controlling the solid - state 
 behavior of molecules through the use 
 of weak interactions is a long - standing goal of supramolecular chemistry . 

two of the most popular approaches involve exploiting reversible metal 
 coordination and hydrogen bonding .
the strength of hydrogen bonding interactions relative to other 
 weak interactions means that it plays an important role in the solid - state 
 behavior of supramolecular materials .
multiple hydrogen bonding interactions , such as the pairwise oh 
 interaction described in this work , impart enhanced stability to supramolecular 
 structures , such as in the multiple hydrogen bonds between complementary 
 dna base pairs ( figure 1 , top right ) .
this 
 behavior can be investigated through the use of hirshfeld surface 
 analysis , which allows visualization 
 of the different types of interactions present within a crystal structure . 

those pertinent to this work include hh , ch , 
 nh , oh , halogen bonding , and -based 
 interactions .
hirshfeld surfaces are produced through the partitioning 
 of space within a crystal where the ratio of promolecule to procrystal 
 electron densities is equal to 0.5 , resulting in continuous , nonoverlapping 
 surfaces .
. however , 
 its versatility means it can also be employed for larger supramolecular 
 assemblies , and hirshfeld surface analysis 
 is particularly useful in studying how different functionalities can 
 affect crystal packing behavior . in this 
 latter work , it was found that for para - substituted 
 phenols , changing the functionality from tert - butyl 
 to benzyl to nitro results in the dominant interaction in the structures 
 changing from hh to ch and oh 
 interactions , respectively .
this information is not readily apparent 
 solely from the crystal structure and explains the significant change 
 in packing behavior observed for these compounds .
dipicolinic acid derivatives 
 synthesized in this work ( left , center ) , 
 triple interaction between dna bases g and c ( top right ) , and the 
 pairwise oh interaction observed in 1 , 2 , 3 , 4 , and 6 ( bottom right ) .
dipicolinic acid and 
 its derivatives can form a variety of supramolecular 
 structures with lanthanides , including triple helices and polymeric 
 networks , with the luminescence of the lanthanides 
 often enhanced via strong , tridentate coordination to the dipicolinic 
 acid site .
coordination polymers with 
 copper , cobalt , and zinc have been reported , as has a la(iii)-based metal 
organic framework , which illustrates the versatility of these dipicolinic 
 acids in the formation of supramolecular structures .
the major feature 
 in all of these examples is tridentate coordination via the carboxylic 
 acids situated at the 2- and 6-positions of the pyridyl ring , allowing 
 charge delocalization to stabilize the structures . in order to allow 
 other structure - directing interactions such as hydrogen bonding to 
 be investigated
, the charge delocalization can be blocked and steric 
 interactions enhanced by the introduction of ester groups , thus suppressing 
 this tridentate binding mode .
herein we report the synthesis 
 of four 4-bromo dipicolinic acid 
 esters , 14 , systematically varying 
 the ester substituent in order to assess the effect of functional 
 groups on the solid - state behavior of these systems .
two of these 
 esters , 2 and 4 , are extended through a 
 coupling reaction to give conjugated systems 5 and 6 , respectively , in which the flexibility of the ester group 
 plays an important role in determining the nature of interactions 
 observed within the crystal structure .
the solid - state structures 
 of compounds 16 were studied through 
 the use of hirshfeld surface analysis , which has allowed visualization 
 of the proportion and nature of the interactions present in the structures , 
 some of which are not readily apparent through examination of the 
 crystal structure alone .
the importance of the double oh 
 interaction ( figure 1 , bottom right ) as a structure - directing 
 motif is highlighted , and the impact on this interaction of varying 
 the ester substituents is discussed .
4-bromopyridine-2,6-dicarboxylic acid was synthesized according 
 to a literature procedure and 14 obtained via reaction with the corresponding 
 alcohols .
compounds 5 and 6 were synthesized 
 via suzuki coupling procedure using 2 and 4 , respectively .
single crystals of 14 suitable for x - ray diffraction studies 
 were obtained by recrystallization in diisopropyl ether , and crystals 
 of 5 and 6 were grown by recrystallization 
 of the compounds from ch2cl2 and meoh .
compound 1 crystallizes in the triclinic space group p1 with two molecules in the asymmetric unit . these 
 molecules stack in an eclipsed manner down the a axis 
 with no  stacking interactions evident .
there 
 is a pairwise oh interaction of 2.378(4 )  , 
 c = oh = 154 , between the carbonyl 
 oxygen from one molecule and an aromatic proton from an adjacent molecule 
 ( highlighted in cyan in figure 2a ) .
this feature 
 is also observed in compounds 2 and 3 and 
 appears to be the main structure - directing interaction within the 
 crystal structure . a short contact [ 2.30(3 )  ]
is also observed 
 wherein one of the methyl protons interacts with the pyridyl nitrogen 
 and is highlighted in green in figure 2a .
interestingly , 
 this is the only bromopyridyl compound where the pyridyl nitrogen 
 participates in intermolecular interactions , a feature discussed further 
 below .
( a ) packing diagram with short contacts highlighted : nh 
 ( green ) , pairwise oh ( blue ) , other oh 
 ( orange ) , and hh ( black ) .
( b ) fingerprint plot with 
 characteristic interactions circled : nh ( green ) , 
 oh ( blue ) , and brh ( yellow ) .
( c ) dnorm surfaces displaying the pairwise oh 
 interaction ( blue ) and ( d ) nh interaction ( green 
 circles ) for 1 .
when hirshfeld surfaces were proposed as an effective way 
 to discern 
 intermolecular interactions in the solid state , the first properties 
 to be mapped on this surface were de and di , the distances of an atom external or internal 
 to the generated hirshfeld surface .
combining these two values results 
 in a ( di , de ) pair , and binning these into intervals of 0.01  ( essentially 
 a pixel on the hirshfeld surface ) results in the generation of a fingerprint 
 plot , where the different colors on the fingerprint plot represent 
 the frequency of occurrence of the interaction , increasing from blue 
 to green to red . taking these ( di , de ) pairs and normalizing them with respect to 

the van der waals radii of their corresponding atoms results in the dnorm surface , with contacts shorter than the 
 sum of the van der waals radii of the two atoms resulting in a negative 
 value and being highlighted on the dnorm surface in red .
contacts close in length to the van der waals limit 
 are colored white , and blue represents longer contacts .
the hirshfeld surface analysis for 1 shows the lowest 
 proportion of hh interactions for all of the structures 
 studied , making up only 25.9% of the surface .
this is to be expected 
 since 1 has only methyl esters with proportionally fewer 
 hydrogen atoms than compounds 26 .
only one short hh contact is present due to a 
 hydrogen from a methyl group interacting with an adjacent aromatic 
 hydrogen [ 2.330(6 )  ,  = 112 , highlighted in black 
 in figure 2a ] .
oh and ho 
 interactions combined , represented as spikes circled by blue in figure 3b , comprise 26.0% of the surface .
one close contact 
 is the pairwise interaction also seen in compounds 2 , 3 , and 6 , whereby a carbonyl oxygen interacts 
 with an aromatic proton , highlighted in blue in figure 2c .
the other close contact results from an och3 oxygen oriented toward a hydrogen from a neighboring methyl group 
 [ 2.61(4 )  ,  = 119 , highlighted in orange in figure 2a ] .
brh interactions , circled 
 in yellow in figure 2b , comprise 10.4% of the 
 hirshfeld surface but are all moderate to long contacts ( 3.04.4 
  ) .
a short bro contact [ 2.98(7 )  ] is 
 also present for one of the molecules in the asymmetric unit , where 
 the br atom is directed toward the carbonyl oxygen that does not participate 
 in the oh double interaction .
nh 
 contacts , highlighted in green in figure 2a , 
 only make up 1.4% of the hirshfeld surface but are significant because 
 it is only in 1 and 6 that nh 
 contacts are observed at all . when larger ester groups are employed , 
 the nitrogen is sterically blocked and can not participate in intermolecular 
 interactions . in the case of 1 ,
a neighboring methyl 
 proton is directed toward the pyridyl nitrogen , resulting in a short 
 contact [ 2.60(3 )  ] ,  = 123 , circled in green on 
 the dnorm surface in figure 2d ) .
this interaction is the other major structure - directing 
 feature seen in this crystal structure and is the reason that 1 packs in a significantly different manner to 2 or 3 .
hirshfeld surface analysis of the other molecule 
 in the asymmetric unit reveals that aside from the aforementioned 
 bro contact , the interactions present for this molecule 
 only vary in their proportion ( < 0.2% ) and not in their nature .
compound 2 crystallizes in the monoclinic space group p21/n with one molecule in the asymmetric unit . the molecules pack in 
 a herringbone arrangement along the a axis , and stack 
 in an eclipsed manner down the b axis ( figure 3a ) . a zigzag chain of br atoms is visible when viewed 
 down the a axis ( figure 3b ) 
 and involves a short brbr contact of 3.639(7 )  
 ( brbrbr = 73.2 , 
 highlighted in figure 3a in purple ) . the pairwise 
 oh interactions are highlighted in blue in figure 3a [ 2.350(5 )  , (oh ) 
 = 165.9 ] and constitute the same motif as that observed in 1 , 3 , and 6 .
( a ) packing diagram down 
 the b axis showing short 
 oh ( blue ) and brbr ( purple ) contacts , 
 ( b ) packing down the a axis , ( c ) fingerprint plot 
 with brbr interactions highlighted ( purple ) , and 
 ( d ) dnorm surface for 2 .
hirshfeld surface analysis of 2 shows that hh 
 contacts make up 37.7% of the surface , with one short contact present 
 between an aromatic proton and an ester proton from a nearby molecule 
 ( 2.797(4 )  ,  = 109.4 , highlighted in black in 
 figure 3a ) .
the proportion of hh 
 interactions has increased from 1 since the longer alkyl 
 chain affords a higher proportion of hydrogen atoms in the structure . 

oh and ho interactions comprise 
 21.8% of the surface , with one close contact arising from the interaction 
 of an oxygen center from an och2ch3 moiety with 
 a neighboring methylene proton .
this interaction occurs down the b axis and is perpendicular to the pairwise oh 
 interaction described above , unlike the related interaction observed 
 for 1 in which the ester och3 oxygen interacts 
 with a hydrogen on an adjacent methyl group , in the same plane as 
 the pairwise oh interaction .
the zigzag chain 
 of br atoms seen in the crystal structure of 2 is displayed 
 on the fingerprint plot as a bright streak 
 circled in purple in figure 3c , representing 
 only 2.9% of the surface .
this low percentage only relates to a proportion 
 of interactions ( given that there is only one br in the structure , 
 this number will generally be low ) and does not reflect the strength 
 and structure - directing effect that such an interaction has on the 
 solid - state behavior of the molecule .
previous studies on halogenhalogen 
 interactions 
 have shown that generally one of two different types of interaction 
 will occur .
a type - i interaction is when 
 1  2 ( where 1 is the angle c  br1br2 and 2 is the angle c 
br2br1 ) and a type - ii is characterized 
 by 1  90 and 2  
 180. in the case of 2 , a type - i interaction with 1  2  133 exists as a consequence of close packing 
 that serves to minimize repulsion between adjacent br atoms .
the two ethyl ester moieties of 2 do not allow the pyridyl nitrogen to participate in any intermolecular 
 interactions , a key difference from 1 , resulting in a 
 different packing motif that forces the br atoms to be oriented toward 
 each other and producing the alternating chain of br atoms .
although 
 the more flexible ethyl esters force a deviation from the formation 
 of planar sheets observed in 1 , the pairwise oh 
 interaction remains and is in fact shorter than that observed in 1 .
compound 3 crystallizes in the monoclinic 
 space group p21/n with one molecule present in the symmetric 
 unit .
disorder of one 
 of the propyl groups over two positions was modeled prior to hirshfeld 
 surface analysis . a herringbone arrangement down the b axis similar to compound 2
is observed , but no corresponding 
 zigzag arrangement of br atoms is seen ; instead , the br atoms are 
 involved in an end - on interaction with each other , similar to that 
 observed in 4 below .
again , the pairwise oh 
 interaction [ 2.311(3 )  ] and eclipsed stacking down the a axis are evident .
figure 4a shows 
 that when viewed across the bc plane there is a hexagonal 
 shaped circuit of close contacts ( outlined in orange ) in the plane 
 involving the pairwise oh interaction ( highlighted 
 in blue ) and a short hh contact ( highlighted in 
 black ) .
it is noteworthy that as the length of the alkyl substituent 
 has increased , this pairwise oh interaction distance 
 has shortened from 2.378 to 2.350 to 2.311  for 1 , 2 , and 3 , respectively .
this is consistent 
 with the larger alkyl substituents affording greater flexibility within 
 the structure , resulting in more efficient packing and a shorter pairwise 
 oh interaction distance .
( a ) packing diagram highlighting 
 a circuit of close contacts ( orange ) , 
 short oh contacts ( blue ) , and hh 
 ( black ) contacts , ( b ) fingerprint plot with brbr 
 interactions circled ( purple ) and ( c ) dnorm surface showing the pairwise oh interaction for 3 .
hirshfeld surface analysis of 3 shows unsurprisingly 
 that it contains the highest proportion of hh interactions 
 for compounds 14 ( 44.7% ) , a consequence 
 of the higher proportion of hydrogen atoms in the structure afforded 
 by the longer alkyl esters . of the atoms present in 3 ,
45.7% are hydrogens in contrast to 41.3% and 34.8% for 2 and 1 , respectively , so it is no surprise that hh 
 interactions dominate the hirshfeld surface .
short contacts arise 
 both from interactions between ester protons and from an aromatic 
 proton directed toward an ester proton in a manner analogous to that 
 observed in 2 , which is to be expected given their similar 
 packing arrangements . of the compounds 14 ,
compound 3 contains the highest proportion 
 of long ( 4.05.5  ) hh contacts due 
 to the disordered nature of one propyl chain resulting in more space 
 between adjacent br atoms than for 1 or 2 ( see figure 4a ) .
this results in the appearance 
 of asymmetric  wings  at the top of the fingerprint 
 plot ( figure 4b ) and is reflected in the lower 
 crystal density ( 1.547 g / cm for 3 compared 
 with 1.844 and 1.637 g / cm for 1 and 2 , respectively ) . oh and ho 
 interactions only comprise 17.2% of the surface and , again owing to 
 the similarity of the structures , their nature is very similar to 
 that observed in 2 , with one short contact due to the 
 pairwise oh interaction , figure 4c .
where 3 differs from 1 and 2 is that the other carbonyl oxygen ( i.e. , the one not participating 
 in the pairwise interaction ) is involved in a short contact with a 
 methylene proton from a neighboring ester group , whereas for 1 and 2 this carbonyl is not involved in any 
 short contacts .
brbr interactions are also present 
 in 3 as in 2 , but the distance between adjacent 
 br atoms is larger [ 3.792(6 ) in 3 vs 3.639(7 )  
 in 2 ] , resulting in a shift in the position of the brbr 
 streak in the fingerprint plot , figure 4b . 

it should be noted that as in 2 , the brbr 
 interaction is a type - i interaction , but in this case , 1  2
 156 , compared 
 to 133 for 2 . given the solid - state packing 
 observed in 13 , it was argued that 
 a bulkier ester substituent would result 
 in a completely different packing mode , which could allow us to investigate 
 other possible interactions between dipicolinic cores . with this in 
 mind , we synthesized the analogous benzyl ester 4 to 
 examine whether the dominant structure - directing feature would change 
 from the pairwise oh interaction observed in 13 . compound 4 crystallizes 
 in the triclinic space group p1 with one molecule 
 in the asymmetric unit .
the benzyl groups are tilted at 43 and 
 41 in relation to the pyridyl ring , and the molecules pack in 
 an alternating  up  down  arrangement down the a axis ( figure 5a ) .
there is a form 
 of pairwise oh interaction present , but this interaction 
 is markedly different to that observed in 13 and 6 . in 4 , this short contact 
 occurs between ch2 protons from the benzyl ester and a 
 carbonyl oxygen , highlighted in blue in figure 5a .
it does not involve an aromatic pyridyl proton , unlike the pairwise 
 interactions observed in 13 .
this 
 results in an increase in the oh interaction distance 
 [ 2.625(5 )  for 4 vs ca .
the change in this interaction can be attributed 
 to the bulkier nature of the ester substituent since a similar packing 
 arrangement and associated pairwise oh interaction 
 to those observed for 13 would result 
 in large void spaces throughout the molecule .
a short end - on brbr 
 contact is also observed in the structure , highlighted by the purple 
 interaction in figure 5a .
this contact is a 
 type - i interaction ( 1  2  143 ) similar to that observed in 3 , 
 but it is much shorter in this instance [ 3.489(7 )  in 4 vs 3.792(6 )  in 3 ] , as can be seen in 
 figure 5(b , circled ) .
( a ) packing diagram with 
 oh ( blue ) and brbr 
 ( purple ) contacts highlighted , ( b ) fingerprint plot with brbr 
 region circled ( purple ) , ( c ) shape index with areas of complementarity 
 identified ( paired circles ) , and ( d ) dnorm surface showing pairwise oh interactions for 4 .
shape index is a feature of hirshfeld 
 surface analysis that allows 
 for identification of complementarity between molecules in the crystal 
 packing structure .
features on the shape index surface that have an 
 identical pattern but opposite colors indicate areas of intermolecular 
 complementarity .
these areas are clearly visible in figure 5c and are circled in paired colors . from the shape 
 index surface
it can be seen that the br atom from one molecule of 4 sits between two benzyl moieties that are curved toward 
 it , circled in red in figure 5c .
the crosses 
 circled in purple correspond to the nitrogen of the pyridyl ring sitting 
 between the two methylene groups from the benzyl moieties , and the 
 matching black circles depict an area of complementarity where an 
 aromatic proton from the pyridyl ring is positioned over a benzyl 
 group .
this complementarity helps to understand the alternating up  down 
 packing arrangement along the a axis .
hirshfeld 
 surface analysis of 4 shows an increased 
 amount of ch and hc interactions 
 compared to structures 13 , accounting 
 for 27.3% of the surface , in accordance with the replacement of alkyl 
 esters with a benzyl group .
the increased proportion of ch 
 interactions does not manifest itself as short contacts or ch 
 interactions within the structure , instead appearing as medium or 
 longer range contacts ( 3.24.4  ) . as would be expected , 

a smaller proportion of oh contacts are observed , 
 making up only 12.7% of the surface .
the only short contact is due 
 to the pairwise interaction described above , which occurs for both of the carbonyl oxygens , figure 5d .
this is significantly different to that seen in 13 , where the pairwise interaction is only present 
 for one of the carbonyl oxygens . as a result ,
4 displays a chain of pairwise oh interactions 
 down the b axis that is not observed for 13 .
hh interactions comprise 
 33.8% of the surface , and a short contact exists between a methylene 
 proton and the neighboring hydrogen from a benzyl moiety . although 
 only 1% of the surface is assigned to brbr interactions , 
 a bright streak is still visible at the top right of the fingerprint 
 plot ( as for 2 and 3 ) , circled in purple 
 in figure 5b . like the brbr 
 interactions observed in 2 ,
this is a type - i interaction , 
 minimizing electrostatic repulsion between br atoms , with 1 = 2 = 142.6. the primary difference 
 from 2 is that this interaction occurs as indiscrete 
 brbr pairs and not within a continuous chain throughout 
 the structure .
in addition to systematic alteration of the ester 
 groups , these 
 dipicolinic acids were extended synthetically at the position para to the pyridyl nitrogen and the behavior of the subsequent 
 derivatives investigated .
extension of the compounds was achieved 
 through a suzuki coupling employing the 4-bromo dipicolinic acid ester 
 of choice and 1,4-benzene diboronic acid . in this way we utilized 2 and 4 to produce compounds 5 ( ethyl 
 esters ) and 6 ( benzyl esters ) , respectively .
clearly 
 this strategy removes all possibility of halogen bonding and it was 
 postulated that the addition of more aryl rings to the compound would 
 encourage  and ch interactions . 

the effect of these interactions in altering the structure - directing 
 pairwise oh interactions observed in 14 is of particular interest and has implications 
 for the design and control of hydrogen - bonded supramolecular structures .
compound 5 crystallizes in the triclinic space group p1 with half a molecule in the asymmetric unit .
the 
 molecules are staggered along the a axis , with the 
 nitrogen from one pyridyl group directly above the center of the pyridyl 
 ring below it ( and vice versa ) essentially in abab layers ( figure 6a ) .
this -based interaction plays a critical 
 role in the solid - state structure of 5 .
the central phenyl 
 ring is tilted at 44 with respect to the pyridyl rings and results 
 in a chain of ch interactions through the 
 ester and the central phenyl rings , highlighted in red in figure 6c .
this is the first instance of ch 
 interactions observed for the dipicolinic acid esters reported herein 
 and suggests a significant change in the structure - directing interactions 
 for 5 .
further evidence for this change is provided by 
 the complete absence of the pairwise oh 
 interaction that is observed in compounds 14 , with this previously dominant feature now replaced by ch 
 and -stacking interactions . in this way , by extending the dipicolinic 
 acid 2 to form 5 we have completely removed 
 the pairwise oh interaction and demonstrated control 
 over the solid - state structure of the resulting material .
the absence 
 of any pairwise oh interaction is unique to 5 in this study , and we assign this to a combination of the 
 structural demands of the phenyl spacer , both in terms of the geometric 
 restrictions it imposes on the pyridyl rings and the -based 
 interactions it undergoes , and the use of the relatively small ethyl 
 ester .
further evidence for the effect of the latter is seen in the 
 structure of 6 and described further below .
hh 
 interactions make up the majority of the hirshfeld 
 surface for 5 , which is consistent with the high proportion 
 of hydrogen atoms in the structure .
although oh 
 and ho interactions contribute 23.4% to the surface , 
 it is important to note that the oh pairwise interaction 
 observed in 14 is no longer present 
 in this structure . instead , a short contact arises where the hydrogen 
 from one methyl group interacts with a carbonyl oxygen , clearly visible 
 on the dnorm surface in figure 6d .
a hydrogen from the other methyl group is oriented 
 toward the central phenyl ring , resulting in characteristic ch 
 interactions being clearly visible in figure 6b and on the fingerprint plot as 
although the nc 
 interaction observed in the structure comprises only a small fraction 
 of the hirshfeld surface ( 1.4% ) , it is not observed in 14 , and as such clearly plays a central role 
 in the behavior of 5 in the solid - state . as noted previously 
 in the text , the percentage of the hirshfeld surface does not necessarily 
 reflect the strength and structure - directing properties of the interaction .
the related observations that increasing steric bulk in compounds 13 decreased the pairwise oh interaction 
 distance and that in benzyl ester - containing 4 , both carbonyl groups were accessible for the pairwise interaction 
 rather than just one prompted us to consider whether a bulkier ester 
 functionality than that of 5 could reinstate the pairwise 
 oh interaction .
therefore , compound 4 was extended via a suzuki coupling identical to that described earlier , 
 yielding the benzyl ester - substituted 6 .
( a ) packing diagram , 
 ( b ) packing diagram illustrating ch 
 contacts ( red ) , ( c ) fingerprint plot showing ch 
 interactions ( red circles ) , and ( d ) dnorm surface for 5 . compound 6
crystallizes in the triclinic space 
 group p1 with two half - molecules in the asymmetric 
 unit . 

the central phenyl rings are tilted at 26 and 36 with 
 respect to the pyridyl rings for the two half - molecules , which is 
 less than for those in 5 . because of this decreased tilt 
 angle and the benzyl ester moieties being bulkier than the ethyl groups 
 in 5 , the central phenyl group is inaccessible for ch 
 interactions .
the benzyl ester moieties are twisted with respect to 
 the pyridyl ring at angles of 90 and 119 for one of the molecules 
 in the asymmetric unit , and 90 and 137 for the other molecule . 
 the compound packs in a herringbone arrangement along both the a and b axes , and the nc 
 interactions that are observed in 5 are no longer present 
 in 6 due to the bulky nature of the benzyl esters .
notably , we have re - established the pairwise oh 
 interaction in 6 , and as for compounds 13 , this is based upon the interaction of a carbonyl 
 oxygen with an aromatic proton . in this instance , however , the contact 
 distance is longer than for 13 [ 2.505(4 ) 
  compared to ca .
seen for 13 , only one of the carbonyl 
 groups at each end of the molecule engages in the pairwise oh 
 interaction , and the oxygen interacts with an aromatic proton , unlike 
 in 4 .
in fact , despite the same ester functionality , 
 the pairwise oh interaction in 6 has 
 more in common with those observed in 13 than in 4 .
this suggests that the most favored 
 form of the pairwise oh interaction is between a 
 carbonyl oxygen and an aromatic proton , and the increased bulk and 
 flexibility of 6 compared with 4 allows 
 this structure - directing interaction to be achieved .
( a ) packing diagram showing 
 the return of the pairwise oh 
 interaction ( blue ) and other oh single interactions 
 ( orange and pink ) , ( b ) fingerprint plot displaying ch 
 ( red ) and nh ( green ) interactions , and ( c ) dnorm surface with unique pairwise interaction 
 ( see text ) highlighted ( blue and orange ) for 6 . similar to 5 ,
hh 
 interactions comprise 
 the majority of the hirshfeld surface for 6 , making up 
 4042% for each molecule in the asymmetric unit .
this is the 
 only structure where no short hh contact exists , 
 with 15 displaying at least one 
 such interaction .
oh - based interactions are responsible 
 for 1619% of the surface in 6 , with one short 
 contact arising from the pairwise oh interaction 
 described previously .
this interaction can clearly be seen on the dnorm surface ( circled in blue , figure 7c ) .
two other oh close contacts 
 exist on the structure , one involving a carbonyl oxygen and a hydrogen 
 from the central phenyl ring ( circled in orange ) , and one between 
 the other carbonyl oxygen and a benzyl hydrogen , highlighted in pink 
 in figure 7a .
the first of these oh 
 close contacts involving the central phenyl ring differentiates the 
 pairwise oh interaction in 6 from those 
 observed in 13 since one of the 
 carbonyl oxygens of the pairwise interaction interacts with two aromatic protons ( the second proton is circled in orange 
 in figure 7c ) rather than simply one .
furthermore , 
 as described above , these oh interactions are significantly 
 different from those observed in 4 , further pointing 
 to the structure - directing role of the central phenyl spacer in the 
 solid - state behavior of these molecules . the smaller proportion 
 of hh and oh 
 interactions results in a larger proportion of ch 
 interactions , which comprise approximately 18% of the surface of 6 .
one of the half molecules in the asymmetric unit contains 
 a ch short contact , whereby a hydrogen from 
 the central phenyl ring is directed toward a benzyl ester group .
this is notably different to the type of ch 
 interaction observed in 5 , where the central phenyl spacer 
 acts as the source of  electrons as opposed to the source of 
 a hydrogen in 6 .
the same half - molecule contains a close 
 contact between a pyridyl nitrogen and a hydrogen from an adjacent 
 benzyl ester moiety , which can be seen on the fingerprint plot as 
 the spike circled in green in figure 7b .
this 
 intermolecular contact arises due to the flexible nature of the ester , 
 as the benzyl group of one molecule is able to rotate around the ch2 bond and position itself between two benzyl ester functionalities 
 present in the next molecule .
h interaction 
 with the pyridyl nitrogen in 1 , this is the only other 
 compound in the series to display a nh interaction . 

this interaction does not comprise a large portion of the hirshfeld 
 surface , but it does illustrate how the flexibility of the ester moiety 
 is able to influence the efficiency of packing within 6 , further supported by the increase in density of 6 over 
 that of 5 ( 1.39 vs 1.35 g / cm respectively ) .
we have synthesized four 
 4-bromo dipicolinic acid derivatives 14 in order to assess the effect of different 
 ester functionalities on the behavior of these molecules in the solid - state , 
 with the key interactions summarized in table 1 . for compounds 13
the dominant 
 structure - directing motif is a pairwise oh interaction 
 between a pair of carbonyl oxygens and aromatic protons , with the 
 length of this pairwise interaction decreasing for longer alkyl ester 
 chain lengths .
the carbonyl oxygen not involved in the pairwise interaction 
 only participates in a short contact in 3 , whereas interactions 
 incorporating the ester oxygens are only seen in 1 , most 
 likely due to the lack of steric hindrance associated with the methyl 
 group .
introduction of a bulky benzyl ester group in 4 results in a shift in the pairwise oh interaction 
 from an aromatic proton to a methylene proton and a concurrent lengthening 
 in the interaction distance .
compound 4 is also the only 
 compound in this series to display a pairwise oh 
 interaction involving both carbonyl functionalities . 
 for compounds
24 the pyridyl nitrogen 
 can not participate in any intermolecular interactions due to the sterically 
 bulky ester groups , but this is not the case for the smaller methyl 
 ester 1 , which displays a completely different structure . 

brbr interactions also play a role in the structures , 
 with close contacts observed for 2 and 4 . both of these are type - i interactions , which minimize steric and 
 electrostatic repulsion .
however , while they result in a zigzag chain 
 of br atoms in 2 , 4 displays discrete pairs 
 of brbr interactions .
the dipicolinic acid 
 esters 2 and 4 were 
 also extended para to the nitrogen , to give 5 and 6 , respectively , in which both contain 
 a phenyl spacer . a complete loss of the pairwise oh 
 interaction was observed in 5 , with the dominant structure - directing 
 motif now comprising -based interactions . in 5 the pyridyl nitrogen and the ester oxygens do not participate in 
 intermolecular interactions , as also seen in 24 . instead of participating in a pairwise interaction , the 
 carbonyl oxygens in 5 instead
interact with ester protons 
 in a manner similar to that observed in 3 . the introduction 
 of a bulkier yet more flexible benzyl ester in compound 6 results in the return of the pairwise oh interaction 
 as observed in 13 , but this pairwise 
 interaction is unique , distinguished by a third interaction between 
 one carbonyl oxygen and a proton from the phenyl spacer .
hirshfeld 
 surface analysis was employed for 16 , allowing quantification of these various interactions within the 
 structures and identification of contacts that are not immediately 
 apparent from individual crystal structures , such as the ch 
 interactions observed in 5 and 6 .
we have 
 shown through systematic variation of dipicolinic acid derivatives , 
 both at the ester positions and para to the pyridyl 
 nitrogen , that we can achieve a degree of control over the behavior 
 of these systems in the solid state and influence the dominant structure - directing 
 features that are present .
chelidamic 
 acid hydrate ( 500 mg , 2.74 mmol ) was mixed with phosphorus pentabromide 
 ( 5.0 g , 11.6 mmol ) and heated to 90 c until a viscous melt was 
 produced .
this melt was maintained at temperature for a further 1.5 
 h at which point it was cooled and chcl3 ( 10 ml ) added . 

the resulting yellow precipitate was filtered and the appropriate 
 alcohol ( 50 ml , methanol , ethanol , isopropanol , or benzyl alcohol 
 for 1 , 2 , 3 , or 4 , respectively ) added dropwise and the resulting solution stirred 
 for 16 h. the solvent was removed under reduced pressure , water ( 50 
 ml ) and ice ( 50 g ) added , and the resulting precipitate filtered .
diffraction data for 16 was collected 
 using -scans on an agilent supernova ccd diffractometer equipped 
 with a cu - k microfocus sealed tube x - ray source . 

structures were solved by direct methods 
 using shelxs97 and refined against f using shelxl97 .
unless otherwise stated , all non - h atoms were refined with anisotropic 
 atomic displacement parameters , while the hydrogen atoms were placed 
 in geometrically calculated positions .
the disorder was modeled by running 
 the hirshfeld surface analysis for both possible orientations of the 
 propyl esters . on the basis that the proportion of interactions varied 
 by < 0.4% , one orientation was selected and modeled as fully occupied .
2 ) , a = 3.9543(4 ) , b = 13.6225(17 ) , c = 18.749(2 )  ,  = 
 98.438(10 ) ,  = 93.014(9 ) ,  = 97.680(9) , v = 987.4(2 )  , z = 4 , t = 120(2 ) k , dcalcd = 1.843 
 g cm ,  = 5.673 mm , n(unique ) = 3267 ( merged from 6326 ) , rint = 0.0301 , r1 = 0.0323 , wr2 ( all data ) = 0.0858 , gof = 1.03 , max = 0.54 e  . c11h12brno4 , m = 302.13 , monoclinic p21/n ( no .
14 ) , a = 15.3907(6 ) , b = 4.33847(15 ) , c = 19.5380(8 )  , 
  = 110.046(4) , v = 1225.56(8 )  , z = 4 , t = 120(2 ) k , dcalcd = 1.637 g cm ,  
 = 4.630 mm , n(unique ) = 2336 
 ( merged from 14024 ) , rint = 0.0248 , r1 = 0.0214 , wr2 ( all 
 data ) = 0.0568 , gof = 1.05 , max = 0.31 e 
  .
mp 9091 c ; ir 
 max ( cm ) : 3073 , 2964 , 2938 , 
 2879 , 1716 , 1560 , 1463 , 1415,1394 , 1379 , 1349 , 1323 , 1300 , 1263 , 1173 , 
 1147 , 978 , 942 , 925 , 900 , 793 , 780 , 760 , 732 , 690 . h nmr 
 ( 270 mhz ) :  8.41 ( s , 2h ) , 4.38 ( t , j = 6.2 
 hz , 4h ) , 1.85 ( q , j = 7.5 hz , 4h ) , 1.04 ( t , j = 6.2 hz , 6h ) .
c nmr ( 67.5 mhz ) : c 163.6 , 149.6 , 135.0 , 131.1 , 68.2 , 22.0 , 10.4 . hrms ( ei ) m / z calcd for c13h17o4nbr , 330.043 ; found 330.034 .
calcd for c13h17o4nbr : c , 47.3% ; h , 4.9% ; n , 4.2% ; found 
 c , 47.2% ; h , 4.9% ; n , 4.2% .
14 ) , a = 11.4027(4 ) , b = 
 4.51826(15 ) , c = 27.8897(11 )  , 
  = 99.456(4) , v = 1417.36(9 )  , z = 4 , t = 120(2 ) k , dcalcd = 1.547 g cm ,  
 = 4.055 mm , n(unique ) = 2453 
 ( merged from 8675 ) , rint = 0.0308 , r1 = 0.0307 , wr2 ( all 
 data ) = 0.0765 , gof = 1.05 , max= 0.45 e  .
mp 8788 
 c ; ir 
 max ( cm ) : 3074 2965 , 2937 , 2879 , 
 2166 , 1716 , 1563 , 1379 , 1349 , 1325 , 1264 , 1239 , 1175 , 1147 , 944 , 925 , 
 900 , 780 , 700 , 690 .
h nmr ( 270 mhz ) :  8.42 ( s , 
 2h ) , 7.517.46 ( m , 4h ) , 7.437.34 ( m , 6h ) , 5.46 ( s,4h ) .
c nmr ( 67.5 mhz ) : c 163.6 , 149.6 , 135.0 , 
 131.2 , 128.8 , 128.7 , 128.6 , 127.4 , 68.1 .
calcd for c21h17no4br : c. 59.2% ; h. 3.8% ; n. 3.3% ; found c. 59.2% ; h. 
 3.8% ; n. 3.2% .
2 ) , a = 6.6580(4 ) , b = 10.5799(11 ) , c = 13.4275(4 )  , 
  = 
 87.325(5 ) ,  = 81.672(4 ) ,  = 75.385(7) , v = 905.55(12 )  , z = 
 2 , t = 120(2 ) k , dcalcd = 1.563 g cm ,  = 3.332 mm , n(unique ) = 3071 ( merged from 8212 ) , rint = 0.0433 , r1 = 0.130 , wr2 ( all data ) = 0.393 , gof = 1.81 , max = 6.72 e  .
compound 2 ( 700 mg , 
 2.32 mmol ) , benzene-1,4-diboronic acid ( 175 mg , 
 1.06 mmol ) , and k2co3 ( 801 mg , 5.80 mmol ) were 
 suspended in toluene ( 100 ml ) and water ( 25 ml ) .
the solution was 
 vigorously stirred and under ar for 1 h at 60 c .
after this 
 time [ pd2(dba)3 ] ( 214 mg , 0.23 mmol ) and p(bu)3 ( 0.50 ml , 0.54 mmol ) were 
 added and the solution refluxed at 80 c for 15 min .
the solution 
 was cooled , filtered through a silica plug using ch2cl2 , and the solvent removed under reduced pressure to afford 5 ( 534 mg , 97% ) as a crystalline white powder .
mp 241243 c ; 
 irmax(cm ) : 2984 , 1716 , 1601 , 
 1558 , 1474 , 1402 , 1374 , 1344 , 1323 , 1266 , 1242 , 1149 , 1111 , 1074 , 
 1026 , 994 , 941 , 912 , 883 , 866 , 844 , 780 , 752 , 736 , 729 , 703 , 555 .
h nmr ( 270 mhz , dmso - d6 ) : 8.58 
 ( s , 4h ) , 7.95(s , 4h ) , 4.55 ( q , j = 7.3 hz , 8h ) , 1.51 
 ( t , j = 7.4 hz , 12h ) .
c nmr ( 67.5 mhz , 
 dmso - d6 ) : c 164.7 , 149.7 , 
 149.5 , 137.9 , 128.2 , 125.5 , 62.6 , 14.3 ; hrms ( ei ) m / z calcd for c28h28o8n2na : 407.052 ; found 407.050 .
calcd for c28h28o8n22.6chcl3 : c , 47.9% ; h , 4.0% ; n , 3.4% ; found c , 48.0% ; h , 4.0% ; n : 3.8% .
2 ) , a = 6.7914(5 ) , b = 10.0137(7 ) , c = 10.9532(10 )  , 
  = 113.673(7 ) ,  = 92.345(6 ) ,  = 107.500(6) , v = 639.4(1 )  , z = 1 , t = 120(2 ) k , dcalcd = 1.352 
 g cm ,  = 0.831 mm , n(unique ) = 2253 ( merged from 4245 ) , rint = 0.0158 , r1 = 0.0352 , wr2 ( all data ) = 0.0966 , gof = 1.06 , max = 0.22 e  .
compound 4 ( 100 mg , 
 0.235 mmol ) , benzene-1,4-diboronic acid ( 18 mg , 
 0.107 mmol ) , and k2co3 ( 81 mg , 0.59 mmol ) were 
 suspended in toluene ( 20 ml ) and water ( 5 ml ) .
after this time [ pd2(dba)3 ] ( 22 mg , 0.023 mmol ) and p(bu)3 ( 50 l , 0.056 mmol ) were added and the 
 solution refluxed at 80 c for 15 min .
the solution was cooled , 
 filtered through a silica plug using ch2cl2 , 
 and the solvent removed under reduced pressure to afford 6 ( 60 mg , 73% ) as a white powder .
mp 263265 c ; 
 ir max(cm ) : 3071 , 2965 , 2940 , 
 2884 , 2145 , 1718 , 1560 , 1375 , 1344 , 1328 , 1264 , 1240 , 1148 , 943 , 895 , 
 780 , 705 .
h nmr ( 270 mhz ) : 8.53 ( s , 4h ) , 7.88 ( s , 
 4h ) , 7.547.50 ( m , 4h ) , 7.437.34 ( m , 6h ) , 5.51 ( s , 
 4h ) .
c nmr ( 67.5 mhz ) : c 163.9 , 152.3 , 
 149.7 , 149.4 , 137.9 , 129.4 , 128.8 , 125.8 , 125.6 , 121.8 . hrms ( ei ) m / z calcd for c28h28o8n2na : 769.255 ; found 769.248 .
2 ) , a = 9.6784(6 ) , b = 10.0930(8 ) , c = 19.0710(19 )  , 
  = 88.546(7 ) ,  = 85.079(7 ) ,  = 82.955(6) , v = 1841.8(3 )  , z = 2 , t = 120(2 ) k , dcalcd = 1.386 
 g cm ,  = 0.773 mm , n(unique ) = 7178 ( merged from 11316 ) , rint = 0.0750 , r1 = 0.0604 , wr2 ( all data ) = 0.1401 , gof = 1.01 , max = 0.46 e  .
 six compounds based on dipicolinic 
 acid esters have been synthesized 
 and hirshfeld surfaces used to investigate the structure - directing 
 effects of functional groups in controlling their solid - state behavior . 
 
 compounds 14 are 4-bromo dipicolinic 
 acid esters substituted with methyl , ethyl , propyl , and benzyl groups , 
 respectively . 
 the main structure - directing motif within 13 is a pairwise oh interaction 
 involving two carbonyl oxygen atoms and two aromatic h atoms . 
 the 
 introduction of bulky benzyl groups in 4 forces a significant 
 change in the position of this interaction . 
 compounds 2 and 4 were used in suzuki coupling reactions to prepare 
 extended analogues 5 and 6 , respectively , 
 and their solid - state behavior was also studied using hirshfeld surfaces . 
 
 extension of these dipicolinic acid esters results in the complete 
 loss of the pairwise oh interaction in 5 , where the dominant structure - directing motifs are -based 
 interactions . 
 however , the pairwise oh interaction 
 reappears for the more flexible 6 , demonstrating control 
 of the solid - state structure of these dipicolinic acid derivatives 
 through the choice of functional groups . 
Introduction
Results and Discussion
Conclusion
Experimental Section