本文的例子是我们在研究鬼箭羽时发现的一个新化合物,当时其绝对构型采用经验规则与已知绝对构型的进行比较来确定的,发表在Natural Product Research上。后来,我们采用量化计算的方式,同样的确定了该化合物的绝对构型,下面详细的笔记,与诸位分享。Gaussian模拟溶剂下的ECD光谱

该化合物的英文名我们定为catechin lactone A (CLA),其化学结构和甲醇中实测CD光谱如下:

CLA的结构和CD光谱(甲醇)

CLA的2,3位为手性中心,通过它们在氢谱中的耦合常数,可知2,3位的两个氢处于对位,因此CLA可能为(2R,3S)和(2S,3R)两种绝对构型。下面详细说明具体的步骤:

1. 首先在gaussview中将构建CLA的3D分子模型,并对其结构进行优化。

这个化合物有两个手性中心,分别为图中箭头所指的位置。事先已经得知OH和Ar的朝向相反,所以若连接Ar的手性碳为S构型,则连接OH的手性碳为R,称为情况1.若连接Ar的手性碳为R构型,则连接OH的手性碳为S构型,称为情况2.

在情况1下,构建的输入文件如下:
%nprocshared=16
%mem=32GB
%chk=/home/xs/yjh/cdtry2-1C.chk
# opt freq b3lyp/6-31g(d) scrf=(solvent=methanol)

[No Title]

0 1
 C                 -5.55628238   -1.31201768    0.41502838
 C                 -5.49337448   -2.68989041    0.66771390
 C                 -4.26766705   -3.36415459    0.60073789
 C                 -3.09945710   -2.66258202    0.28120647
 C                 -3.13176688   -1.26596279    0.14496384
 C                 -4.36150486   -0.59503739    0.20799081
 C                 -1.78779957   -3.42132119    0.06524691
 C                 -0.60584820   -2.48940164    0.34186691
 C                 -0.79125907   -1.23039583   -0.51813155
 O                 -1.92754854   -0.49268059   -0.03099656
 C                 -4.39446030    0.92949183    0.07457510
 C                 -3.23488067    1.65664195   -0.22206940
 C                 -3.28962707    3.05618841   -0.28271823
 C                 -4.50192220    3.71953238   -0.04168854
 C                 -5.65965114    2.98056177    0.24103719
 C                 -5.59961760    1.58146545    0.27783860
 O                 -6.85529518   -0.68189906    0.36430910
 O                 -4.21166207   -4.77166494    0.84711722
 O                  0.60690589   -3.16358866   -0.00397741
 C                  0.45578307   -0.33296230   -0.41278679
 C                  0.82247778    0.48633577   -1.48902081
 C                  1.95726104    1.30305033   -1.39304324
 C                  2.72538924    1.30037579   -0.22093011
 C                  2.35872770    0.48108566    0.85525942
 C                  1.22393132   -0.33559747    0.75935590
 O                  3.88338530    2.13368389   -0.12309114
 O                  2.33143775    2.13918630   -2.49114241
 C                 -6.85745230    0.74511248    0.55131655
 O                 -2.11109688    3.80653057   -0.58766669
 O                 -4.55731531    5.14779257   -0.08560301
 O                 -7.91114496    1.31777015    0.93254772
 H                 -6.38644560   -3.22981737    0.90394351
 H                 -1.74041869   -4.27570438    0.70763311
 H                 -1.74454076   -3.73940199   -0.95547319
 H                 -0.57132605   -2.20966978    1.37407495
 H                 -0.93686365   -1.51839788   -1.53829856
 H                 -2.31102127    1.14659716   -0.39885433
 H                 -6.58600125    3.48335631    0.42524492
 H                 -3.49551023   -5.15753079    0.33735143
 H                  1.35305317   -2.57983490    0.15130380
 H                  0.23604138    0.48831139   -2.38399703
 H                  2.94521767    0.47909963    1.75018541
 H                  0.94400497   -0.96116465    1.58107971
 H                  4.52697928    1.72039032    0.45711910
 H                  3.28440708    2.25496928   -2.49499921
 H                 -2.15682246    4.66330899   -0.15696865
 H                 -5.23756687    5.46029692    0.51540498
优化结果如下:

comform1
显示没有虚频。

对于情况2,构建的输入文件如下:
%nprocshared=16
%mem=32GB
%chk=/home/xs/yjh/cdtry2-2C.chk
# opt freq b3lyp/6-31g(d) scrf=(solvent=methanol) geom=connectivity

[No Title]

0 1
 C                  1.96153200    2.04911400   -0.68088800
 C                  1.24956400    3.22899400   -0.85887800
 C                 -0.03616800    3.31847700   -0.34459600
 C                 -0.62178700    2.23979000    0.34306100
 C                  0.11800100    1.06107900    0.48424000
 C                  1.44490700    0.91943500   -0.01243900
 C                 -2.00876700    2.36236400    0.93457000
 C                 -2.24597300    1.30728000    2.00915700
 C                 -1.79295800   -0.06621900    1.48367000
 O                 -0.40900700   -0.03228300    1.12024800
 C                  2.30851000   -0.26399000    0.10246000
 C                  1.95830100   -1.46718700    0.75073800
 C                  2.84228100   -2.53479000    0.81155200
 C                  4.12082200   -2.44372200    0.22250000
 C                  4.49024500   -1.28035100   -0.41525200
 C                  3.59939000   -0.19452800   -0.47909400
 O                  3.21971000    2.06973900   -1.22680600
 O                 -0.69722600    4.49555100   -0.54221000
 O                 -1.49404300    1.70223200    3.14697400
 C                 -2.67552100   -0.60522000    0.36571100
 C                 -4.01762100   -0.90358700    0.65298100
 C                 -4.86311200   -1.39840400   -0.33269000
 C                 -4.36515400   -1.60648600   -1.63168900
 C                 -3.03652500   -1.32570500   -1.92005700
 C                 -2.18946400   -0.82814800   -0.92331300
 O                 -5.28297900   -2.09887400   -2.53182700
 O                 -6.16214600   -1.68364700   -0.03663600
 C                  4.08404100    1.00064000   -1.17177200
 O                  2.46983900   -3.67721100    1.44653800
 O                  4.90268600   -3.56880200    0.34999300
 O                  5.17093300    1.12642600   -1.69394900
 H                  1.69757500    4.06044900   -1.38856800
 H                 -2.14357100    3.34041500    1.41701700
 H                 -2.78560500    2.26258600    0.16395800
 H                 -3.31847500    1.25624200    2.24630200
 H                 -1.81798800   -0.77818700    2.32023600
 H                  0.99523000   -1.58752200    1.21898500
 H                  5.46626100   -1.16770400   -0.87910500
 H                 -1.58275100    4.44227100   -0.15286500
 H                 -1.51644400    0.98227700    3.79708000
 H                 -4.42794600   -0.76997800    1.65024700
 H                 -2.65268300   -1.49813900   -2.92376100
 H                 -1.15098900   -0.63053000   -1.15851700
 H                 -4.85524000   -2.24543700   -3.38885000
 H                 -6.57687400   -2.03039500   -0.84536900
 H                  3.21555000   -4.30002200    1.39055800
 H                  5.76455000   -3.41436700   -0.06578900

结果显示:

conform2
显示没有虚频

2. 然后,我们会对优化完的化合物进行ECD的模拟,我们采用的是TD-SCF的方法来模拟ECD光谱。

对于情况1:
输入文件如下,其中Nstates=M代表计算M个电子态,Root=N,指定感兴趣的态计算广义密度(通俗点,就是优化第N个激发态)。默认是第一激发态(N=1)。而Symm=Loose代表对对称性要求很宽松,大分子经常有多个低频振动模式,因此用 DFT 对其进行优化时,使用精密的 DFT 积分网格(Int=UltraFine)往往会更可靠。
%nprocshared=16
%mem=32GB
%chk=/home/xs/yjh/cdtry2-1C-sTD311r19.chk
#p TD=(Nstates=19,Root=19) B3LYP/6-311g(d,p)  scrf=(solvent=methanol) SCF=Tight Symm=Loose Int=UltraFine

[No Title]

0 1
 C                 -3.09104200    1.53663300    0.02701200
 C                 -3.04328600    2.92488500    0.03403500
 C                 -1.80361300    3.55167300    0.00485500
 C                 -0.61165600    2.80330200   -0.04205100
 C                 -0.70232400    1.40589600   -0.01937000
 C                 -1.94811600    0.71367200    0.01002600
 C                  0.72561700    3.50792100   -0.13955400
 C                  1.85317000    2.54659000   -0.49594300
 C                  1.68103300    1.24913900    0.31477000
 O                  0.42658900    0.63611600   -0.04853800
 C                 -2.14898700   -0.74075200    0.03176400
 C                 -1.11586000   -1.70095700    0.03070500
 C                 -1.39798800   -3.05958700    0.05449100
 C                 -2.73294900   -3.52324900    0.07809400
 C                 -3.76155100   -2.60620300    0.07919900
 C                 -3.48279400   -1.22583600    0.05718600
 O                 -4.36533600    1.01909100    0.05137100
 O                 -1.80721200    4.91387300    0.00910000
 O                  3.07633100    3.19614000   -0.18624400
 C                  2.78191300    0.24602100    0.06414800
 C                  3.86185500    0.17234100    0.95713000
 C                  4.92141000   -0.69700000    0.71442600
 C                  4.90732600   -1.51132600   -0.43288500
 C                  3.83811000   -1.44361300   -1.32147900
 C                  2.78122100   -0.56179400   -1.07878800
 O                  5.99482800   -2.33449900   -0.57136000
 O                  5.96411000   -0.76128000    1.59288000
 C                 -4.63134800   -0.32701900    0.06310400
 O                 -0.37482900   -3.95203000    0.05392500
 O                 -2.87027400   -4.88440800    0.09797900
 O                 -5.80413300   -0.65816300    0.07916200
 H                 -3.95896000    3.50314700    0.06209700
 H                  0.69135500    4.30232900   -0.89719700
 H                  0.98911600    3.98727800    0.81450700
 H                  1.80336000    2.28428600   -1.56317600
 H                  1.64719200    1.51118500    1.38074100
 H                 -0.07988800   -1.40223100    0.01321400
 H                 -4.79819600   -2.92713000    0.09748800
 H                 -0.89989700    5.25573500    0.04608000
 H                  3.79922600    2.60973500   -0.46578700
 H                  3.88677000    0.78245400    1.85554500
 H                  3.83190400   -2.07847900   -2.20412000
 H                  1.95067700   -0.51741300   -1.77527000
 H                  5.91087300   -2.86962400   -1.37681700
 H                  6.59210300   -1.42562600    1.25737300
 H                 -0.75771600   -4.84803200    0.07281700
 H                 -3.80935600   -5.13074600    0.11104700
运行的结果用gausssum读取,选择波长210~400nm,sigm=0.34
ECD1

对比上面的实测CD图谱,显然不是此构型。
对于情况2:
输入文件如下:
%nprocshared=16
%mem=32GB
%chk=/home/xs/yjh/cdtry2-2C-s311TDr19.chk
#p TD=(Nstates=19,Root=19) B3LYP/6-311g(d,p)  scrf=(solvent=methanol) SCF=Tight Symm=Loose Int=UltraFine

[No Title]

0 1
 C                  2.02941600    2.03592800   -0.66065800
 C                  1.34821400    3.23218800   -0.84363100
 C                  0.05040800    3.34216200   -0.35832100
 C                 -0.57011000    2.26987800    0.30864100
 C                  0.14105700    1.07269500    0.45222300
 C                  1.47762000    0.90958500   -0.01937500
 C                 -1.96533200    2.41055400    0.87658100
 C                 -2.22330000    1.37200700    1.96197500
 C                 -1.80052500   -0.01762300    1.45473100
 O                 -0.41510400   -0.01184800    1.06670900
 C                  2.31339600   -0.29226200    0.09561300
 C                  1.91905200   -1.49758600    0.71334000
 C                  2.77579900   -2.58729500    0.77715800
 C                  4.07395800   -2.52271000    0.22247100
 C                  4.48654100   -1.35631100   -0.38457300
 C                  3.62241500   -0.24608100   -0.45210600
 O                  3.30600900    2.03322000   -1.17459300
 O                 -0.57706400    4.53508400   -0.55928700
 O                 -1.45862500    1.75386200    3.10058300
 C                 -2.70031900   -0.56160500    0.35449400
 C                 -4.02859800   -0.88545600    0.67964100
 C                 -4.89452700   -1.38198900   -0.28731000
 C                 -4.43733800   -1.56887000   -1.60588600
 C                 -3.12173900   -1.26201200   -1.93111500
 C                 -2.25355200   -0.76144100   -0.95294300
 O                 -5.37342600   -2.06513200   -2.47770100
 O                 -6.18166700   -1.69381400    0.04553200
 C                  4.14242500    0.94794900   -1.10851700
 O                  2.35696100   -3.72860100    1.38175400
 O                  4.81389900   -3.66646300    0.35215100
 O                  5.24958200    1.07242200   -1.60287200
 H                  1.82342400    4.05954000   -1.35669400
 H                 -2.10438600    3.39830200    1.33411600
 H                 -2.72779900    2.30365200    0.09420600
 H                 -3.29373900    1.34691800    2.20205700
 H                 -1.82145100   -0.71246900    2.30229300
 H                  0.93996100   -1.60085700    1.15234200
 H                  5.47812700   -1.27122100   -0.81792500
 H                 -1.49200700    4.49211000   -0.23919900
 H                 -1.65216600    1.12706400    3.81686600
 H                 -4.40572700   -0.76698600    1.69194700
 H                 -2.76786400   -1.41656900   -2.94753000
 H                 -1.22706800   -0.54302500   -1.22232100
 H                 -4.98014600   -2.19294000   -3.35585500
 H                 -6.61763800   -2.03661700   -0.75488500
 H                  3.08333500   -4.37671100    1.33573300
 H                  5.69084000   -3.55025000   -0.04795300

结果用gausssum查看,选择波长210~400nm,sigm=0.34结果如下:
ECD2

对比实测图谱,发现所有峰形轮廓基本吻合,在260nm左右都具有最突出的峰。证明化合物连接Ar的手性碳为R构型,则连接OH的手性碳为S构型(即我们文章中报道的(2R, 3S)构型

在做ECD模拟的时候,要采用多种基组6-31G(d),6-311(d,p)等,要摸索Nstate和Root的具体数值,还要在gausssum中查看时,改变sigma等参数,直到找到与实验结果最吻合的图谱。