Exploring the effect of substitution pattern on the symmetry of hydrogen-bonded supramolecular motifs in functionalized benzosiloxaboroles

Crystal structures of a series of 26 functionalized 3-hydroxybenzo[ c ][1,2,3]siloxaboroles were compared taking into account electronic and steric effects of substituents at the aromatic ring on the hydrogen-bond (HB) motifs involving B  OH groups. The supramolecular assemblies of those compounds show strong variation depending on the number, position and type of substituents. Thus, HB dimers, trimers, tetramers and chains are formed. Most 7-substituted derivatives are isomorphous and crystallize in the I 4 1 / a tetragonal space group of symmetry featuring cyclic propeller-like tetramers as a characteristic structural motif. DFT calculations revealed that all observed HB motifs are characterized by similar stabilization energies ranging from  25 –  35 kJ ‧ mol  1 per molecule, which rationalizes strong diversification of HB motifs in the studied structures.


Introduction
Arylboronic acids and their derivatives continue to attract an enormous interest in various areas of chemistry and medicine.2][3][4] They are characterized by improved thermodynamic stability and low toxicity.For instance, 5-fluorobenzoxaborole (tavaborole) is currently used for the treatment of onychomycosis, 5 while 5-(4'cyanophenoxy)benzoxaborole (crisaborole) possesses strong anti-inflammatory activity and is used as the nonsteroidal topical agent for treatment of mild-to-moderate eczema. 6,7nother interesting example would be epetraborole, which is in a phase II/III clinical study now (NCT05327803) as an antibacterial agent against Mycobacterium avium complex lung disease. 8The knowledge in structural aspects of these compounds may be important, e.g., it may enable a deeper understanding of mechanistic aspects of their interactions with molecular targets.Thus, the crystal structures of various benzoxaboroles and related oxaboracyclic systems were determined followed by further studies concentrated on mechanistic aspects of their action.The Cambridge Structural Database (version 2022.3.0)search gives 50 hits of benzoxaboroles including structures functionalized with halogen atoms, [9][10][11] alkoxy, [12][13][14][15][16] aryloxy 17 or formyl [18][19][20] groups at various positions of aromatic rings.Derivatives bearing alkyl, 13,21,22 aryl, [23][24][25][26][27] heteroaryl 28 or heterocyclic (morpholine, thiomorpholine, diazine etc.), 19,[29][30][31][32][33] groups at the C3 position were also structurally characterized.It is also worth noting that benzoxaboroles were used as co-crystal components with 4,4'bipyridine and related HB acceptors. 17,34r group has been focused on the synthesis and physicochemical characterization of heteroelement analogues of benzoxaboroles, paying a special attention to benzosiloxaboroles -a new class of benzo-fused heterocycles characterized by improved Lewis acidity, high stability and promising antimicrobial activity. 35,36They can be considered as silicon bioisosteres of benzoxaboroles, where methylene group is replaced by the bulkier SiMe 2 group (Scheme 1).Benzosiloxaboroles were identified as potent antifungal and antibacterial agents, especially against Gram-positive strains including S. aureus, S. epidermitis and E. faecalis. 37We have also found that they can be used as inhibitors of KPC/AmpC lactamases, which are enzymes responsible for antibiotic resistance developed in clinical bacteria strains.Benzosiloxaboroles also show high affinity towards biologically relevant diols such as dopamine, AMP and selected sugars, indicating their possible application in chemosensing devices. 35,38Synthetic routes are generally different between benzoxa-and benzosiloxaboroles opening new possibilities for functionalization, especially at C6 and C7 positions, e.g., in the vicinity of the silicon atom. 391][42] We have already published several crystal structures of these compounds but we did not perform their detailed analysis.Herewith, we present a comprehensive study focused on the evaluation of substituent effect on crystal packing of these compounds.The X-ray diffraction analysis was supplemented by relevant computational studies.Poland.Electronic Supplementary Information (ESI) available: selected single-crystal X-ray diffraction data, NMR spectra of new compounds.Corresponding authors: Krzysztof Durka: krzysztof.durka@pw.edu.plSergiusz Luliński: sergiusz.lulinski@pw.edu.pl 2 2 (8) HB dimers due to mutual interactions of boronic groups resembling the motif characteristic for arylboronic acids (ArB(OH) 2 ).4449 However, in contrast to arylboronic acids which can act as double donors and double acceptors of HB, oxaboroles contain only one hydroxyl group, which suppresses the further propagation of HB interactions within crystal structure.The dimeric motif was encountered in 20 out  2 2 (8) of 42 crystal structures of benzoxaboroles (erroneous structures and salts were excluded from the analysis).In the remaining cases, the BOH group is arranged in the HB interaction with R1 or R2 functional group (Scheme 2) or second crystal component, i.e., solvent molecule or co-crystal partner.In turn, the presence of HB acceptor next to the boronic group favours an intramolecular HB. 19,34 Taking into consideration only simple halogen, alkyl or alkoxy benzoxaborole derivatives, a dimeric motif featuring syn conformation of both BOH groups is strongly preferred as it appears in 15 out of 17 crystal structures.In the remaining two structures, (CSD refcodes: MIHLIB21 and QEXYUQ17) BOH groups adopt anti conformation forming an infinite molecular chain via repeatable HB interaction motif with an endocyclic oxygen atom.In the context of this study, the second structure deserves a special attention as the oxaborole C3 carbon atom is substituted with two methyl groups which increase steric hindrance in the vicinity of the endocyclic oxygen atom weakening the tendency towards dimerization.Thus, the occurrence of other structural motifs can be expected in similar systems including benzosiloxaboroles.
Dimers (20 structures) HB with R 1 or R 2 substituent or solvent (18 structures) Scheme 2. Main crystal motifs encountered in the crystal structures of benzoxaboroles according to CSD search.

Scope of investigated structures.
In the current studies we have investigated 27 crystal structures of benzosiloxaboroles.We have selected relatively simple compounds in order to understand the basic relation between molecular structure and the specificity of intermolecular contacts present in respective crystal structures.Consequently, we measured 23 new crystal structures of benzosiloxaboroles substituted with halogen atom (F, Cl, Br, I), CF 3 , CHO, CN, B(OH) 2 , and CO 2 Me groups at various positions of the aromatic ring (Table 1).They were abbreviated according to the position, quantity and type of substituent attached to aromatic ring.For instance, 6,7-difluoro-1,1-dimethyl-3hydroxybenzo[c] [1,2,3]siloxaborole was abbreviated as 67-dF.Notably, compound 56-dF was found to crystallize in two polymorphic forms abbreviated as 56-dF-I and 56-dF-II.We have also included in this study 4 already published structures, i.e., 4567-tF, 35 6-OMe-7-Cl, 42 6-OTBDMS-7-Cl 39 and 4-CHO-67-dF. 37Although there are also several other known crystal structures of benzosiloxaboroles, they are characterized by more complex molecular and crystal structures based on multiple hydrogen bond interaction with functional groups attached to the aromatic ring.Thus, they were excluded from the current analysis.Finally, we would like to point out that despite numerous attempts we have failed to grow single crystals of the unsubstituted benzosiloxaborole as, in contrast to functionalized derivatives, this compound is in a liquid state at ambient temperature.

Synthesis.
The synthesis of most studied compounds was reported in our previous publications (proper references are given in Table 1).
For the purposes of this study, we have obtained 5 new benzosiloxaboroles including 4-CF3, 5-F, 7-CF3, 7-TMS and 7-I.Compound 5-F was prepared from 2-bromo-4-fluoro-1iodobenzene using a protocol involving I/Mg exchange, 42 silylation with Me 2 Si(H)Cl and conversion of an intermediate arylsilane to a respective final product using a sequence of Br/Li exchange, boronation and hydrolysis (Scheme 3a).Both regioisomeric benzosiloxaboroles 4-CF3 and 7-CF3 were obtained from 2-bromobenzotrifluoride using a protocol similar to that elaborated for 5-F except that deprotonative lithiation with LTMP was performed prior to silylation (Scheme 3b). 50The key step in the synthesis of 7-CF3 was the basicity-gradientdriven thermally induced isomerization ("halogen dance" mechanism) of 2-bromo-3-(trifluoromethyl)phenyllithium to thermodynamically more stable 2-bromo-6-(trifluoromethyl)phenyllithium which gave rise to the desired arylsilane precursor pre-7-CF3.Compound 7-TMS was obtained from 1,3-dibromobenzene using a three-step sequence (Scheme 3c).First, 1,3-dibromo-2-(dimethylsilyl)benzene 37    benzosiloxaboroles follow those observed for arylboronic acids.Regarding the oxaborole ring geometry, the presence of longer Si-O (benzosiloxaboroles) vs. C-O (benzoxaboroles) bonds is reflected by smaller BOSi (93-96) vs. BOC (109-112) bond angles.Conversely, endocyclic CBO bond angles are larger in benzosiloxaboroles (112-114) than benzoxaboroles (106-110).These differences may also result in part from the presence of two methyl groups at the silicon atom compared to simple methylene fragment in most of benzoxaboroles.This socalled gem-dimethyl effect 51,52 was also observed for benzoxaborole substituted with two methyl groups at the oxaborole C3 carbon atom. 53In accordance with our previous studies, the elongation of an endocyclic BO bond in benzosiloxaboroles may be ascribed to some extent to a competitive SiO bond hyperconjugation 35 which reduces the basicity of the endocyclic oxygen atom despite the higher polarity of SiO vs. CO bond. 54Taking into consideration the lower basicity of the endocyclic oxygen atom and steric effect of the SiMe 2 group, it could be expected that, at the expense of centrosymmetric dimers, other HB motifs would be relatively favored for benzosiloxaboroles.
Similar to benzoxaboroles, the BOH group in benzosiloxaboroles typically adopts the syn conformation.The anti-conformation was naturally imposed by an intramolecular OH…O HB interaction with an adjacent carbonyl group in 4-CO2Me-7-F and 4-CHO-67-dF.Such a conformation was also observed for structures 6-F and 67-dF where a HB chain was the primary supramolecular motif.

Crystal structure analysis.
The majority of the studied compounds crystallize in the centrosymmetric triclinic (P-1) and monoclinic (in most cases P2 1 /c) crystal systems.In contrast, five out of eight 7monosubstituted derivatives form isomorphous networks with I4 1 /a crystal symmetry.Most of the studied systems crystallize in non-solvated forms and feature a compact molecular packing.Exceptionally, structure 7-BOH2 contains acetone molecules, while 6-F incorporates hexane molecules in its channel-type network.In most cases, the asymmetric unit (ASU) consists of one or two benzosiloxaborole molecules, although 56-dF-I and 67-dCl crystallize with 3 molecules in ASU.In the case of 56-dF-I, the primary HB motif is a trimer, while the structure 67-dCl comprises two types of HB motifs, i.e., a dimer and a molecular chain.In contrast, the second polymorphic form 56-dF-II crystallizes with only one molecule in ASU and forms centrosymmetric dimer.In the most peculiar case,  Note that some structures consist of more than one molecule in ASU (Table 1).
they possess the same conformation and are arranged in dimeric HB motifs, they have different crystal environments resulting from different involvement in secondary CH…O, O…Cl and C(π)…B interactions.
The comparative analysis shows that benzosiloxaboroles offer a significantly larger variety of HB motifs with respect to benzoxaboroles.Undoubtedly, the most abundant motif is a  2 2 dimer involving two HBs formed by BOH groups (Figure 2).(8) However, it is observed in only 11 out of 26 considered structures (42%), i.e., less frequently compared to benzoxaboroles (48%).These differences become much more pronounced (50% vs. 88%) when only derivatives bearing simple substituents (halogen, CF 3 , SiMe 3 and alkoxy) are to be considered.The dimers can either involve two molecules related by the center of symmetry or two symmetrically independent molecules.The latter case allows for a wider diversification of secondary intermolecular contacts.For example, in 6-Cl one molecule is involved in two sets of O exo …B and C(Si)H…C(π) interactions forming a discrete secondary dimeric motif, while its HB partner aggregates through C(Si)H…C(π) interactions forming an independent onedimensional chain.Moreover, dimers comprising two symmetrically non-equivalent molecules usually deviate from a planar arrangement.This is especially visible for the dimer of 7-TMS, where the siloxaborole planes are twisted by 32(1) (Figure 2b).
Unlike benzoxaboroles, benzosiloxaboroles show a strong tendency to form four-molecule assemblies.This is especially visible for the series of isomorphous derivatives substituted with fluorine, chlorine, bromine, trifluoromethyl and formyl groups at the 7-position, i.e., ortho with respect to the SiMe 2 group.They crystallize in the I4 1 /a tetragonal space group of symmetry and feature cyclic propeller-like tetramers as a  4 4 (8) main structural motif.Tetramers adopt the chair conformation and are held by four sets of OH…O exo and C(Ar)H…O endo HB interactions (Figure 3a).Although the aromatic substituents   8)] c HB arranging exocyclic (exo) or endocyclic (endo) siloxaborole oxygen atoms, d HB with acetone molecule, e calculations were not performed due to the basis set incompatibility for iodine atom, f the intramolecular HB energy was estimated from the energy difference between two rotamers with CO 2 Me/CHO groups either coplanar or perpendicular to siloxaborole ring plane.Thus only one value is provided, g optimization led to very different geometry from that observed in the crystal structure.
are outside the interaction region, we have found that they significantly affect the geometry of the HB inner structure.Specifically, the O…O distances decrease with the increase of the size of the substituent making the entire tetramer more compact (Table 2).In order to validate the observed structural tendencies, we have obtained further two derivatives carrying bulkier substituents, i.e., -iodine (7-I) and trimethylsilyl group Considering the chain HB motif in the crystal structure of 3,3-dimethylbenzoxaborole, 17 it can be expected that benzosiloxaboroles should also arrange in linear assemblies.Indeed, the analysis of the crystal structure of 6-F revealed that the repeatable interactions of anti-oriented hydroxyl groups (d O…O = 2.718(3) Å) yielded an infinite zig-zag chain ( 2 2 (4), Figure 4a).The adjacent chains are connected by weak C(Si)H…F and C(Si)H…C(π) interaction forming 3-dimensional channel-type assembly filled with disordered hexane molecules (Figure S3, ESI).The introduction of another fluorine atom at the 7-position (67-dF) preserves the linearity of the main structural motif, but also reorganizes the molecular pattern through involvement of the endocyclic oxygen atom in the  2 2 HB chain.Consequently, it consists of molecules where (6) exocyclic and endocyclic oxygen atoms alternately act as acceptors of HB to hydroxyl group (Figure 4b).Interestingly, the 67-dF structure features also an independent dimeric  2 2 (8) motif.Finally, the strong effect of functional groups possessing active HB sites is evident.For instance, in 7-BOH2 the heterodimeric interactions between boronic group and oxaborole ring lead to the formation of an infinite zig-zag chain (Figure  , Figure 5b). 1 1 (9) Interestingly, in the case of 7-CHO, the formyl group is not involved in an intermolecular HB interaction with the BOH group.As already discussed, this structure retains  4 4 (8) tetrameric motif characteristic for other 7-monosubstituted derivatives.A quite different situation occurs when the carbonyl group is inserted at the ortho position relative to BOH group

Theoretical calculations.
The comprehensive analysis of HB motifs in crystal structures of benzosiloxaboroles shows the O…O distances are in the range of 2.684-2.861Å, with a mean value of 2.750 Å and a standard deviation of 0.048 Å.This is comparable to benzoxaboroles where O…O distances range from 2.704-2.867Å with mean value of 2.755 Å, and phenylboronic acids where O…O distances range from ca. 2.67-2.90Å with average value of 2.75 Å.To further compare both classes of oxaboroles we have performed theoretical calculations using M06-2X functional with 6-311++G(d,p) basis set.The HB motifs were extracted from the corresponding crystal structures and then H atoms were  optimized keeping the positions of other atoms fixed.In the second approach, the geometries of HB motifs were fully optimized (Table 2).It comes out that both procedures yielded very comparable interaction energy values indicating that the geometries of HB motifs are only slightly affected by crystal environment.
We have also calculated the interaction energies for dimeric and tetrameric motifs for unsubstituted benzoxa-and benzosiloxaboroles (Table 3 tetramer is energetically more advantageous, although the (8)] energy differences are rather small.The energy of  2 2 (8) dimeric motifs in benzosiloxaboroles ranges from ca. 27  29 kJmol 1 (per one molecule) and is only slightly affected by the aromatic ring substitution.Comparing the interaction energies in dimeric motifs in oxaboroles and phenylboronic acids  2 2 (8) (22  25 kJmol 1 per one molecule), 45,55,56 formation of dimers is more advantageous for former systems due to higher basicity of an endocyclic oxygen atom, thus serving as a better HB acceptor.Energy values estimated for intramolecular and intermolecular HBs with CHO, B(OH) 2 and CO 2 Me functional groups are of a similar magnitude.Surprisingly, it appeared that the HB energy in tetramer is close to 31 kJmol 1 per one  4 4 (8) molecule, regardless of the substituent type.It is even higher when molecules are arranged in the tetrameric  3 3 (9)[ 2 2 (8)] assembly (34 kJmol 1 per one molecule).This implies that tetrameric motifs are energetically more favored compared to dimers.However, one should bear in mind that the occurrence of a particular crystal motif can be governed by the kinetic crystallization effects.For instance the fast crystallization of 56-dF from CHCl 3 resulted in the formation of phase 56-dF-II comprising classical dimeric motifs.A slower crystallization from the same solvent yielded the polymorph 56-dF-I featuring a trimeric HB motif.Furthermore, aromatic substituents may promote specific intermolecular interactions including CH…O, CH…C(π), C(π)…B, O…B, CH…F, CH...Cl, halogen bonds, etc., thus changing the crystallization preferences.
In order to get deeper insight into the relative crystal stabilities, we have performed periodic calculations for selected isomeric benzosiloxaboroles bearing one fluorine (5-F, 6-F, 7-F), chlorine (6-Cl and 7-Cl) or trifluoromethyl (4-CF3, 6-CF3, 7-CF3) substituent.The obtained results are compared in Table 4. Considering the monofluorinated isomeric series, it is clear that the cohesive energies correspond to the interaction energies of HB motif.8) should be noted that 4-CF3 is also characterized by the most compact structure within the CF3 series.This is reflected in a small lattice volume of 1120.6(6)Å 3 (per one molecule) compared to the other two systems [V(6-CF3) = 1152.9(1)Å 3 ; V(6-CF3) = 1145.2(2)Å 3 ).Such results indicate that the weak intermolecular interactions provide a similar contribution to the total stabilization energy, although some substituents and positions may significantly strengthen the lattice interactions.

Conclusions
The comparative study of 27 crystal structures of benzosiloxaboroles revealed that these compounds show higher structural diversity than benzoxaboroles.Besides  2 2 (8) dimeric motifs, they also form trimers and tetramers as well as infinite molecular chains.This can be rationalized by similar stabilization energies of various types of aggregates.The appearance of a particular motif is affected by the substitution of the aromatic ring, although the lattice stabilization energies are comparable within the studied series and show correlation with energies of respective HB motifs.In this context, the crystallization kinetics can be of equal importance.Although the dimers are generally energetically less advantageous than tetramers, their appearance in crystal structures can be strongly promoted by the crystallization process.The monomer-dimer equilibrium can be affected by a substituent at the aromatic ring through its interaction with solvent molecules.Besides, benzosiloxaboroles, which are slightly less stabilized in their dimeric forms than benzoxaboroles, dissociate more easily promoting the occurrence of other, energetically more favourable HB motifs.Please do not adjust margins

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It should be stressed that the interactions with halogen substituents are generally weak and thus only marginally affect the primary HB motifs.Nevertheless, the analysis of crystal structures clearly showed that even small variations in the position and number of these substituents completely change the HB pattern.This was especially visible for fluorinated series of benzosiloxaboroles.The main crystal motifs range from  2 2 dimer (4567-tF, 67-dF, 56-dF-II), trimer (56-dF-I), ( 4 4 (8) F) and (5-F) tetramers to (6-F) and 2 (6) (67-dF) chains.Although it is difficult to rationalize the relationship between the molecular and supramolecular structures for each of the discussed example, we have found that 7-monosubstituted derivatives tend to form cyclic  4 4 (8) tetrameric structures and the size of the substituent affects the geometry of a central HB motif.

Experimental Section General comments.
Solvents used for reactions were dried by heating to reflux with sodium/benzophenone and distilled under argon.Selected aromatic starting materials and other reagents including alkyllithiums, 2,2,6,6-tetramethylpiperidine, trimethyl borate, chlorodimethylsilane, and chlorotrimethylsilane were used as received without further purification.In the 13 C{ 1 H} NMR spectrum of 7-I the resonance of boron-bound carbon atoms was not observed as a result of their broadening by a quadrupolar boron nucleus. 1 H, and 13 C NMR chemical shifts are given relative to TMS using residual solvent resonances. 11B and 19 F NMR chemical shifts are given relative to BF 3 •Et 2 O and CFCl 3 , respectively.

Single crystal X-ray diffraction.
Single crystals were grown by a solvent-evaporation method under air from the CHCl 3 or acetone solutions.Single crystal of 6-F was obtained using the diffusion method with CHCl 3 /hexane solvent set.Single crystals of polymorphs 56-dF-I and 56-dF-II were obtained by slow/fast evaporation of a CHCl 3 solution, respectively.However, the data quality 56-dF-I was low.In all cases, a selected crystal was maintained at low temperature (100 K) with the use of Oxford Cryosystems nitrogen gas-flow device.Exceptionally, structure 6-F was measured at 130 K.The crystal structures were established in a conventional way via Xray data refinement employing the Independent Atom Model (IAM).Data reduction and analysis were carried out with the CrysAlisPro suites of programs. 57All structures were solved by direct methods using SHELXS-97 58 and refined using SHELXL-2016. 59All non-H atoms were refined anisotropically.All CH H atoms were placed in calculated positions with CH distances of 0.95 Å and U iso (H) = 1.2U eq (C).The position H atoms of hydroxy groups were located from a difference electron density maps.The OH distances were fixed to 0.84 Å with standard deviation of 0.01 Å and the directionality of OH was refined freely.The U iso parameter was set to 1.5U eq with respect to oxygen atoms.The crystal structure 6-F contains voids with disordered hexane molecules.The solvent contribution was subtracted from the data using SQUEEZE from the PLATON crystallographic package.In the case of 6-CHO-7F, the difference map revealed slight disorder of the formyl group.However, the refinement showed that the contribution of a second component is very small (2.5%).Similarly, in the case of 7-Cl, H2 atom from O-H group was found to be disordered over two positions.The refinement showed that the occupancy factor for the alternate hydrogen position is only 20%.Thus, for both structures the disorder was not included in the final refinement procedure.All-important crystallographic data including measurement, reduction, structure solution and refinement details are placed in Tables S1-S5 in Supporting Information or in the associated CIF files or can be retrieved from the Cambridge Crystallographic Data

Theoretical calculations.
Theoretical calculations were performed at M06-2X 60 /6-311++G(d,p) 61 level of theory using Gaussian16 program. 62The HB motifs were extracted from the crystal structures.The positions of non-H atoms were fixed, while H atoms were fully optimised.In the second approach, the geometry of HB motif was fully optimized.Following geometry optimization, the interaction energies were calculated using the supermolecular method including Basis Set Superposition Error (BSSE).The energy of an intramolecular HB was estimated from the difference between the electronic energies of two rotamers: one with functional group coplanar with the oxaborole and aromatic rings, and the second with functional group rotated by 90.The energy of a HB chain was calculated taking two neighboured molecules.][66][67] Grimme dispersion correction was applied.6870 Ghost atoms were selected up to 5 Å distance from the studied molecule in a crystal lattice, and were used for the basis set superposition error estimation. 71

2 2 ( 8 ) 6 -Figure 1 .
Figure 1.Histograms showing the distributions of bond distances (Å) and bond angles () within siloxaborole ring.The analysis was performed for 27 crystal structures of benzosiloxaboroles (23 new and 4 contained in the CSD).Note that some structures consist of more than one molecule in ASU (Table1).

( 7 -
TMS).However, both structures feature dimeric motifs indicating that the formation of dimeric or tetrameric motifs can be controlled by the size of a substituent.The analysis of crystal structures of 5-F and 67-dCl revealed a different tetrameric assembly (graph set notation ).It consists of two molecules forming central  3 3 (9)[ 2 2 (8)] dimeric structure to which two other molecules are attached by CrystEngComm Accepted Manuscript Open Access Article.Published on 20 October 2023.Downloaded on 11/1/2023 10:50:13 AM.This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.View Article Online DOI: 10.1039/D3CE00880K Please do not adjust margins Please do not adjust margins lateral HBs (Figure 3b).It is supported by the pairs of auxiliary C(Ar)H…O exo and C(Si)H…O endo interactions.A somewhat related ternary assembly motif (graph set notation ) was found for 56-dF-I where one pendant siloxaborole molecule is attached to a central dimer (Figure S3, ESI).
Both functional moieties adopt rare arrangements as the boronic group in syn-syn configuration serves as a double HB donor to endo-and exocyclic oxaborole oxygen atoms while the anti-oriented oxaborole BOH group acts as a HB donor to the acetone molecule.The HB distance with the endocyclic oxygen atom (d O…O = 2.748(1) Å) is much shorter with respect to the exocyclic one (d O…O = 2.814(1) Å).Furthermore, the HB interaction with acetone (d O…O = 2.696(1) Å) is one of the shortest in the studied series.In two other examples (6-CHO-7-F, 6-CHO-57-dF), the supramolecular arrangement is governed by relatively strong HBs (6-CHO-7-F: d O…O = 2.732(1) Å, 6-CHO-57-dF: d O…O = 2.719(1) Å) between boronic and formyl groups resembling the linear HB pattern (

Figure 6 .
Figure 6.A fragment of crystal structure of 4-CO2Me-7-F showing the formation of intramolecular HB and further molecular connection through C(Ar)H…O interactions marked with grey dashed lines.

Table 1 .
The scope of investigated benzosiloxaboroles.

Table 2 .
Summary of HB motifs and interaction energies in crystal structures of benzosiloxaboroles.Interaction energies were calculated at M06-2X/6-311++G(d,p) level of theory following the two schemes: E int const -the positions of non-H atoms were retained from the crystal structure and H atoms were optimized, E int opt -all parameters were fully optimized.

6-OMe-7-Cl
a The structure comprises two types of HB motifs -dimer () and chain ( ), b lateral HB with pendant benzosiloxaborole molecule from tetramer,

Table 3 .
Interaction energies (kJ•mol 1 , per one molecule) in respective HB dimers and two types tetramers of benzoxaborole and benzosiloxaborole.

Table 4 .
Cohesive energies (E coh ) given per one molecule (B3LYP/pobTZVP level of theory with Grimme and BSSE correction included).The main HB structural motif is additionally provided in brackets.