing energies (1.0 and 2.2 kJ·mol ) belong to the occluded pentanol molecules (Figure S10a), S10a), while the most remarkable dispersion energy is promoted by the parallel Pip ligands along the while the most remarkable dispersion energy is promoted by the parallel Pip ligands along the c axis c axis (Figure S10b). When compared to 2, the dispersion energy of 3a is more significant and plays a (Figure S10b). When compared to 2, the dispersion energy of 3a is more significant and plays a relevant relevant role in this system. This is induced by the restriction on the orientation of the Pip ligands role in this system. This is induced by the restriction on the orientation of the Pip ligands caused by caused by the coordination to the metal center. the coordination to the metal center. The total energy frameworks confirm that the main interactions are those from Isn as mentioned The total energy frameworks confirm that the main interactions are those from Isn as mentioned in the structural description (Figure S10c). The amide···amide pattern stacks the monomeric units in the structural description (Figure S10c). The amide···amide pattern stacks the monomeric units along the [110] with an energy value of −63.5 kJ·× mol−1−1 and these chains are assembled through the along the [110] with an energy value of −63.5 kJ·mol and these chains are assembled through the N-H/C-H···O interactions with two energy values of −23.3 and −21.6 kJ·× mol−1−1. The crystal structure N-H/C-H···O interactions with two energy values of −23.3 and −21.6 kJ·mol . The crystal structure Elat value is −414.6 kJ·× mol−1 and it has also been calculated according to Equation 1. Elat value is −414.6 kJ·mol−1 and it has also been calculated according to Equation (1). 3. Conclusions We successfully isolated three different isonicotinamide based compounds by modifying the reaction conditions. The crystal structure elucidation of 2, 3a, and 4 allowed ascertaining the formation of a cocrystal (2), a monomer (3a), and an unusual coordination polymer (4). Isn ligand can Molecules 2019, 24, 4169 13 of 18 3. Conclusions We successfully isolated three different isonicotinamide based compounds by modifying the reaction conditions. The crystal structure elucidation of 2, 3a, and 4 allowed ascertaining the formation of a cocrystal (2), a monomer (3a), and an unusual coordination polymer (4). Isn ligand can acts as either hydrogen bond donor or acceptor or both by strong N···H-O and N-H···O interactions. Likewise, it has a potential role as mono- or bidentate linker coordinating to the Cu(II) center via N- or N,O-atoms, and these tendencies could promote the formation of the mixtures. Compound 2 is constructed by type I and type III synthons instead of type II, which is the most common association in Isn-containing systems. This could be driven by the strong hydrogen bond donor solvent (MeOH) used in the crystallization process which probably dissociated the weaker type II homomeric synthon present in Isn and facilitated the formation of the stronger type III interaction. The union of both, Isn and HPip, fulfill the pKa rule and supports the formation of a cocrystal instead of a salt. In the two complexes 3a and 4, both Pip and Isn ligands participated in the growth of the final scaffolds, but Isn outstands as the keystone in the formation of the products. In the precursor structure (1), the Pip units act as bidentate bridged while in 3a and 4, they exhibited a chelate and a monodentate coordination mode, respectively. Likewise, the Isn unit also adopts two coordination modes (monodentate (3a) or bidentate bridged (4)). The additional reflux period, in combination with the basic pKb of the Isn ligand, could drive the MeOH groups deprotonation and their consequent coordination to the Cu(II) ions in 4. It is noteworthy that Isn ligand has been the driving unit of both monomeric and coordination polymer, designing different molecular and supramolecular networks and downgrading Pip to an auxiliary ligand. Hirshfeld surface analyses pinpointed the role of Isn as synthon. Furthermore, energy framework calculations distinguished Isn as the driving cohesive force, while HPip itself mainly participates in the London dispersion forces. Lattice energy calculation showed a notable value as a consequence of the large number of interactions promoted by the Isn ligand. The formation of the cocrystal has enabled us to easily recognize the role of Isn as synthon and facilitated the better understanding of the driving forces in those systems. 4. Experimental Section Cu(II) acetate monohydrate (Cu(OAc)2 ·H2 O), 1,3-benzodioxole-5-carboxylic acid (piperonylic acid, HPip), and isonicotinamide (Isn); methanol (MeOH) and pentanol (C5 H11 OH) for recrystallization were used as solvents and were purchased from Sigma-Aldrich (Darmstadt, Germany). Deuterated dimethylsulfoxide (dmso-d6 ) was used for the NMR experiments and was purchased from Eurisotop (Saint-Aubin, France). All of them were used without further purification. The [Cu(µ-OAc)(µ-Pip)(MeOH)]2 (1) was previously synthesized in our research group [26,27]. Melting point was measured on an MPM-H2 KLEINFELD (Gehrden, Germany) melting point meter apparatus. Elemental analysis (C, H, N) were carried out on a Thermo Scientific (Waltham, MA, USA) Flash 2000 CHNS Analyzer. The FTIR-ATR spectra were recorded on a Perkin Elmer (Waltham, MA, USA) spectrometer, equipped with a universal attenuated total reflectance (ATR) accessory with diamond window in the range 4000–550 cm−1 . 1 H-NMR and 13 C{1 H}-NMR spectra were recorded on an NMR-FT Bruker400 (Karlsruhe, Germany) MHz spectrometer in dmso-d6 solution at room temperature (r.t.). All chemical shifts (δ) are given in ppm relative to TMS as internal standard. The electronic spectra in solution of MeOH (≈1.0 × 10−3 M) were run on an Agilent HP 8453 UV-Vis spectrophotometer with a quartz cell having a path length of 1 cm in the range of 500–900 nm. Spectroscopic characterization details of all compounds are in the Supplementary Materials (Figures S1–S7). Synthesis of (HPip)2 (Isn) (2) and [Cu(Pip)2 (Isn)2 ] (3): A methanolic solution (25 mL) of 1 (98.9 mg, 0.155 mmol) was added dropwise to a methanolic solution (15 mL) of Isn (38.1 mg, 0.312 mmol) and was stirred for 2 h at r.t. A mixture of colorless and violet crystals was obtained by slow evaporation of the solution on air for 10 days. Molecules 2019, 24, 4169 14 of 18 Synthesis of (HPip)2 (Isn) (2): A methanolic solution (15 mL) of HPip (100 mg, 0.602 mmol) was added dropwise to a methanolic solution (10 mL) of Isn (36.7 mg, 0.300 mmol) and was stirred for 4h at r.t. After that, reaction was concentrated until half of the volume. Suitable colorless crystals were obtained by slow evaporation of the solution on air for three days. Single crystals were filtered and washed with cold diethyl ether. 2. Yield: 49.5 mg (57%). Mp 193–194 ◦ C. Elem. Anal. Calc. for C22 H18 N2 O9 (454.39 g/mol): C 58.15; H 3.99; N 6.17. Found: C 58.02; H 3.84; N 6.14. FTIR-ATR (cm−1 ): 3321(m) [ν(N-H)], 3140(m) [ν(O-H)], 3075(w), 3072(w) [νar (C-H)], 2907(w) [νal (C-H)], 2791(w), 2650-2283(w), 1680(s) [ν(C=O)], 1620(m), 1551(m) [ν(C=C/C=N)], 1500(m), 1482(w), 1431(w), 1409(s), 1361(m) [δ(C=C/C=N)], 1280(w), 1254(w), 1233(m), 1164(m) [ν(C-O-C)], 1108(m), 1032(m), 1023(m) [δip (C-H)], 906(m), 763(m) [δoop (C-H)], 707(w), 674(w), 643(s) [δ(O=CN)], 583(w). 1 H-NMR (360 MHz, DMSO-d6 , Me4 Si, 298 K): δ = 8.71 [2H, d, 3 J = 5.8 Hz, CH-CH-N]Isn , 8.24 [1H, br, OCNHH-C]Isn , 7.76 [2H, dd, 3 J = 4.5 Hz; 4 J = 1.5 Hz, CH-CH-N] , 7.73 [1H, br, OCNHH-C] , 7.54 [2H, dd, 3 J = 8.1 Hz; Isn Isn 4 J = 1.5 Hz, CH-CH-C-O] HPip , 7.35 [2H, d, J = 1.5 Hz, CH-C-O]HPip , 6.99 [2H, d, J = 7.9 Hz, 4 3 13 1 CH-CH-C-O]HPip , 6.11 [4H, s, O-CH 2 -O]HPip . C{ H}-NMR (360 MHz, DMSO-d6 , Me4 Si, 298 K): δ = 166.89 [O2 C-C]HPip , 166.62 [OCNH2 -C]Isn , 151.29 [CH-CH-C-O]HPip , 150.34 [CH-CH-N]Isn , 147.63 [CH-C-O]HPip , 141.46 [OCNH2 -C]Isn , 125.15 [CH-CH-C-O]HPip , 124.82 [O2 C-C]HPip , 121.65 [CH-CH-N]Isn , 108.99 [CH-C-O]HPip , 108.19 [CH-CH-C-O]HPip , 102.10 [O-CH2 -O]HPip . Synthesis of [Cu(Pip)2 (Isn)2 ] (3): A methanolic solution (25 mL) of 1 (100 mg, 0.156 mmol) was added dropwise to a methanolic solution (15 mL) of Isn (39.0 mg, 0.319 mmol) and was stirred for 4h under reflux conditions. Solution turned dark blue, and a blue powder precipitated. The solid was filtered, washed with 5 mL of cold MeOH, and dried under vacuum. The powder was recrystallized in pentanol, and the resulting solution remained exposed to air until violet crystals of [Cu(Pip)2 (Isn)2 ]·C5 H11 OH (3a) were grown by slow evaporation after four days. 3. Yield: 87.3 mg (88%). Elem. Anal. Calc. for C28 H22 CuN4 O10 (638.05 g/mol): C 52.71; H 3.48; N 8.78. Found: C 52.82; H 3.64; N 8.64. FTIR-ATR (cm−1 ): 3333(br) [ν(N-H)], 3165(br) [ν(N-H)], 3072(w) [νar (C-H)], 2964-2860(br) [νal (C-H)], 1694(m) [ν(C=O)], 1630(m), 1617(m), 1557(m) [νas (COO)], 1543(m) [ν(C=C/C=N)], 1498(m), 1435(m) [νs (COO)], 1384(s) [δ(C=C/C=N)], 1343(m), 1247(s), 1165(m) [ν(C-O-C)], 1108(m), 1067(m), 1035(s) [δip (C-H)], 938(m), 924(m), 805(m) [δoop (C-H)], 772(s) [δoop (C-H)], 722(m), 682(m), 651(m), 629(m) [δ(O=CN)], 590(m). UV-Vis (MeOH, 1.10·10−3 M) λmax (ε) = 713 (77) nm. Compound 3a presented the same FTIR-ATR spectrum as 3 with small differences in the 3400–2900 cm−1 region due to the presence of ν(O-H) signals attributable to pentanol molecules. Synthesis of [Cu(Pip)2 (Isn)2 ] (3) and {[Cu3 (Pip)2 (OAc)2 (µ-Isn)2 (Isn)2 (µ-OCH3 )2 (MeOH)2 ] ·2MeOH}n (4): A methanolic solution (25 mL) of 1 (100 mg, 0.156 mmol) was added dropwise to a methanolic solution (15 mL) of Isn (127 mg, 1.04 mmol) and was stirred vigorously under reflux conditions for a week. Solution was evaporated until half of the volume and kept at 4 ◦ C for a month until simultaneous violet (3, Yield: 51.4 mg (26%)) and green (4, Yield: 34.1 mg (52%)) crystals were formed. These crystals were mechanically separated. 4. Elem. Anal. Calc. for C48 H54 Cu3 N8 O20 (1253.62 g/mol): C 45.99; H 4.34; N 8.94. Found: C 45.67; H 4.29; N 9.18. FTIR-ATR (cm−1 ): 3435(w), 3333(br) [ν(N-H)], 3276(w), 3211 (br) [ν(N-H)], 3071(w) [νar (C-H)], 2992-2830(w) [νal (C-H)], 1696(m) [ν(C=O)], 1631(m), 1602(s) [ν(C=O)], 1554(m) [νas (COO)], 1504(m) [ν(C=C/C=N)], 1490(m), 1436(s), 1418(s) [δ(C=C/C=N)], 1387(s) [νs (COO)], 1258(s), 1243(m), 1221(m), 1170(m) [ν(C-O-C)], 1113(m), 1079(m), 1067(m), 1033(s) [δip (C-H)], 1015(m) [δip (C-H)], 935(m), 920(m), 889(m), 856(m), 805(m), 774(s) [δoop (C-H)], 765(m) [δoop (C-H)], 732(m), 683(s), 627(s) [δ(O=CN)], 582(s) [δ(O=CN)], 565(m). UV-Vis (MeOH, 9.90·10−4 M) λmax (ε) = 706 (404) nm. 5. Crystallographic Data A colorless (2), a violet (3a), and a green (4) prism-like specimens were used for the X-ray crystallographic analysis. The X-ray intensity data were measured on a D8 Venture system equipped with a multilayer monochromator and a Mo microfocus (λ = 0.71073 Å). For 2–4, the frames were Molecules 2019, 24, 4169 15 of 18 integrated with the Bruker SAINT software package using a narrow-frame algorithm. All hydrogen atoms were refined using a riding model (AFIX) with an isotropic temperature factor equal to 1.2, the equivalent temperature factor of the atom to which are linked and thus, the bond lengths of X–H were fixed. The structures were solved and refined using the Bruker SHELXTL Software package and refined using SHELX (version 2018/3) [45]. For 2–4, the final cell constants and volumes are based upon the refinement of the XYZ-centroids of reflections above 20 σ(I). Data were corrected for absorption effects using the Multi-Scan method (SADABS). Crystal data and relevant details of structure refinement for compounds 2–4 are reported in Table 7. CCDC 1944986 (2), 1944988 (3a), and 1944987 (4) contain the Supplementary Data of this paper. Molecular graphics were generated using Mercury 4.1.2 software [46,47] with POV-Ray package [48]. Color codes for all molecular graphics: orange (Cu), red (O), blue (N), dark grey (C), and white (H). Table 7. Crystal and structure refinement data for compounds 2–4. 2 3a 4 Empirical formula C22 H18 N2 O9 C33 H34 CuN4 O11 C50 H62 Cu3 N8 O22 Formula weigh 454.38 726.18 1317.69 T (K) 100(2) K 100(2) 100(2) Wavelength (Å) 0.71073 Å 0.71073 0.71073 System, space group Triclinic, P 1 Triclinic, P 1 Triclinic, P 1 Unit cell dimensions a (Å) 9.6976(3) 8.0226(8) 7.8402(3) b (Å) 12.6877(6) 11.4099(12) 13.7091(6) c (Å) 16.1988(7) 11.9187(13) 14.3107(6) α (◦ ) 82.329(2) 1.114(4) 109.2060(10) β (◦ ) 81.3340(10) 96.344(4) 97.8040(10) γ (◦ ) 89.9900(10) 107.632(3) 99.7130(10) V (Å3 ) 1952.31(14) 988.10(18) 1401.15(10) Z 4 1 1 Dcalc (g × cm3 ) 1.546 1.220 1.562 µ (mm−1 ) 0.122 0.609 1.215 F(000) 944 377 681 Crystal size (mm3 ) 0.242 × 0.082 × 0.081 0.164 × 0.093 × 0.072 0.251 × 0.071 × 0.046 −11 ≤ h ≤ 12 −11 ≤ h ≤ 11 −9 ≤ h ≤ 8 hkl ranges −16 ≤ k ≤ 16 −16 ≤ k ≤ 16 −15 ≤ k ≤ 15 −21 ≤ l ≤ 21 −17 ≤ l ≤ 17 −16 ≤ l ≤ 16 2θ range (◦ ) 2.198 to 28.299 1.959 to 30.583 2.603 to 24.403 Reflections collected/ 69395/9659 [R(int) = 0.0953] 51118/6046 [R(int) = 0.0428] 32892/4577 [R(int) = 0.0309] unique/[Rint] Completeness to θ = 25.242◦ 99.9 99.6 99.6 Absorption Correction Semi-empirical Semi-empirical Semi-empirical Max. and min. transmis. 0.7457 and 0.6910 0.7461 and 0.6872 0.7451 and 0.6975 Full-matrix least-squares on Full matrix least-squares on Full matrix least-squares on Refinement method |F|2 |F|2 |F|2 Data/restrains/parameters 9659/1/597 6046/0/250 4577/3/382 Goodness of fit on |F|2 1.039 1.112 1.095 R1 = 0.0888, R1 = 0.0541, R1 = 0.0444, Final R indices [I > 2σ(I)] wR2 = 0.2189 wR2 = 0.1690 wR2 = 0.1110 R1 = 0.1360, R1 = 0.0591, R1 = 0.0519, R indices (all data) wR2 = 0.2559 wR2 = 0.1746 wR2 = 0.1172 Extinction coefficient n/a n/a n/a Largest. Diff. peak and hole 1.329 and −0.722 2.077 and −0.717 1.472 and −0.700 (e Å−3 ) Molecules 2019, 24, 4169 16 of 18 Supplementary Materials: The following are available online at http://www.mdpi.com/1420-3049/24/22/4169/s1, Figure S1. FTIR-ATR spectra of a. compound (HPip)2 (Isn) (2); b. Isn and c. HPip.; Figure S2. 1 H-NMR spectra of a. compound (HPip)2 (Isn) (2); b. HPip and c. Isn.; Figure S3. 13 C{1 H}-NMR spectrum of a. compound (HPip)2 (Isn) (2); b. HPip and c. Isn., Figure S4. FTIR-ATR spectrum of compound [Cu(Pip)2 (Isn)2 ] (3).; Figure S5. FTIR-ATR spectrum of compound [Cu(Pip)2 (Isn)2 ]·(C5 H11 OH) (3a).; Figure S6. FTIR-ATR spectrum of compound {[Cu3 (Pip)2 (OAc)2 (µ-Isn)2 (Isn)2 (µ-OCH3 )2 (MeOH)2 ]·2MeOH}n (4).; Figure S7. Electronic spectra of compounds 3 and 4 between 500 nm and 900 nm in MeOH solution.; Figure S8. Hirshfeld surface representation and fingerprint plot of 2. In detail view of a. each molecule which forms the BSMs and b. each intra-BSM interaction with the surface area implied in it.; Figure S9. Hirshfeld surface representation and fingerprint plot of a. 3a and b. 4.; Figure S10. Energy frameworks diagram of a. Eele , b. Edis , c. Etot for compound 3a. All diagrams use the same energy cylinder scale of 240 and the energy threshold was fixed at 3.0 kJ·mol−1 for Eele and 30.0 kJ·mol−1 for Edis and Etot . Color codes of energy frameworks are red (Eele ); green (Edis ); blue (Etot ) and yellow (destabilizing energies). Complete information about the crystal structure and molecular geometry is available in .cif format as Supporting Information. Author Contributions: For research articles with several authors, a short paragraph specifying their individual contributions must be provided. The following statements should be used “conceptualization, J.P.; methodology, F.S.-F and D.E..; software, F.S.-F; validation, J.P. and T.C.; formal analysis, F.S.-F and M.F.-B; investigation, F.S.-F and D.E.; resources, J.P. and T.C.; data curation, F.S.-F., M.F.-B. and T.C.; writing—original draft preparation, F.S.-F. and D.E.; writing—review and editing, J.P. and T.C.; visualization, F.S.-F; supervision, J.P.; project administration, J.P.; funding acquisition, J.P. and T.C.”, please turn to the CRediT taxonomy for the term explanation. Authorship must be limited to those who have contributed substantially to the work reported. Funding: This work was financed by CB615921 project, the Spanish National Plan of Research MAT2015-65756R, and 2017SGR1687 project from the Generalitat de Catalunya. The authors also acknowledge “Fundació La Caixa” for CB616406 endowment. F.S.-F. acknowledges the PIF pre-doctoral fellowship from the Universitat Autònoma de Barcelona. Conflicts of Interest: The authors declare no conflict of interest. References 1. Swiegers, G.F.; Malefetse, T.J. New Self-Assembled Structural Motifs in Coordination Chemistry. Chem. Rev. 2000, 100, 3483–3538. [CrossRef] 2. Desiraju, G.R. Hydrogen bonds and other intermolecular interactions in organometallic crystals. J. Chem. Soc. Dalton Trans. 2000, 21, 3745–3751. [CrossRef] 3. Cambridge Structural Database (CSD) (Version 5.37). 2016. Available online: https://libguides.caltech.edu/ crystallography/CSD#Applications (accessed on 14 November 2019). 4. Ye, B.-H.; Tong, M.-L.; Chen, X.-M. Metal-organic molecular architectures with 2,20 -bipyridyl-like and carboxylate ligands. Coord. Chem. Rev. 2005, 249, 545–565. [CrossRef] 5. Etter, M.C. Encoding and decoding hydrogen-bond patterns of organic compounds. Acc. Chem. Res. 1990, 23, 120–126. [CrossRef] 6. Desiraju, G.R. Supramolecular Synthons in Crystal Engineering—A New Organic Synthesis. Angew. Chem., Int. Ed. 1995, 34, 2311–2327. [CrossRef] 7. Nangia, A.; Desiraju, G.R. Supramolecular Synthons and Pattern Recognition. In Design of Organic Solids; Topics in Current Chemistry, 198; Weber, E., Aoyama, Y., Caira, M.R., Desiraju, G.R., Glusker, J.P., Hamilton, A.D., Meléndez, R.E., Nangia, A., Eds.; Springer: Berlin/Heidelberg, Germany, 1998; pp. 57–95. 8. Wang, Y.-Y.; Shi, Q.; Shi, Q.-Z.; Gao, Y.-C.; Zhou, Z.-Y. Syntheses, characterization and crystal structure of copper(II) α,β-unsaturated carboxylate complexes with imidazole. Polyhedron 1999, 18, 2009–2015. [CrossRef] 9. Choudhury, A.R.; Desiraju, G.R.; Dikundwar, A.G.; Dubey, R.; Duggirala, N.; Ghogale, P.P.; Ghosh, S.; Goswami, P.K.; Goud, N.R.; Jetti, R.R.K.R.; et al. Polymorphs, Salts, and Cocrystals: What’s in a Name? Cryst. Growth Des. 2012, 12, 2147–2152. 10. Germán-Acacio, J.M.; Hernández-Ortega, S.; Aakeröy, C.B.; Valdés-Martínez, J. Using Lewis acidity differences in chelating ligands to control molecular structure and supramolecular assembly of Cu(II) complexes. Inorg. Chim. Acta 2009, 362, 4087–4090. [CrossRef] 11. Ðakovic, M.; Jagličić, Z.; Kozlevčar, B.; Popović, Z. Association of copper(II) isonicotinamide moieties via different anionic bridging ligands: Two paths of ferromagnetic interaction in the azide coordination compound. Polyhedron 2010, 29, 1910–1917. [CrossRef] 12. Ataç, A.; Yurdakul, Ş.; Ide, S. Synthesis and vibrational spectroscopic studies of isonicotinamide metal(II) halide complexes. J. Mol. Struct. 2006, 783, 79–87. [CrossRef] Molecules 2019, 24, 4169 17 of 18 13. Mukherjee, A. Building upon Supramolecular Synthons: Some Aspects of Crystal Engineering. Cryst. Growth Des. 2015, 15, 3076–3085. [CrossRef] 14. Yenikaya, C.; Poyraz, M.; Sari, M.; Demirci, F.; İlkimen, H.; Büyükgüngör, O. Synthesis, characterization and biological evaluation of a novel Cu(II) complex with the mixed ligands 2,6-pyridinedicarboxylic acid and 2-aminopyridine. Polyhedron 2009, 28, 3526–3532. [CrossRef] 15. Cruz-Cabeza, A.J. Acid–base crystalline complexes and the pKa rule. CrystEngComm. 2012, 14, 6362–6365. [CrossRef] 16. Bhogala, B.R.; Basavoju, S.; Nangia, A. Tape and layer structures in cocrystals of some di- and tricarboxylic acids with 4,40 -bipyridines and isonicotinamide. From binary to ternary cocrystals. CrystEngComm. 2005, 7, 551–562. [CrossRef] 17. Liu, C.-S.; Wang, J.-J.; Yan, L.-F.; Chang, Z.; Bu, X.-H.; Señudo, E.C.; Ribas, J. Copper(II), Cobalt(II), and Nickel(II) Complexes with a Bulky Anthracene-Based Carboxylic Ligand: Syntheses, Crystal Structures, and Magnetic Properties. Inorg. Chem. 2007, 46, 6299–6310. [CrossRef] 18. Moulton, B.; Zaworotko, M.J. From Molecules to Crystal Engineering: Supramolecular Isomerism and Polymorphism in Network Solids. Chem. Rev. 2001, 101, 1629–1658. [CrossRef] 19. Arici, M.; Yeşilel, O.Z.; Acar, E.; Dege, N. Synthesis, characterization and properties of nicotinamide and isonicotinamide complexes with diverse dicarboxylic acids. Polyhedron 2017, 127, 293–301. [CrossRef] 20. Moncol, J.; Mudra, M.; Lönnecke, P.; Hewitt, M.; Valko, M.; Morris, H.; Svorec, J.; Melnik, M.; Mazur, M.; Koman, M. Crystal structures and spectroscopic behavior of monomeric, dimeric and polymeric copper(II) chloroacetate adducts with isonicotinamide, N-methylnicotinamide and N,N-diethylnicotinamide. Inorg. Chim. Acta 2007, 360, 3213–3225. [CrossRef] 21. Bhogala, B.R.; Thallapally, P.K.; Nangia, A. 1:2 and 1:1 Ag(I)-Isonicotinamide coordination compounds: Five-fold interpenetrated CdSO4 network and the first example of (pyridine)N-Ag-O(amide) bonds. Crystal Growth & Design, 4, 215-218. Cryst. Growth Des. 2004, 4, 215–218. 22. Lynch, M.B.; Lawrence, S.E.; Nolan, M. Predicting Nucleation of Isonicotinamide from the Solvent–Solute Interactions of Isonicotinamide in Common Organic Solvents. J. Phys. Chem. A 2018, 122, 3301–3312. [CrossRef] 23. Vishweshwar, P.; Nangia, A.; Lynch, V.M. Molecular complexes of homologous alkanedicarboxylic acids with isonicotinamide: X-ray crystal structures, hydrogen bond synthons, and melting point alternation. Cryst. Growth Des. 2003, 3, 783–790. [CrossRef] 24. Mohamed, S.; Tocher, D.A.; Vickers, M.; Karamertzanis, P.G.; Price, S.L. Salt or Cocrystal? A New Series of Crystal Structures Formed from Simple Pyridines and Carboxylic Acids. Cryst. Growth Des. 2009, 9, 2881–2889. [CrossRef] 25. Sánchez-Férez, F.; Bayés, L.; Font-Bardia, M.; Pons, J. Solvent dependent formation of Cu(II) complexes based on isonicotinamide ligand. Inorg. Chim. Acta 2019, 494, 112–122. [CrossRef] 26. Soldevila-Sanmartín, J.; Ayllón, J.A.; Calvet, T.; Font-Bardía, M.; Domingo, C.; Pons, J. Synthesis, crystal structure and magnetic properties of a Cu(II) paddle-wheel complex with mixed bridges. Inorg. Chem. Commun. 2016, 71, 90–93. [CrossRef] 27. Sánchez-Férez, F.; Guerrero, M.; Ayllón, J.A.; Calvet, T.; Font-Bardía, M.; Giner Planas, J.; Pons, J. Reactivity of homoleptic and heteroleptic core paddle wheel Cu(II) compounds. Inorg. Chim. Acta 2019, 487, 295–306. 28. Williams, D.H.; Fleming, I. Spectroscopic Methods in Organic Chemistry; McGrawHill: London, UK, 1995. 29. Dey, A.; Kirchner, M.T.; Vangala, V.R.; Desiraju, G.R.; Mondal, R.; Howard, J.A.K. Crystal Structure Prediction of Aminols: Advantages of a Supramolecular Synthon Approach with Experimental Structures. J. Am. Chem. Soc. 2005, 127, 10545–10559. [CrossRef] 30. Bavishi, D.D.; Borkhataria, C.H. Spring and parachute: How cocrystals enhance solubility. Prog. Cryst. Growth Charact. Mater. 2016, 62, 1–8. [CrossRef] 31. Shishkin, O.V.; Zubatyuk, R.I.; Shishkina, S.V.; Dyakonenko, V.V.; Medviediev, V.V. Role of supramolecular synthons in the formation of the supramolecular architecture of molecular crystals revisited from an energetic viewpoint. Phys. Chem. Chem. Phys. 2014, 16, 6773–6786. [CrossRef] 32. Seo, M.; Park, J.; Kim, S.Y. Self-assembly driven by an aromatic primary amide motif. Org. Biomol. Chem. 2012, 10, 5332–5342. [CrossRef] 33. Tothadi, S.; Desiraju, G.R. Unusual co-crystal of isonicotinamide: The structural landscape in crystal engineering. Philos. Trans. R. Soc. A 2012, 370, 2900–2915. [CrossRef] Molecules 2019, 24, 4169 18 of 18 34. Nakamoto, K. Infrared and Raman Spectra of Inorganic and Coordination Compounds. Applications in Coordination, Organometallic, and Bioinorganic Chemistry, 6th ed.; Wiley Interscience: New York, NY, USA, 2009. 35. Sutton, D. Electronic Spectra of Transition Metal Complexes, 1st ed.; McGraw-Hill: New York, NY, USA, 1968. 36. Morse, P.M.; Girolami, G.S. Are d0 ML6 Complexes Always Octahedral? The X-ray Structure of Trigonal-Prismatic [Li(tmed)]2 [ZrMe6 ]. J. Am. Chem. Soc. 1989, 111, 4114–4116. [CrossRef] 37. Friese, J.C.; Krol, A.; Puke, C.; Kirschbaum, K.; Giolando, D.M. Trigonal Prismatic vs Octahedral Coordination Geometry: Syntheses and Structural Characterization of Hexakis(arylthiolato) Zirconate Complexes. Inorg. Chem. 2000, 39, 1496–1500. [CrossRef] [PubMed] 38. Falvello, L.R. Jahn–Teller effects in solid-state co-ordination chemistry. J. Chem. Soc. Dalton Trans. 1997, 1, 4463–4475. [CrossRef] 39. Nimmermark, A.; Öhrström, L.; Reedijk, J. Metal-ligand bond lengths and strengths: Are they correlated? A detailed CSD analysis. Z. Kristallogr. 2013, 228, 311–317. [CrossRef] 40. Adison, A.W.; Rao, T.N. Synthesis, structure, and spectroscopic properties of copper(II) compounds containing nitrogen–sulphur donor ligands; the crystal and molecular structure of aqua[1,7-bis(N-methylbenzimidazol-20 -yl)-2,6-dithiaheptane]copper(II) perchlorate. J. Chem. Soc. Dalton. Trans. 1984, 1, 1349–1356. [CrossRef] 41. Gör, K.; Kürkçüoğlu, G.S.; Yeşilel, O.Z.; Büyükgüngör, O. One-dimensional bimetallic cyano complexes with nicotinamide and isonicotinamide ligands. J. Mol. Struct. 2014, 1060, 166–175. [CrossRef] 42. Gudavarthy, R.V.; Burla, N.; Kulp, E.A.; Limmer, S.J.; Sinn, E.; Switzer, J.A. Epitaxial electrodeposition of chiral CuO films from copper(II) complexes of malic acid on Cu(111) and Cu(110) single crystals. J. Mater. Chem. 2011, 21, 6209–6216. [CrossRef] 43. Wolff, S.K.; Grimwood, D.J.; McKinnon, J.J.; Jayatilaka, D. and Spackman, M.A. CrystalExplorer17.5; University of Western, Australia: Crawley, Australia, 2017. 44. Évora, A.O.L.; Bernades, C.E.S.; Piedade, M.F.M.; Conceição, A.C.L.; Minas da Piedade, M.E. Energetics of Glycine Cocrystal or Salt Formation with Two Regioisomers: Fumaric Acid and Maleic Acid. Cryst. Growth Des. 2019, 19, 5054–5064. [CrossRef] 45. Sheldrick, G.M. A short history of SHELX. Acta Crystallogr. Sect. A Found. Crystallogr. 2008, 64, 112–122. [CrossRef] 46. Macrae, C.F.; Edgington, P.R.; McCabe, P.; Pidcock, E.; Shields, G.; Taylor, R.; Towler, M.; Van de Streek, J.J. Mercury: Visualization and analysis of crystal structures. Appl. Crystallogr. 2006, 39, 453–457. [CrossRef] 47. Macrae, C.F.; Bruno, I.J.; Chisholm, J.A.; Edgington, P.R.; McCabe, P.; Pidcock, E.; Rodriguez-Monge, I.; Taylor, R.; Towler, M.; van de Streek, J.; et al. Mercury CSD 2.0—New features for the visualization and investigation of crystal structures. Appl. Crystallogr. 2008, 41, 466–470. [CrossRef] 48. Persistence of Vision Pty. Ltd. Persistence of Vision (TM) Raytracer; Persistence of Vision Pty. Ltd.: Williamstown, Australia, 2004; Available online: http://www.povray.org/ (accessed on 14 November 2019). © 2019 by the authors. Licensee MDPI, Basel, Switzerland. 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